Patients’ Lived Experiences During the Transplant and Cellular Therapy Journey: Harvest and Hope 3031256018, 9783031256011

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Jean Coffey John M. Hill Jr. Thomas Long Elizabeth B. McGrath Editors

Patients’ Lived Experiences During the Transplant and Cellular Therapy Journey Harvest and Hope

Patients’ Lived Experiences During the Transplant and Cellular Therapy Journey

Jean Coffey  •  John M. Hill Jr. Thomas Long  •  Elizabeth B. McGrath Editors

Patients’ Lived Experiences During the Transplant and Cellular Therapy Journey Harvest and Hope

Editors Jean Coffey School of Nursing University of Connecticut Storrs, CT, USA

John M. Hill Jr. Dartmouth Health Dartmouth–Hitchcock Medical Center Lebanon, NH, USA

Thomas Long School Nursing University of Connecticut Storrs, CT, USA

Elizabeth B. McGrath Dartmouth Health Dartmouth–Hitchcock Medical Center Lebanon, NH, USA

ISBN 978-3-031-25601-1    ISBN 978-3-031-25602-8 (eBook) https://doi.org/10.1007/978-3-031-25602-8 © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 This work is subject to copyright. All rights are solely and exclusively licensed by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland

The DAISY Foundation was created in 1999 following the death of 33-year-old J. Patrick Barnes. His family was deeply touched by the care of his hospital nurses and established DAISY to express their gratitude through The DAISY Award for Extraordinary Nurses. In addition to this, now meaningful international recognition program for nurses, the Foundation funds nursing research and evidence-based practice projects in which clinicians play a significant role. DAISY is very proud to have provided a grant to this outstanding team of nurses! Together, these nurses are making care better for patients and families. Bonnie Barnes, FAAN Doctor of Humane Letters (h.c) Co-founder, The DAISY Foundation [email protected]

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 The DancerChristine HendersonAcrylic“Life isn’t about waiting for the storm to pass, it’s about learning to dance in the rain.” – Vivian Greene Throughout my time as the Creative Visual Artist, I have seen artists bloom and find inner strength as well as passion for a new life direction. The diagnosis of cancer is life changing. The holistic approach of art brings beauty, healing, and hope.

This book is dedicated to all of our patients and their care partners who shared their personal stories for this endearing project. To all the artists and poets who contributed their fine work. To all of the expert and compassionate nurses and providers who care for these exceptional people. And to our dear friend, colleague, nurse extraordinaire, Claire Robitzer RN, a true leader in transplant and cellular therapy (TCT) nursing.

Foreword

In 1989, after being diagnosed with acute myeloid leukemia, I underwent an autologous bone marrow transplant. In those pre-internet days, patient education consisted solely of a verbal description of the procedure from the transplant physician and an excruciatingly detailed recitation of potential risks and outcomes after transplant. Fifteen minutes into the doctor’s presentation, I was so confused and overwhelmed I only processed bits and pieces of the information he subsequently presented and left the meeting terrified and definitely not “educated” in the true sense of the word. I also felt so alone. Frankly, I didn’t recall what bone marrow was or why it was important, let alone know others who had been through a bone marrow transplant. Although I agreed to go through with the transplant, I was filled with dread about the potential side effects and how it would affect my life afterward, assuming I survived. Hematopoietic cell transplantation (HCT) was, and continues to be, a complex, confusing science for both patients and clinicians who have little experience with the procedure. The intensity of the therapy, the practical and emotional challenges for patients who need to find suitable stem cell donors before proceeding to transplant, and the significant short- and long-term impact of the pre-transplant conditioning regimen make it unique. The transplant impact on the physical, emotional, mental, and financial health of both the patient and his/her family distinguishes HCT from other cancer therapies with which many are familiar. For healthcare professionals (HCPs), it is important to understand the science, procedural steps, and the management of side effects that can arise during and after HCT. It is equally important, however, that they also understand the HCT experience from the patient’s perspective. Patients are so much more than a warm body with a disease that needs to be cured. They have personal goals that may be altered irreparably by the HCT experience. They have families whose lives are upended before, during, and after HCT due to issues like: the need to relocate for treatment, lengthy hospitalizations and follow-up care, loss of income, subsequent financial challenges, and the emotional trauma of not knowing whether a loved one will be cured, or at least survive. If they survive, they do not know whether they will be reasonably healthy, emotionally intact, and able to resume life as they once knew it. What I found most comforting, when I underwent my transplant, was having the nursing staff anticipate both the physical and emotional challenges I faced, ix

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Foreword

educating me in advance that they would occur, and responding appropriately when I needed additional psychosocial support. Understanding me as a person, rather than just a patient, meant the world to me and made a difficult 13-week hospitalization with a myriad of post-transplant complications more bearable. It is with my own experience in mind, and similar experiences related to me by patients and their family caregivers during my 30+ years as Executive Director of the patient advocacy organization, BMT InfoNet, that I read Harvest and Hope: Patients’ Lived Experiences During the Transplant and Cellular Therapy Journey. What a beautiful marriage of practical nursing training with the lived experiences of a variety of patients and family members whose lives were touched by transplant. The care that went into selecting patient experiences to share in this book, and the inclusion of family caregivers’ insights in the chapters, as well, makes this not only a rich educational guide for HCPs, but for patients and their loved ones. No two HCT patient experiences are identical, but those shared in the book can help prospective HCT patients appreciate that many others have shared similar fears, uncertainty, and challenges as they navigated the HCT experience, and make them feel less isolated and alone. Kudos to the authors for developing this worthwhile educational guide! It is well worth reading and sharing with clinicians and patients alike. Founder and Executive Director, Blood and Marrow Transplant Information Network (BMT InfoNet) Highland Park, IL, USA October, 2022

Susan K. Stewart,

Ode to a Nurse

Blair Brooks Taken down by a new cancer diagnosis –Wall all seems lost. Life as I know it – gone. Even in the initial chaos, you infuse hope and care – real care. You see the fear. You see the eroded confidence. You see the threatened will. You see it all and embrace it, embrace me. You know what I can eat and get me a smoothie. You push me to get out of bed even though I don’t want to. You clean my embarrassing mess as if it is normal. You smile and are patient. Sometimes, you stop to hold my hand. You anticipate what is coming and take time to sit with me. You share what will help get me through and you are right. 2 am. The worst time. You help get me to the bathroom when I am too unsteady and sure I am never going to get better. You assure me this won’t last. I feel just a little stronger thinking that I will be someday. You told me so.

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I share my life with you and discover you have a life too. Sometimes a very difficult story – You and your family have been through this too. You laugh at my jokes. You listen to my poems. You have no time but you stay with me anyway. You hold my wife’s hand when she needs it. You greet my kids with warmth and familiarity – so comforting for them and for my friends too. Sometimes you confront me for safety or therapy. You can be tough, kindly tough – oh that old bed alarm I hated. I really didn’t like you for a night. Shame on me, you were just doing your job. The next night we worked it out. You got me a new bed Mine was broken and bruised my ribs. You ran the request all the way to the top. You followed through just for me. You see me in the hospital or in the infusion suite. Sick, scared, recovering, sometimes rebelling. You see so many like me I know, because I did too, before this. Maybe I can give something back to you though I’m not sure how to do you justice. You made me feel worth it. I hope I…we make you feel worth it. My hat goes off my bald or curly haired head to you. You are what makes surviving the assault of disease and treatment possible. We could not do this without you. Thank you.

Ode to a Nurse

Ode to a Nurse

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ODE TO A NURSE Blair Brooks Taken down by a new cancer diagnosis –Wall all seems lost. Life as I know it – gone. Even in the initial chaos, you infuse hope and care – real care.

I share my life with you and discover you have a life too. Sometimes a very difficult story – You and your family have been through this too.

You see the fear. You see the eroded confidence. You see the threatened will. You see it all and embrace it, embrace me.

You laugh at my jokes. You listen to my poems. You have no time but you stay with me anyway.

You know what I can eat and get me a smoothie. You push me to get out of bed even though I don’t want to.

You hold my wife’s hand when she needs it. You greet my kids with warmth and familiarity – so comforting for them and for my friends too.

You clean my embarrassing mess as if it is normal. You smile and are patient. Sometimes, you stop to hold my hand.

Sometimes you confront me for safety or therapy. You can be tough, kindly tough – oh that old bed alarm I hated.

You anticipate what is coming and take time to sit with me. You share what will help get me through and you are right.

I really didn’t like you for a night. Shame on me, you were just doing your job. The next night we worked it out.

2 am. The worst time. You help get me to the bathroom when I am too unsteady and sure I am never going to get better.

You got me a new bed Mine was broken and bruised my ribs. You ran the request all the way to the top. You followed through just for me.

You assure me this won’t last. I feel just a little stronger thinking that I will be someday. You told me so.

You see me in the hospital or in the infusion suite. Sick, scared, recovering, sometimes rebelling. You see so many like me I know, because I did too, before this. Maybe I can give something back to you though I’m not sure how to do you justice. You made me feel worth it. I hope I…we make you feel worth it. My hat goes off my bald or curly haired head to you. You are what makes surviving the assault of disease and treatment possible. We could not do this without you. Thank you.

With permission of Brenda Trombley

Acknowledgments

We would like to thank Dartmouth Health, Dartmouth Cancer Center, Dartmouth Cancer Center’s Transplant and Cellular Therapy and Hematology team of providers, The DAISY Foundation’s J.  Patrick Barnes Grant for Nursing Research and Evidence-Based Practice Projects, UConn School of Nursing, IDea Network of Biomedical Research Excellence (INBRE) New Hampshire, Rebecca Ester Cruz RN BSN, Samantha Rossi RN BSN BMTCN, Ashley Riley RN BSN BMTCN, Molly Bennett RN BSN, Stacey D.  Aldrich RN BSN, Michael Scott Nelson RN BSN, Marv Klassen-Landis, Marianne Barthel, and Christine Henderson. With special gratitude to our colleague Lisa Wesinger, without whose vision, persistence, leadership, and professionalism you would not be holding this book in your hands.

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Contents

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Introduction������������������������������������������������������������������������������������������������   1 Lisa Wesinger

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 Creating a Patient-Centered Case Study ������������������������������������������������   9 Jennifer Holl, Lisa Wesinger, Judi Gentes, Carissa Morton, and Jean Coffey

Part I The Autologous Stem Cell Transplant Journey 3

 Hope and Determination: A Family’s Strength��������������������������������������  21 Lisa Wesinger, Carissa Morton, Judi Gentes, Jennifer Holl, and Clare Wilmot Goreau

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The Hugger ������������������������������������������������������������������������������������������������  39 Lisa Wesinger and Win Hathaway

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Spaces In-Between ������������������������������������������������������������������������������������  47 Judi Gentes and Blair Brooks

Part II The Allogeneic Stem Cell Transplant Journey 6

Saving Superman ��������������������������������������������������������������������������������������  59 Sara Cooke and Raleigh Ormerod

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Brothers in Arms����������������������������������������������������������������������������������������  71 Lisa Wesinger and Melissa Post

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Letting Go ��������������������������������������������������������������������������������������������������  81 Carissa Morton and Deb Williams

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Another Ode to August������������������������������������������������������������������������������  91 Lisa Wesinger, Amelia Lincoln, and James Patterson

10 Doctor’s Orders������������������������������������������������������������������������������������������  99 Ashley Prokopik and Tom Davis

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Contents

11 Am I Dreaming?���������������������������������������������������������������������������������������� 107 Judi Gentes and Judy Doherty 12 With  Every Sunrise I’ll Do Better������������������������������������������������������������ 117 Sara Cooke and Kathleen Skinner Shulman Part III The CAR T-Cell Journey 13 Second Chances������������������������������������������������������������������������������������������ 129 Kate Caldon and Mark Gorman Part IV Afterword 14 Saying  Goodbye, Lasting Reflections, and New Horizons �������������������� 147 John M. Hill Jr. My Wish: Liane Lambert Wind ���������������������������������������������������������������������� 155

Editors and Contributors

About the Editors Jean Coffey, PhD, APRN, CPNP, FAAN  is a Clinical Professor at the University of Connecticut School of Nursing where she teaches research across the undergraduate and graduate programs. She holds a dual appointment as professor in the UConn School of Medicine. A practicing nurse for over 40 years she is a nationally certified Pediatric Nurse Practitioner and a Fellow in the American Academy of Nursing. John M. Hill Jr., MD  is an Associate Professor of Medicine in the Geisel School of Medicine at Dartmouth and Director of the Allogeneic Transplant and Cellular Therapy Program in the Dartmouth Cancer Center at Dartmouth Health. His primary area of interest is the use of cellular immunotherapy for the treatment of patients with hematologic malignancies and in novel approaches toward minimizing morbidity and mortality and optimizing functional status following this therapy. Thomas Lawrence Long, PhD  , a medical humanities and health studies scholar, is curator of the Josephine A. Dolan Nursing History Collection at the University of Connecticut’s School of Nursing. He is the author of AIDS and American Apocalypticism: The Cultural Semiotics of an Epidemic (SUNY Press), co-author of Writing in Nursing: A Brief Guide (Oxford University Press), and co-editor of The Meaning Management Challenge: Making Sense of Health, Illness, and Disease (Brill). Elizabeth B. McGrath, DNP, AGACNP-BC, AOCNP, ACHPN  is an advanced practice nurse currently employed at Dartmouth-Hitchcock Medical Center as a nurse practitioner in the Gastrointestinal Program in the Dartmouth Cancer Center. She is the Director of the Dartmouth Cancer Center Survivorship Program and chair of the Psycho-oncology subcommittee. She has over 4 year’s oncology experience and has worked in a variety of practice settings. Elizabeth is an Assistant Professor of Medicine at the Geisel School of Medicine at Dartmouth, an Associate Professor of Nursing at Northeastern University and Adjunct Faculty for graduate nursing at Colby-Sawyer College.

About the Contributors Kate L. Caldon, RN, BAN, BMTCN  is currently employed at Dartmouth-Hitchcock Medical Center as a Transplant and Cellular Therapy (TCT) Nurse Navigator for the Blood and Marrow Transplant Program at Dartmouth Cancer Center. She began her nursing career in 2003 as an inpatient BMT nurse. She is a Bone Marrow Therapy Certified Nurse and has recently turned her focus from BMT to the emerging field of CAR T-cell therapy.

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Sara Cooke, BSN, BMTCN  has been an oncology nurse specializing in TCT for the past 7 years. She is a Bone Marrow Therapy Certified Nurse (BMTCN). She was inspired to become an oncology nurse by the staff that cared for her father when he was diagnosed with lymphoma when she was 12 years old. Judi Gentes, RN, BSN, BMTCN  has been a TCT nurse since 2013, caring for patients at the bedside undergoing peripheral blood stem cell transplant. Judi recently transitioned to the TCT nurse navigator position where she guides patients through their entire transplant journey. Jennifer  R.  Holl, DNP, RN  has been an oncology nurse for 16 years. Dr. Holl is the Nurse Educator for the Dartmouth Cancer Center. Her primary area of academic interest is utilizing health-related quality of life data to improve patient-provider communication and symptom management for patients undergoing chemotherapy and biotherapy treatment. Carissa Morton, RN, BSN, OCN, BMTCN  began her nursing career in the oncology special care unit. She is nationally certified in Bone Marrow Transplant and Oncology nursing. Currently, she splits her time between the outpatient oncology clinic and inpatient unit. She maintains a presence at the bedside, working with stem cell transplant, cellular therapy, and hematology patients; her heart has a special place for this patient population. Maybe this is because while she was in nursing school, she spent a few weeks in that exact unit during her own autologous stem cell transplant for Hodgkin Lymphoma. Ashley Prokopik, RN, BSN, OCN  started her journey with oncology during nursing school as an intern in the summer INBRE (Idea Networks of Biomedical Research) program. She was paired with the oncology nurses creating the innovative case studies. After graduation, she went on to become part of the inpatient nursing team completing chemotherapy/biotherapy administration training and obtaining oncology nurse certification. She currently works with oncology patients in the ambulatory clinic. Lisa Wesinger, RN, BSN, OCN, BMTCN  has been a TCT nurse since 1998. She spent the first 20 years at the bedside caring for this complex patient population and recently joined the TCT Nurse Navigator team guiding patients throughout their entire transplant experience. She maintains both her Oncology Nurse Certification and Blood and Marrow Transplant Nursing Certification.

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Introduction Lisa Wesinger

“Continuous effort – not strength or intelligence – is the key to unlocking our potential.” ―Winston S. Churchill

For the last 24 years of my nursing career, I have been blessed and honored to primarily care for the vulnerable patient population of transplant and cellular therapy (TCT). I’ve often compared the difficult journey of an individual undergoing TCT to that of a soldier at war. A person goes about their life, something changes, something is different, and then all of sudden they are diagnosed with a new life-­ threatening hematological disease and the long battle to survive begins. Battles aren’t won by an individual alone – you need a platoon – you need trust – you need to know that your platoon has your back. The TCT team of physicians and nurses work hard to build trusting relationships with the patient and their families in an effort to make the best plan possible to achieve a long remission or cure. These relationships can last months to years. Bedside nurses often meet the patient upon diagnosis; they quickly work to build trust as they cheer the patient through their ultimate journey to a new healthy life. We utilize our expertise in TCT to administer chemotherapy, manage side effects, infuse stem cells or CAR T-cells, hold their hands through the tough times, and push them out of bed to walk and stay strong. We sit with their loved ones to assure them that everything will be okay – have hope – as long as you have hope we will keep pushing. We look forward to their post-transplant clinic appointments when they swing by the unit to say hello and fear the day when they may be readmitted due to

L. Wesinger (*) Transplant and Cellular Therapy, Dartmouth Health, Lebanon, NH, USA © The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 J. Coffey et al. (eds.), Patients’ Lived Experiences During the Transplant and Cellular Therapy Journey, https://doi.org/10.1007/978-3-031-25602-8_1

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L. Wesinger

post-transplant complications. There are very few areas of nursing in which these long-lasting relationships endure. Over the years, other practitioners have asked me, “how do you know so much about your patients?” – my response is always, “I listen.” According to Koloroutis (2004), In Relationship Based Care, the care provider–patient relationship is one in which the care provider consistently maintains the patient and family as his or her central focus. The care provider knows that each person’s unique life story determines how he or she will experience an illness. The care provider conveys an unwavering respect and personal concern for the patient, strives to understand what is most important to this particular patient and family, safeguards their dignity and well-being, and actively engages them in all aspects of the patient’s care. Almost 7 years ago, one of our nursing supervisors asked me to create a “simple” case study on hematopoietic stem cell transplant (HSCT) to educate new oncology nurses who were training in HSCT. I spent about 4 weeks outlining a case study and quickly realized that there is nothing simple about stem cell transplant. Three of my colleagues, Jennifer Holl, Carissa Morton, and Judi Gentes, who were also bedside HSCT nurses, joined me on this project. In January 2016, we started meeting weekly to develop the first case study, Hope and Determination. We met on our own time, while working full-time, caring for our children and families, caring for ill/elderly parents, family businesses, and pursuing higher education. We had a unique idea – write the case study from a medical perspective but with the patients’ and carepartners’ lived experiences embedded in the story. Judi Gentes: I was eager and excited to join this project of creating case studies with the patients’ lived experiences embedded in the story. I have a personal story to share of how I became a transplant and cellular therapy nurse. Unfortunately, my oldest son’s best friend, Alec, had been diagnosed with CLL, he was only 29 years old, he was going to need an allogeneic stem cell transplant. My son and Alec have been very close friends since the fourth grade. He spent a lot of time with our family. I was working in the same medical center in the neurology unit when he was diagnosed. I would go visit him in the transplant and cellular therapy unit after work, often this would be 7:30 at night, he was there for four weeks. I was always greeted with kindness by the nurses. They were very caring and focused on balancing the physical and emotional challenges of therapy that he faced every day. They would kindly remind me every time I was leaving for the night “we are hiring,” I would turn around and smile, secretly I was thinking this seems like a great unit, a hidden gem in this medical center. Ten years have passed and I am ever so grateful and honored to have joined the transplant and cellular unit. To have the opportunity to care for this very frail and vulnerable patient population. I am a second career nurse. I entered the nursing field to have a more meaningful career, to have the opportunity to be part of something bigger, being part of this project more than filled that desire. Carissa Morton: Yes! This was my answer when I was approached by Lisa to join a project where we were going to make a case study to help educate nurses new to HSCT. We met to discuss how we would start this process. We could have easily made-up data, lab values, and scenarios but we wanted to do better than a fictitious story. That is when we came up with Hope—my story is Hope and Determination. Six years prior to our project I was a terrified young woman with newly diagnosed Hodgkin lymphoma. I was fighting to live while still trying to push forward with my life. You will read more of my journey in that chapter.

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This project grew throughout the years from the simple case study; to interviewing and writing case studies for our other participants; and finally, to this book. As the project progressed over the last almost seven years our group has grown in members as well as in our work and personal lives. I was pregnant with my first child when we started—I now have a second. I changed nursing positions to a part time position at an outpatient oncology clinic within the same medical center closer to home to allow me to spend time with my small children. I maintain my per diem status on the TCT unit though because I couldn’t bring myself to step away completely. The patients we meet and care for are very special and make as much of an impact on our lives as we do on theirs. As a group we have stuck it out through many changes and hurdles. I am thankful we were able to share these patients’ and carepartners’ journeys. I hope these stories make an impact on readers whether they are nurses or other health care providers as well as patients and family members who have had or are working toward HSCT or CAR-T treatments.

We were very fortunate to have been mentored by one of our nursing leaders, Dr. Jean Coffey, who at that time was the Director of Nursing Research and Education, at the institution we all worked. With Jean’s guidance, we created a Case Study Methodology that we used to write our first story, Hope and Determination, and later developed our qualitative interpretative phenomenological analysis (IPA) nursing research project. Jean Coffey: I took a phone call one day from Lisa who asked me to help them with their case study. I met Lisa, Judi, and Carissa a few days later. I realized I had met three nurses determined to create a case study to serve the patients for whom they cared. The journey to this book is nothing short of amazing. Lisa gathered more bedside nurses as well as a transplant MD, Oncology NP, and a medical humanities and health studies scholar to assure the project would be successful. We met on a regular basis over the next several years as the project emerged from a presentation to a manuscript to a book. I have been so humbled to work with this dedicated team who used their personal time to create this book. I hope more bedside nurses will follow their lead and know that they have much to contribute to the literature, making care better for their patients.

We presented “Hope and Determination” in October 2016 to a live audience of nursing leaders, colleagues, and nursing students. This presentation was very unique. The four nurse writers each presented the HSCT medical portion while the voice of the patient, embedded into the PowerPoint, told the lived experience of her journey. We realized immediately that the voice of the patient connected to the audience in a powerful manner. There was not a dry eye in the auditorium. In the spring of 2017, Dr. Thomas Long, Professor in Residence at the UConn School of Nursing, was at our institution leading a nursing writing workshop. Dr. Coffey arranged for the four nurses to meet with Dr. Long to discuss our project. He enthusiastically told us that this was “groundbreaking” work and that he would be happy to consult on our project. Thomas Lawrence Long: During my tenure providing writing support services in the UConn School of Nursing, I occasionally was invited to give workshops to nurses and other healthcare providers (e.g., Connecticut Children’s Medical Center, the University of Texas Arlington College of Nursing and Health Innovation), but none has given me such a sustained sense of admiration and satisfaction as this project. Nursing faculty in clinical assignments are expected to publish scholarship but find it difficult to juggle this activity

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L. Wesinger with their teaching and clinical practice. That full-time nurses and a physician would bring persistent effort over years of work to the writing of these case studies and their publication is a testimony to their dedication to bringing patients’, caregivers’ and their own lived experiences to a wider audience. It bespeaks an inexhaustible sense of mission, even more admirable for having been conducted during the COVID epidemic. Moreover, they invented a new type of case study, one in which the patients’ and caregivers’ voices are woven through the professionals’ technical narratives. When I inquired of the International Academy of Nurse Editors whether this kind of innovative method had been published in their journals, they told me it had not. So these health care professionals and Springer are breaking new ground that we hope will be replicated by others in the future.

In the summer of 2017, Ashley Prokopik was a nursing school junior who participated in an Idea Networks Biomedical Research Excellence (INBRE) program. The INBRE program provides the student a hands-on, experiential research opportunity and professional/research-related training. Ashley was assigned to our research team and was instrumental in helping us obtain Institutional Review Board (IRB) approval to move forward with our IPA nursing research project. Ashley Prokopik: My journey with this research team started before I completed my bachelors in Nursing. I was approached for an opportunity to complete research in conjunction with Dartmouth College and nurses employed at Dartmouth-Hitchcock. The Idea Networks of Biomedical Research Excellence (INBRE) utilizes research institutions and undergraduate facilities to promote evidence-based practice research through science and technology research. Upon being selected for this program, I was matched with Lisa Wesinger. It was history from there; we worked tirelessly to achieve institutional review board approval, develop interview resources, research our method, and extrapolate themes for our case studies. As someone who was prior convinced she would go into intensive care, I rapidly fell in love with the oncology patient population. I completed my nurse residency with the University of New Hampshire at Dartmouth-Hitchcock and continue as an oncology nurse today. I currently hold my Oncology Certified Nurse certification and have developed many long-lasting relationships with many patients and their caregivers. This research has changed the way I view nursing care and nursing research. As the youngest member of the team and just starting out as a student back in the day, I was immersed in the world of research and oncology and learned not only about the bone marrow transplant protocols and CAR-T, but about the patients themselves and what they value. I learned the value of the caregiver. It led me to lead the nurse-led research practice council at my current clinic, and I greatly value the “why?” question of nursing. Everything is done for a reason, and I enjoy finding the reason why! I’m known on the team for being the technology go-to. I personally hand transcribed every interview and from this feel a deep seated connection to our case studies. I had the privilege of spending hundreds of hours listening to these individuals and their amazing journeys. As a nurse, I think it is critical to take this time to speak to patients in a personal way and learn their story. From working with this patient population, I truly have learned to value my time with my loved ones in a way deeper than I ever could have otherwise. I’m forever grateful to have been granted this time and opportunity.

With IRB approval in hand, we started interviewing the patients and carepartners. Each person was selected by their disease, TCT protocol, and their interest in telling their stories. The 11 patients received their transplant or cellular therapy between 2010 and 2020. We reached out to The DAISY Foundation and applied for a grant to help pay someone to transcribe the many hours of interviews. In 2018, our team was attending the International TCT Tandem meetings in Tampa, FL, when we

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received the email from The DAISY Foundation  – the grant was awarded  – we could proceed with the transcriptions. Dr. Coffey transitioned to a new role in nursing academics at a university/undergraduate program but stayed on as the main nursing principle investigator (PI) on the research study. It was important to the team to have a local PI with expertise in TCT. Dr. John M. Hill, the Director of Allogeneic Blood and Marrow Transplant at our institution, graciously accepted this invitation. John M. Hill Jr.: When I became aware of this project and the educational implications for transplant nurses, I immediately envisioned the opportunity for extension of these didactic benefits to other clinicians, as well, namely medical students, housestaff, fellows, junior attendings, and even some of the more seasoned transplanters, including myself, not to mention Palliative Care consultants, Social Work staff, and other ancillary colleagues. The point here is that we have been so ingrained in the “third person” case history method of medical teaching over the years that the “first person “perspective of the patient and care partner has been largely underappreciated, except in those instances where we specifically inquire about the patient‘s experience, or they choose to volunteer that insight. Such an opportunity to glean this invaluable perspective was, therefore, too important not to embrace, and I was “all in.” Furthermore, once we began to carry out these interviews, the feedback from both patients and care partners was astounding, alluding to the emotional release and almost “cathartic” benefit of this experience. It became clear that this was an essential component for many in the “survivorship” process, by allowing them to “tell my story” and in so doing, step beyond the recovery stage, regain some important identity, and “give back” to the cancer community, knowing that other patients and families undergoing the transplant experience in the future would benefit from this knowledge. It is our sincere hope that this book will, therefore, serve as a reference for many individuals, representing both sides of the cancer perspective to ultimately optimize the cellular therapy journey and outcomes.

The project kept getting bigger and bigger and we needed another nurse writer. In the winter of 2018, Sara Cooke, a TCT bedside nurse, joined our team and by late spring we started interviewing 19 patients and their carepartners. All stem cell transplant interviews were completed by the end of 2018. In 2019, as the stories were created by the bedside nurse writers, the need for expert story reviews became evident. Sara Cooke: My oncology journey began when I was 12 years old and my father was diagnosed with lymphoma. I was inspired to become an oncology nurse by the extraordinary staff that cared for him. The staff went the extra mile to help my father and the rest of my family through his treatment and survivorship. My senior year of nursing school I was paired with Lisa Wesinger in the blood and marrow transplant unit for my senior practicum. That semester cemented my desire to work in oncology and began my love of transplant and cellular therapy. I was hired into that unit as a new graduate nurse and have been there ever since. I have become a Blood and Marrow Transplant Certified Nurse and have become the primary preceptor for nurses new to transplant and cellular therapy on that unit. In the winter of 2018, Lisa was looking for someone to join the case study group. How could I say no to such an interesting project? Not only has this been an amazing group to be a part of but it has taught me a lot about the patient and caregiver experience. Watching my parents during my dad’s cancer journey, I thought I had a fair understanding of what my patients were going through. Turns out, a 12-year-old can miss quite a bit. Listening to the patients and caregivers talk about what they went through and the tough decisions they had

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L. Wesinger to make, I learned that my parents sheltered my siblings and I quite a bit during my dad’s treatment. I now have a greater appreciation for what it means to be a caregiver and what the role truly entails. This experience has made me a better, more supportive nurse.

The team approached a local APRN who specializes in hematology/oncology to help with the story reviews. Dr. Elizabeth McGrath welcomed the opportunity to join our team as our local expert nursing consultant. Elizabeth McGrath: My journey with this project has a background in being faculty for the Idea Networks of Biomedical Research Excellence (INBRE) Program at Dartmouth where I met student nurse Ashley who was working with Lisa on this research. At that time I also worked closely with Dr. Coffey in research related to the INBRE program. My background also includes working with some of the patients highlighted in this book as they graciously agreed to speak at professional meetings to help us learn about survivorship through telling their stories. I distinctly remember the audience’s response as the stories were told, the room was still and you could tell they were enthralled and awestruck, you could have heard a pin drop! Several physicians and other professionals shared with me what an incredible learning experience it was and felt they came away changed. I have had the honor of working with this incredible team for over a decade and have witnessed incredible dedication to patients, carepartners, and each other. I am humbled by the personal sacrifice of everyone in making this book possible and the courage of the patients and their loved ones.

In 2020, we treated our very first patient diagnosed with refractory Diffuse Large B Cell Lymphoma with a CAR T-cell therapy product. Kate Caldon, TCT Nurse Navigator, who was an integral part of developing the CAR T-cell program at our institution, helped navigate this patient and his carepartner through their journey and joined the team to write the final story, Second Chances. Kate Caldon: I fell in love with the modality of stem cell transplant when in college I did a paper on a theoretical inpatient Bone Marrow Transplant unit that used a shared governance model to lead and staff the unit. Around the same time, one of my favorite professors who taught psychology was diagnosed with leukemia. I always came away from his lectures with a new lesson about the power of human connection as a driving force for healing. When he became ill I was able to follow his care as he went through induction chemotherapy during my clinical rotations and it was then that I saw the power of connection outside of the classroom and at the bedside. I came away from school as a new nurse knowing I wanted to work in the field of blood and marrow transplant. I also had a sense that human connection is at the heart of what we can offer our patients and ultimately what we can offer each other in the profession of nursing and with the multidisciplinary team. When I looked for a place to start my nursing career in 2003 – I looked for these two things – a bone marrow transplant unit and a place with a strong team and a shared governance structure where I could grow. The mentoring and lessons I learned from the seasoned and experienced nurses in those early years – Lisa being one of them I have internalized. I left bedside nursing to work with the transplant program in the outpatient setting in 2011 and watched on the sidelines over the years as this amazing project evolved, the most fantastic piece, that it was driven by nurses who worked at the bedside. Seeing my longtime friend and colleague dedicate so much of herself to this work was inspiring and the excitement and passion she shared and continues to share is infectious. I was honored when she asked me to write the story of our first CAR T-cell patient. When Dartmouth started building the CAR T-cell program in 2019, I was able to be a part of it from day one and that opportunity has been exciting, challenging, and rewarding. Telling the story of our first patient was humbling as

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it is so evident that what led them to trust our center with their life was not how well researched we were on the science but was how well we were able to connect with them – across all disciplines and departments. Through this project, I learned about connection on another level and how small interactions over time create and build trust and breed courage and resilience.

An additional part of this book is art and poetry created by patients, carepartners, and staff. I realized how hard it was for patients to walk laps on our inpatient unit with nothing but blank walls to look at. We needed inspiration and beauty. So between 2016 and 2019, I worked closely with our Creative Arts Director, Marianne Barthel, Creative Visual Artist, Christine Henderson, and Creative Writer, Marv Klassen-Landis, as we collected and framed multiple pieces of art and poetry. “The Walls of Hope” was established in the inpatient unit as a gift for all to enjoy. The opening quote from Sir Winston Churchill says it all – without perseverance this project would not have come to fruition. From a simple case study to a textbook, I must say we have come a very long way.

Reference Koloroutis M, editor. Relationship-based care: a model for transforming practice. Minneapolis: Creative Health Care Management; 2004.

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Creating a Patient-Centered Case Study Jennifer Holl, Lisa Wesinger, Judi Gentes, Carissa Morton, and Jean Coffey

Case studies provide an invaluable record of professional clinical practice and have been used in medicine since the late 1800s to describe both traditional and unusual presentations of specific pathologies. In medicine, case studies traditionally take a detached, objective approach to outlining the clinical course of a disease and its treatment. The lived experience of neither the patient nor the caretaker is represented. However, in keeping with nursing’s holistic approach to patient care using the theoretical foundations established in Jean Watson’s Theory of Human Caring as well as the Relationship-Based Care Model, this research team sought to revolutionize the case study paradigm and deconstruct the traditional case study approach, placing the patient and caregiver, instead of the provider, at the center of the narrative. Consequently, this new case study method intercalates the clinicians’ analysis of the case with the patient and caregiver commentary. As a research method, case studies are used in many situations. Investigators utilize this approach when they want to understand complex social phenomena (Yin 2014). J. Holl Hematology/Oncology, Dartmouth Health, Lebanon, NH, USA e-mail: [email protected] L. Wesinger Transplant and Cellular Therapy, Dartmouth Health, Lebanon, NH, USA J. Gentes Oncology/Hematology, Dartmouth Health, Lebanon, NH, USA e-mail: [email protected] C. Morton Dartmouth Health, Dartmouth Cancer Center, St. Johnsbury, VT, USA e-mail: [email protected] J. Coffey (*) School of Nursing, University of Connecticut, Storrs, CT, USA e-mail: [email protected] © The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 J. Coffey et al. (eds.), Patients’ Lived Experiences During the Transplant and Cellular Therapy Journey, https://doi.org/10.1007/978-3-031-25602-8_2

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According to Luck et al. (2006), case studies explore, describe, or explain a phenomenon of interest by providing researchers with a holistic, meaningful understanding of real-life events. As such, case studies often employ qualitative research methodologies and are particularly useful when researchers want to answer “how” or “why” questions (Yin 2014). They can be used as a teaching tool for instructional purposes, as a form of record keeping to facilitate practice, and as a strategy to solve practical problems (Luck et al. 2006). Given their broad application, case studies have become an accepted vehicle for conducting research in a variety of disciplines (Bergen and While 2000). The unique approach to this case study method is the addition of the patient’s and caregiver’s voices. The lived experiences of a bone marrow transplant patient and caregiver’s journey are embedded within the case study format. Researchers, employing interpretive phenomenology, invited patients and caregivers to share their stories about the bone marrow transplant journey through face-to-face interviews, questionnaires, written narratives, art, poetry, and photos. Unlike other qualitative or quantitative research methods, case study research has very few requirements to follow (Meyer 2001), both a strength and limitation of this particular design. It is a strength because it allows researchers the freedom to tailor their design and data collection procedures to the phenomenon under investigation. It is a weakness, however, because the lack of clear, consistent procedures often results in the creation of poor case studies, which invites scrutiny from other researchers. The loose design of the case study, therefore, requires researchers to be very specific when making decisions about design requirements, data collection procedures, data analysis, and validity and reliability (Meyer 2001). As such, this chapter focuses on providing a comprehensive overview of the case study process from the researcher’s perspective, emphasizing methodological considerations.

2.1 Purpose and Rationale The purpose of this project was to create case studies, framed by the medical history and enhanced by the patient and caregiver voice, to educate new and currently practicing nurses, physicians, and other members of the inter-professional team caring for patients undergoing bone marrow transplant (BMT) for hematologic blood disorders and malignancies. In striving to develop a creative education strategy, the research team felt a traditional case study, woven with commentary from an actual transplant patient and their caregiver, would provide a novel and effective means of educating new and existing members of the BMT team. The initial phase of the project involved assembling the research team and choosing the phenomenon to investigate. The majority of the researchers involved in the project work as clinical nurses in the Hematology/Oncology Special Care unit of a major New England teaching hospital that specializes in the care of high acuity hematology/oncology patients as well as individuals undergoing both autologous and allogeneic BMT.

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2.2 Research Design Case studies are tailor-made for exploring processes that are poorly understood (Meyer 2001). As previously stated, the approach is particularly useful for responding to “how” and “why” questions (Yin 2014), which is exactly what the research team sought to do. The main questions under investigation were: “Why do BMT nurses carry out certain interventions when caring for patients undergoing care for hematologic blood disorders and malignancies (i.e., what is the rationale and evidence behind these interventions)?” and “How does the entire process—from the time of initial diagnosis through the trajectory of the illness—affect the patient and caregiver?” Given the limitations posed by other qualitative and quantitative research methods, the research team felt the contextual nature of a case study would provide the perfect vehicle for answering these questions. An instrumental case study design was used to create the case study. This type of case study design begins with a research question and seeks out cases that offer illumination on the topic (Polit and Beck 2014). This approach allowed the researchers to describe the phenomenon under investigation, explain the rationale behind the nursing interventions contained in the CBV protocol, and use the lived experience of an individual who had undergone this treatment to shape the narrative. To create the narrative, patients and their caregivers were interviewed and the transcripts were analyzed using Interpretive Phenomenological Analysis (IPA) (Smith et al. 2013). In this case, the phenomenon under investigation was the CBV protocols used to treat patients with lymphoma malignancies. The specific objectives were to (1) educate the BMT nurses and the inter-professional healthcare team about the process of transplant from the time of initial diagnosis through the trajectory of the disease; (2) educate the BMT nurses and the healthcare team about the potential complications associated with transplant; (3) reduce potential complications and improve outcomes for patients undergoing transplant; and (4) share the lived experience of an individual undergoing care for hematologic blood disorders and malignancies including BMT and their caregiver.

2.3 Human Subjects Approval The Dartmouth College Committee for the Protection of Human Subjects approved the project. The approval included gaining the patient expressed consent for their nurse interviewer to access individual medical records related solely to the bone marrow transplant procedure for the purpose of building the medical case. The committee also approved the recorded interviews of 19 patient and caregiver dyads with individual face-to-face engagement and follow-up questionnaires as well as participants voluntarily sharing personal photos, art, poetry, and/or journaling as they lived the experience from diagnosis through the trajectory of the disease. In some cases, the patients succumbed to their illness and the caregiver carried on the interviews to complete the case study. The team had a member of the spiritual support community present or on call in the building during all the interviews to provide emotional support to the patients and caregivers.

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2.4 Methodology 2.4.1 Case Selection According to Meyer (2001), “the logic of sampling cases is fundamentally different from statistical sampling … whereas quantitative sampling concerns itself with representativeness, qualitative sampling seeks information richness” (p.  333). Consequently, in qualitative research, cases are selected purposefully rather than randomly. Choosing to explore multiple cases from one nursing care unit created a homogeneous sample, providing the researchers the opportunity to create a rich, in-depth, detailed account of the phenomenon under investigation, which is essential when conducting this type of research. The sample of participants was purposeful as each shared a common experience of a bone marrow transplant at one healthcare institution. Typically, the sample size in IPA is small with up to 6 participants (Smith et al. 2013). This project grew to include 19 pairs of patients and caregivers who enthusiastically volunteered to share their personal reflections on the BMT journey.

2.4.2 Unit of Analysis According to Yin (2014), one way to respond to and minimize the potential for bias is to have more than one unit of analysis. Case studies can have a holistic design, which examines the global nature of the phenomenon, or an embedded design, which enables researchers to examine specific subunits (Meyer 2001). In this case, the researchers used an embedded design. They examined 12 distinct subunits: (1) diagnosis; (2) induction chemotherapy; (3) disease relapse and consolidation treatment; (4) stem cell collection and processing; (5) admission to the hospital; (6) pre-transplant conditioning with high-dose chemotherapy; (7) side effects of chemotherapy administration; (8) stem cell administration; (9) side effects of stem cell administration; (10) engraftment; (11) discharge from the hospital; and (12) post-­ transplant. These subunits told the story of the patient’s clinical medical management. However, the additional unit of analysis, the patient/ caregiver interviews, incorporated clinical understanding, differentiating between the treatment of disease (the case study outline) and the care of illness (patient and caregiver interviews) (Benner 1994).

2.4.3 Data Collection Procedures Data collection for the case studies occurred over a three-year period. This level of prolonged engagement with the phenomenon under investigation and persistent observation of patients and caregivers undergoing this procedure yielded a wealth of rich, useful information for the case studies and allowed the researchers to build a trusting rapport with the participants (Polit and Beck 2014).

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The researchers began their investigation for the case studies structure by reverse-­ engineering the existing hematologic blood disorders and malignancies/ BMT protocols. Reverse-engineering is a distinct problem-solving approach that involves taking something apart to determine how it works (Gary and Hudson 2016). Although traditionally used in engineering practices, this process of “going backward through the development cycle” (Gary and Hudson 2016, p. 83) can also be applied to nursing research and the generation of evidence-based practice. Reverse-­ engineering an existing nursing protocol requires nurses to retrieve, appraise, synthesize, and apply evidence-based practice by searching the existing nursing literature to determine if the protocol under investigation is based on the most current research evidence (Gary and Hudson 2016). As such, the team conducted an extensive search of available nursing literature to find best practices and other research evidence supporting or refuting the current nursing management of lymphoma patients undergoing transplant. These findings became the scholarly, empirical data presented in the case studies. Case studies provide researchers with opportunities of having an intimate knowledge of a person’s condition, thoughts, feelings, actions, intentions, and environment (Polit and Beck 2014). Therefore, the team engaged in a parallel process eliciting information on the lived experience of patients and caregivers as they progressed through the bone marrow transplant journey. The team used Interpretive Phenomenology (IPA) to structure the interviews and analyze the transcripts. Interviews were enhanced by participants completing a post-interview questionnaire where they could add to the information provided in the interview. The option to provide photos to the team was offered to all participants. Each one was given a flash drive where they could upload any photos they wanted to share. Some individuals also shared art and poetry they created as part of the BMT experience. Members of the team were designated as nurse interviewers and assigned a patient/caregiver dyad. They built the medical case, conducted the interviews, analyzed the transcripts, and added the voice of the dyad to the case by completing the final draft of the story, which then became a chapter in this book. The IPA method was chosen to allow both the individual and collective voices of the patients and caregivers to be heard as part of the case study. Dreyfus in Benner’s (1994) Interpretive Phenomenology states, “Those engaged in caring must be able to take on the perspective of the patient and make his or her peace with the situation and its suffering in order to be touched by the situation of a fellow human being …. Only by combining both technological and existential skills can we approach healing the embodied person” (Benner 1994, p. x). IPA is a qualitative research approach committed to the examination of how people make sense of their major life experiences. It allows for a detailed examination of the individual case and the differences and similarities between the cases while also providing context for a description of the collective experience of those with a common life experience. The value of both the individual experiences and the description of the group experience is supported by the phenomenology of Husserl, who stressed that it was important to build on the individual instances to establish the essence of an experience (Smith et al. 2013).

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2.4.4 Data Analysis The first step in the analytic process to develop the case study framework was to divide each of the 12 subunits presented in the case study among the team members so that everyone was involved in gathering evidence to support or refute the established protocol. During this phase, the emerging research data were analyzed and reanalyzed to ensure key content was included. Often, the research findings in one area led to additional questions and areas of investigation, which were then researched and incorporated where appropriate into the finished product. Once the literature was examined and all the research findings were compiled and composed, each subsection was then edited for format, content, and clarity so a consistent “voice” would emerge. The subunits were then grouped into themes (for example, diagnosis and induction chemotherapy) and presented chronologically—from the time of initial diagnosis through the trajectory of the illness—in order to document the case as it unfolded. This process reduced individual researcher bias since multiple sources were used to gather the data and more than one researcher was involved in the process of data collection, coding, and interpretation (Polit and Beck 2014). Analysis of the interviews began with a line-by-line review of transcripts from the interviews by a nurse member of the research team. Quotes and significant statements were cataloged and recorded in writing after reading and rereading the transcripts. The written analysis of each individual interview was shared with the nurse interviewers for each case who then read and reread the documents and began writing the patient story within the case study. Material from any follow-up interviews and questionnaires was included as the narrative progressed. Each nurse interviewer created the medical case for their assigned patient and caregiver and then brought in the quotes and themes from the interviews and questionnaires. For each subsection, the empirical data were presented first, followed by the patient’s experience, for maximum impact. Once the first drafts were completed, they were shared with the larger research team to read and reflect on each case. Many of the nurses and the team physician had personal knowledge of the patients and caregivers, which allowed them to include their interpretation of the account. The team of researchers continued to interact with the data in a dynamic relationship as described by Smith et al. (2013). “ Moving from the particular to the shared, and from the descriptive to the interpretive” (p. 79). They add that a key tenet of IPA is that the process of analysis is iterative: “we move back and forth through a range of different ways of thinking about the data” (Smith et al. 2013, p. 28). The team met on a regular basis and discussed the data as presented in the transcripts as well as remembering their interactions with the individuals.

2.4.5 Validity and Reliability Evaluating the quality of research is essential so findings can be incorporated into care delivery (Noble and Smith 2015). Unfortunately, qualitative research is frequently criticized for lacking scientific rigor and the findings are often dismissed as

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merely a collection of personal opinions subject to researcher bias. As such, unlike their quantitative research counterparts who apply statistical methods to establish the validity and reliability of research findings, qualitative researchers must incorporate methodological strategies to ensure the ‘trustworthiness’ of findings (Noble and Smith 2015). To safeguard the trustworthiness of findings for this case study, the research team adopted the following strategies: (1) using multiple sources of data when reverse-engineering the protocols to ensure the information presented in the case study was based on current research evidence; (2) having more than one researcher involved in the process of data collection, coding, and interpretation of findings; (3) being open-minded and receptive to new and surprising data; (4) acknowledging the limitations of using single subjects and caregivers for each case study; (5) keeping meticulous records of all major design decisions via minutes taken at every research team meeting; (6) including richly detailed verbatim descriptions of the subject’s lived experience for each of the 12 subunits analyzed; and (7) sending the finished product to an interdisciplinary review team consisting of pharmacists, physicians, and other BMT nurses to ensure the accuracy of the findings and further reduce researcher bias. In addition, auditability was met as described previously in this chapter with the sharing of the decision path of the case study process and interview procedures. Because this was an interpretive phenomenological process, bracketing was not done. Credibility is addressed by returning to some of the participants and eliciting their impressions on the findings. Detailed notes on the interview process, analysis, and team meetings are available to enhance the credibility of the study. Fittingness is addressed with direct quotes by participants sharing their lived experiences of the BMT journey.

2.5 Theoretical Underpinnings As previously stated, when used in medicine and other allied health professions, case studies traditionally take a detached, objective approach to outlining the clinical course of a disease and its treatment. Nursing, however, seeks a more holistic approach, placing the patient, not the disease, at the center of care delivery. Thus, the desire to frame the case study from the patient’s perspective has strong theoretical underpinnings. The nursing theories that most closely align with this philosophical approach include the Relationship-Based Care (RBC) model (Koloroutis 2004) and Jean Watson’s Theory of Human Caring (Watson 2008). The RBC model, developed by Creative Health Care Management, an international healthcare consulting firm, is based on the premise that “we experience the essence of care in the moment when one human being connects to another” (Koloroutis 2004, p.  4). Thus, the heart of nursing centers on the relationship between the patient and the care provider. In RBC, the nurse understands that each person’s unique life story determines how they will experience illness. Like RBC, Jean Watson’s Theory of Human Caring also emphasizes the relationship between the patient and care provider. According to Watson (2008), nurses have an

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obligation to understand the patient by inviting them to tell their story. Understanding the patient’s story requires nurses to become emotionally invested in the patient. Being emotionally invested provides powerful motivation for nurses to advocate for their patients as well as the incentive to utilize every resource to accommodate the needs of the whole person—mind, body, and spirit—to produce the best possible outcomes (Koloroutis 2004). Including the patient’s story in the case study provides authenticity. According to Polit and Beck (2014), authenticity “conveys the feeling tone of participants’ lives as they are lived” (p. 323). As such, in addition to outlining the clinical significance of the disease process and its treatment, readers of this case study are able to experience the thoughts and feelings of the subject and therefore develop a heightened understanding of the phenomenon being described. Essentially, adding the patient’s perspective to the case study enables nurses to develop the same emotional investment as individuals caring for the patient would.

2.6 Limitations Despite case studies’ suitability for many research questions, nurses have not always embraced case study research (Taylor and Thomas-Gregory 2015). This is likely because there are several ways to define case study research—each with its own design method, approach, and unique characteristics. Bergen and While (2000) argue these conflicting definitions of the term ‘case study’ result in a variety of assumptions about the robustness and trustworthiness of the method, making this form of inquiry a less attractive option when undertaking research. Even with these challenges, case study research can make a considerable contribution to nursing practice and education because it allows researchers to explore the phenomenon under investigation from a variety of perspectives to gain an in-depth, balanced picture of that experience (Taylor and Thomas-Gregory 2015). Additionally, because case studies often focus on a singular individual, group, or phenomenon under investigation, the results are not generalizable (Taylor and Thomas-Gregory 2015). This does not mean, however, that the findings are not transferable to other situations or contexts. It is the research team’s hope that by outlining the methods used to create these case studies, other nurse researchers will adopt this method and use it to describe individual experiences and a collective phenomenon of interest in their patient populations and bring more patient stories to life.

2.7 Conclusion Case studies have been used in the medical profession for over 100 years to convey the clinical course of a disease and its treatment. This form of inquiry is important to many disciplines because it allows researchers to explore a phenomenon of interest in rich detail. This chapter describes an innovative case study method whereby

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the patient’s lived experience is interlaced with their medical case study. The importance of the patient’s story is emphasized in nursing theories such as the RelationshipBased Care model and Jean Watson’s Theory of Human Caring. Despite its limitations, the researchers hope other nurses will adopt this method to investigate phenomena of interest related to their patient populations so additional patient stories can be told. Further research needs to be completed to determine if this type of case study provides an effective tool to educate nurses. We offer these patient-­ centered case studies both to inform oncology nurses and to provide an exemplar for clinical nurses in other areas of specialization.

References Bergen A, While A. A case for case studies: exploring the use of case study design in community nursing research. J Adv Nurs. 2000;31(4):926–34. Benner P. Interpretive phenomenology. Thousand Oaks: Sage Publications; 1994. Gary JC, Hudson CE.  Reverse engineering: strategy to teach evidence-based practice to online RN-to-BSN students. Nurse Educ. 2016;41(2):83–5. Koloroutis M, editor. Relationship-based care: a model for transforming practice. Minneapolis: Creative Health Care Management; 2004. Luck L, Jackson D, Usher K. Case study: a bridge across the paradigms. Nurs Inq. 2006;13(2):103–9. Meyer CB. A case in case study methodology. Field Methods. 2001;13:329–52. Noble H, Smith J.  Issues of validity and reliability in qualitative research. Evid Based Nurs. 2015;18(2):34–5. https://doi.org/10.1136/eb-­2015-­102054. Polit DF, Beck CT. Essentials of nursing research: appraising evidence for nursing practice. 8th ed. Philadelphia: Lippincott Williams & Wilkins; 2014. Smith J, Flowers P, Larkin M.  Interpretative phenomenological analysis: theory, method and research. London: Sage; 2013. Taylor R, Thomas-Gregory A. Case study research. Nurs Stand. 2015;29(41):36–40. Watson J. Nursing: the philosophy and science of caring. Rev. ed. Boulder: University Press of Colorado; 2008. Yin RK. Case study research: design and methods. 5th ed. Thousand Oaks: Sage Publications; 2014.

Part I The Autologous Stem Cell Transplant Journey

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Hope and Determination: A Family’s Strength Lisa Wesinger, Carissa Morton, Judi Gentes, and Jennifer Holl

Gift of Love  ~Christine Henderson  Watercolor Two compassionate nurses at the bedside, cheerleading, encouraging, or holding the hand of someone who is ready to say goodbye – giving 100% of themselves – while a new life is blossoming within.

L. Wesinger (*) Transplant and Cellular Therapy, Dartmouth Health, Lebanon, NH, USA C. Morton Dartmouth Health, Dartmouth Cancer Center, St. Johnsbury, VT, USA e-mail: [email protected] J. Gentes Hematology/Oncology, Dartmouth Health, Lebanon, NH, USA e-mail: [email protected] J. Holl Hematology/Oncology, Dartmouth Health, Lebanon, NH, USA e-mail: [email protected] © The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 J. Coffey et al. (eds.), Patients’ Lived Experiences During the Transplant and Cellular Therapy Journey, https://doi.org/10.1007/978-3-031-25602-8_3

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LONGINGS

Clare Wilmot Goreau

I want to lie in a babbling brook, in the cold, healing water, And watch a red-tailed hawk circle overhead. I want to watch a pod of dolphins in Tampa Bay with my children. I want to see the hummingbirds sipping from my bee balm. I want to float on a Lilo in a swimming pool. I want three sips of India Pale Ale, and a soft-boiled egg, And a puff pastry. I want to taste rich, three-day-old lamb stew— Fat infusion, with no wine. I want to walk onto the porch in the early hours of the day, And watch the sun rise over the hills and drink my coffee. I want to feel my lungs expand as I fill them. I want to identify wild flowers in the fields and woods And under the hawk’s nest. I want to be back on my snowshoes on two feet of snow. I want to drink my own unfiltered water. I want to sit on the porch with friends who have brought Scones and jam for tea. I want to feel useful—not just beloved. I want to deadhead my flowers and weed my garden And eat raw food with dirt on it—carrots, peas, tomatoes, radishes. I want to embrace my family completely. No masks, no consideration for their dirty clothes. I want my sister to succeed and live close to me. I do not want to walk into a store. I do not want to shop. I do not want to walk into my work And be inundated by people who look sorry for me. I do want to see my grandchildren who are not yet conceived. I do want to take my grandchildren around my garden And read them stories about how the world was made. Hope: It was the fall semester of my sophomore year in college when I started feeling like I was wasting away - I thought it was because I was tired and not eating much due to the nasty school food and then I got a cough that didn’t go away for 4 weeks - my lymph nodes were swollen - my PCP put me on antibiotics with a plan to monitor the lymph nodes over one week - but they didn’t shrink.

Growing up on the family-owned dairy farm amid the rolling Green Mountains of Central Vermont was the foundation of Hope’s strength and determination on her cancer journey. The dairy farm has been in her family for many generations. Hope was a sophomore in a four-year nursing program when she presented to her primary care provider after 4 weeks of cough, fatigue, poor appetite, and enlarged lymph

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nodes in her neck and axilla. A complete blood count (CBC) was obtained, and Hope was sent home with antibiotics. After a few days, the primary care provider called Hope and told her the results of her CBC were “off.” The white blood cell count was 28,000, hemoglobin of 11.6, and a platelet count of 573,000. The doctor referred Hope to a hematologist for further evaluation. Fear of the unknown not only paralyzed Hope but also her parents, younger brother, and extended family. After meeting with the hematologist and reviewing possible diagnoses, a lymph node biopsy of the left axilla was obtained. Hope: I had a biopsy of the lymph node under my arm the day after Thanksgiving. It took what seemed forever to get the results. The call that would forever change my life came while I was in my anatomy and physiology class.

The final pathology results confirmed a diagnosis of Hodgkin’s disease. Almost all cases of Hodgkin’s disease arise from B lymphocytes. Because lymphoid tissue is found in many parts of the body, Hodgkin’s disease can develop almost anywhere in the body. Most often, however, it arises from lymph nodes in the upper part of the body, such as the neck, chest, and axilla. The disease then spreads through the lymph vessels in a stepwise fashion, from lymph node to lymph node. Rarely, and only during the later stages, does it invade the bloodstream and spread to other parts of the body, such as the liver, lungs, and/or bone marrow. Albert: When Hope was diagnosed, pretty much the bottom dropped out of everything you know - your heart just sinks and there’s nothing you can do except trust in God and the people caring for her - trust that things will work out.

After completing a bone marrow biopsy and positron emission tomography (PET) scan for staging purposes, Hope was found to have nodular sclerosing Hodgkin’s lymphoma, stage IVA disease involving her neck, axilla, mediastinum, groin, spleen, and lungs. Hope immediately began treatment, which included the recommendation for six cycles of ABVD (Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine). After 3 cycles of ABVD, a PET scan revealed that the disease had responded, though not completely. In light of the CD20 staining that was positive, Rituximab was added for the remaining cycles. With the addition of Rituximab, Hope finally achieved a complete response on the PET scan (Table 3.1). A follow-up PET scan two months later, however, revealed recurrent disease in the mediastinum and right axilla. The primary hematologist discussed additional treatment options with Hope and her family. She agreed to undergo five cycles of ICE (Ifosfomide, Carboplatin, and Etoposide) followed by an autologous hematopoietic stem cell transplant (HSCT). Autologous HSCT remains the treatment of Table 3.1  Induction chemotherapy, ABVD A   Doxorubicin 25 mg/m2 IV on Day 1, Day 15 B   Bleomycin 10 units/m2 IV on Day 1, Day 15 V   Vinblastine 6 mg/m2 IV on Day 1, Day 15 D   Dacarbazine 375 mg/m2 on Day 1, Day 15 Repeat cycles every 28 days for up to 8 cycles

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Table 3.2  Re-induction Chemotherapy, ICE I   Ifosfomide 100 mg/m2 IV on Days 1, 2, and 3 C   Carboplatin AUC 5 IV on Day 2 E   Etoposide 5000 mg/m2 IV on Day 2    Mesna 5000 mg/m2 IV on Day 2

choice for patients like Hope with refractory Hodgkin’s disease who have failed or relapsed after induction chemotherapy. Multiple studies have demonstrated prolonged disease-free survival using this approach (Table 3.2). Hope: When we stopped chemotherapy after 6 cycles, I thought I was good to go. But a few weeks later I felt a lump in my armpit - I was trying to make excuses that it was something else such as scar tissue, but I knew that it was probably the disease. When I was told that my Hodgkins had come back, it only confirmed what I knew deep down but hadn’t wanted to admit to myself and others. There were so many emotions and thoughts swirling in my mind. When the doctor told me my PET scan was positive; I was most upset that I was not done treatment and that the new chemo/ transplant plan would mean that I couldn’t return to my junior year of college that fall (at my college that meant that I would end up a year behind, based on the way the semesters are scheduled with classes). I was upset that I wouldn’t be able to graduate with my classmates that I had become friends with and that I didn’t know anyone from the class below me. I was the first in my family to attend college, and I was very determined to be the first to become a college graduate and start the career I always wanted. I was scared of dying and never getting better—although if that was the end result, I was more worried about the feelings and grief of my family and friends. I always thought more of my loved ones than myself; their thoughts, feelings, and hardships regarding my journey through cancer. I was scared and upset that my dreams may never come true. I had always wanted to be a mother and have a family with children. Albert: Hope’s diagnosis was a never-ending thought in my mind. If I had a moment where I wasn’t concentrating on something very important during my work day, she was all I could think about. It was very hard to sleep at night because all that would go through my mind were the what ifs, the whens and it just overtook every aspect of my life - but we all had each other. Hope: I had chemotherapy every other Thursday. I would go to my nursing lab in the morning for two hours and then my parents would pick me up to go to the infusion room. I was a little more tired than normal but I could still do all the work. I had to be assigned patients who were not contagious or sick. Albert: You almost had to put on an act to be strong even when you’re not - my wife tends to keep all her emotions bottled up inside and doesn’t say anything - I had to do most of the talking - I’m the one who told our teenage son. Overall, I think we all became closer and more supportive of one another - we were all in it together. Our son would ask random questions, “Am I going to get it?” - he researched everything and he’s like his mother by keeping things to himself. At the time, he and I were motocross racing on the weekends  - we would talk in the truck going to and from the events  - we became closer during those rides. On Hope’s chemotherapy days I would get up early and milk the cows, get cleaned up and go. I had a couple of guys who helped out during the day. My wife and I would drive an

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hour and a half to pick Hope up from college, drive 30 minutes to the cancer center outpatient clinic, attend her doctor’s visit, and hang around while she received her chemotherapy, then drive 30 minutes back to her college to drop her off and then trek all the way home. I’d come back and make sure everything on the farm was done. I didn’t rest at all - that’s okay that’s my life. The ICE was harder on her - she’d come back from the outpatient chemotherapy looking like a skeleton. That was the only time I really saw her down - she said “I won’t do this again dad”, but I bet she would.

Autologous stem cell transplant uses high dose chemotherapy to treat disease, then pluripotent hematopoietic stem cells (HSCs) to rescue the bone marrow. The stem cells are highly specialized, self-renewing cells capable of maturing and differentiating into red blood cells, white blood cells, and platelets. In an autologous transplant, the patient receives their own stem cells. These stem cells may be collected directly from the bone marrow via a bone marrow harvest procedure or from the peripheral blood through apheresis. Apheresis is the removal of blood plasma from the body by the withdrawal of blood, separation into plasma and cells, collection of the stem cells, and reintroduction of the remaining cells back to the patient. The collection of cells through apheresis is less costly, easier for the patient, and generally results in a more rapid recovery of white blood cells and platelets after transplant. Consequently, peripheral blood stem cells have become the preferred source of cells for autologous stem cell transplant. As noted above, in autologous stem cell transplant, the stem cells are used as a rescue after high-dose chemotherapy. After completion of three cycles of ICE chemotherapy, Hope’s PET scan is negative for disease, and she is ready to have her stem cells mobilized and collected for transplant. Two more cycles of ICE are given to maintain remission, and twentyfour hours after the fifth cycle of ICE, Hope is started on a granulocyte colony stimulating factor (G-CSF), filgrastim, at a dose of 10 mcg/kg/day. This is known as “priming.” Under these circumstances, the goal of administering G-CSF is to stimulate the marrow, causing increased production of stem cells that are released into the peripheral blood. Also known as CD34+ cells or pluripotent hematopoietic stem cells, these immature cells are able to differentiate into each of the three distinct cell lines—white blood cells, red blood cells, and platelets (National Institutes of Health [NIH] 2011). Hope’s father administers the subcutaneous injections. During this time, her counts are checked twice a week. Twelve to fourteen days after the initiation of filgrastim priming, she returns to the clinic to have a CBC with differential and a CD34+ count. The goal for mobilization is a CD34+ count above three million cells/ kg (NIH 2011). Once her CD34+ count is high enough, Hope goes to the apheresis room, an intravascular line is placed, and she is hooked up to the apheresis machine for approximately 5 h while her stem cells are collected. Albert: Everything was explained very thoroughly, we knew what was going to happen and how it was going to happen, we were told about the side effects and what the hopeful end results were going to be. The BMT Coordinator reviewed everything about the stem cell collection and I was in charge of giving Hope her shots to get her counts ramped up. I found the whole collection process very interesting.

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Table 3.3  Autologous stem cell transplant, conditioning chemotherapy CBV Day −6 Line placed Admit IVF 200 cc/h—4 h prior to chemo Orders checked by 2 BMT RNs Pre-meds Carmustine is administered on the night shift

Day −5 Day off (recovering from effects of Carmustine)

Day −4 Day −3 Concurrent Day off hydration at 1 L an hour with Etoposide, then post Etoposide for 4 h High-dose Etoposide for 4 h Pre-meds and mid-meds to prevent hypersensitivity reactions, i.e., fever, rigors, SOB, hypotension

Day −2 EKG IVF @250 cc/h to start 1 h prior to Cytoxan Pre-meds Mesna Cytoxan at noon Highly emetogenic

Day −1 Time/ number of bags for stem cell infusion verified with cellular therapy

Day 0 Early review of the stem cell infusion checklist 4 h of IV hydration prior to stem cell infusion Premedications After Thawing, Administer frozen stem cells

Autologous HSCT, Conditioning: Cyclophosphamide, Carmustine, Etoposide (CBV), Disease: Lymphoma Filgrastim starts Day +5 Generally are discharged around Days +11–13

The apheresis machine removes Hope’s peripheral blood and spins it in a centrifuge. A specialized apheresis nurse or cellular therapy technician then sets the machine to remove the hematopoietic stem cell (HSC) layer while the remaining blood components are returned to Hope Once collected, the HSCs are checked for contaminants (to ensure a pathogen has not been accidentally introduced during collection) and viability. The cellular therapy technician then counts the cells to determine if the target amount has been collected. The goal is generally 3–6 million cells/ kg (NIH 2011). Hope is elated to have collected the required amount in a single day. Once the HSCs are collected, the cellular therapy technician transfers the cells to a storage bag containing dimethyl sulfoxide (DMSO), a chemical preservative that helps the cells stay viable during cryopreservation. Cryopreservation involves gradually freezing the cell suspension to −80  °C and then transferring it to a liquid nitrogen tank for long-term storage at temperatures < −150 °C (Shu et al. 2014). This essentially places the HSCs in a state of suspended animation until they are thawed and ready to be returned to Hope (Table 3.3).

3.1 Day −6: Admission/Carmustine (BCNU) The day of admission finally arrives. Hope arrives at the outpatient clinic early in the morning for labs, one final visit with her hematologist, and placement of a triple lumen tunneled central line. She is admitted to the Hematology/Oncology Special Care Unit (HSCU) at 3 pm.

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The nurse, specialized in transplant, introduces herself and explains the admission process to Hope and her family. The nurse performs a head-to-toe assessment, completes all required admission paperwork, and reviews hospital routines. Then, the nurse completes a first check of all Hope’s chemotherapy doses using the baseline height and weight, making sure the orders are accurate and appropriate for the patient, with a double-check completed by another nurse for safety. Hope: I was very anxious to get to the hospital and get started with the transplant process only because that would mean I was closer to being done. It had been a long road and I just wanted to be done and get my old “normal” life back. There were definitely days leading up to the transplant that I wanted to give up, but I knew I had to be strong and get through the transplant to increase my chance of survival and beating cancer.

The nurse carefully reviews the most common side effects of Carmustine (­otherwise known as BCNU), including restlessness, nausea, vomiting, facial flushing, headache, emotional lability, and a “hungover feeling.” BCNU produces these effects because it is mixed in alcohol. Hope will receive this medication at night, so she can “sleep off” the effects. Hope will be closely monitored during the infusion for safety. The nurse confirms when Hope last took acetaminophen (Tylenol), since BCNU cannot be given if the patient has taken acetaminophen or acetaminophen-containing products in the previous 72 h. This is because acetaminophen and BCNU can cause free radical damage to hepatocytes and liver necrosis when administered concurrently (Wolchok et al. 2003). Hope receives her pre-hydration and pre-medications as scheduled. The 3 hour infusion of BCNU starts in the evening, since infusing BCNU over a longer duration has been shown to lessen the severity and occurrence of adverse reactions. Unfortunately, Hope became nauseous and experienced emesis within 2 h of the start of the infusion. She is given an antiemetic, Lorazepam IV, and 30 min later when the nurse assessed Hope, the nausea has not resolved, so she receives a second dose of Lorazepam IV. By the end of the infusion, her nausea has improved and she is able to sleep the rest of the night. Hope: The chemo schedule had been explained to me and my family prior to admission, so I was semi prepared for what to expect; although I don’t believe anyone can be fully prepared. My experiences with chemo up until this point had been “easy” I would say with minimal side effects/complications. That night, when I received BCNU, it opened my eyes! I remember going into the bathroom and looking into the mirror at my face being as red as a lobster, feeling dizzy and very “off” (not my normal self). I used to say that when I received any chemo it felt like I was on drugs—not that I really know what recreational drugs are like. I just knew it was a horrible feeling to feel and the only way I know to describe it is “blah” and not my normal self. This night with the BCNU was much more intense and rough—I asked “why me” and just wanted it to be over! The nurse had a number of years experiencing this chemotherapy with other patients; she sat with me and was able to comfort and reassure me. I greatly appreciated this as my mom had to leave to go home to sleep for work since the BCNU started at 10 pm. Then it came, the nausea and vomiting, I had never gotten sick with any chemo and could probably count on one hand the times I had vomited in childhood. The nurse gave me anti-nausea medications and I was finally able to fall asleep.

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3.2 Day −4: Etoposide After a rest day, it is Day −4; Hope is scheduled to receive high-dose Etoposide. The nurse reviews the main side effects of high-dose Etoposide and the plan for symptom management. Etoposide belongs to a class of chemotherapy drugs called plant alkaloids. This particular drug, which is derived from chemical compounds called podophyllotoxins found in the May apple plant, is known to cause hypotension, fevers, chills, rash, hives, and itching. These symptoms are consistent with Type I hypersensitivity reactions and can also include bronchospasm, angioedema, and feelings of impending doom. These types of reactions generally occur during or shortly after drug administration. The nurse reassures Hope that she will be monitored frequently throughout and immediately following the infusion to assess her for these symptoms. She will receive medications to help prevent these reactions. These medications include Benadryl and an appropriate dose of IV Hydrocortisone, based on her body weight, prior to and 2 hours into the etoposide infusion. To prevent hypotension, high-dose Etoposide is administered concurrently with large volumes of IV fluids. High-dose Etoposide can also cause nausea, vomiting, diarrhea, and mucositis. The nurse instructs Hope to continue diligent mouth care and perirectal hygiene to prevent infection. The nurse reviews options for antiemetic medications should Hope experience nausea or vomiting. Hope receives her pre-medications and hydration as scheduled, and the four-­hour infusion of Etoposide is started at 1400. She becomes nauseous and vomited multiple times. The RN administers Ondansetron IV with good effect and Hope’s nausea subsides. At the end of the infusion, Hope spikes a fever (T-Max 39.2). F ­ ollowing the institutional Guidelines for Neutropenic Fever, she is pan cultured and a chest x-ray is obtained. The treatment team decides against IV antibiotics since Hope is not yet neutropenic and fever is a common side effect of Etoposide. In addition to routine supportive care, Hope is scheduled to receive high-dose Etoposide (60 mg /kg). Hope: Etoposide day they pumped the IV fluids into me as fast as the pump will go, making me need to use the bathroom more frequently. The nurses measured how much fluid goes into your body and how much goes out. I didn’t want to bother the nurses to empty the hat in the toilet so I would dump it and write down the totals. Again, this chemo made me extremely nauseous and I vomited several times. I would just vomit in the toilet so that the nurses wouldn’t have to clean that up either, which looking back is very silly to think and very gross to vomit straight into a hospital toilet. I would only call them when I couldn’t stand it anymore and they would give me something more for nausea. I am not sure if this is an attitude/quality of many young adults or just stubborn people. I ended up getting a fever—the nurse drew more blood and I had to go down to get a chest x-ray, which was the last thing I wanted to do at that moment.

3.3 Day −2: Cyclophosphamide After another rest day, it was Day −2. In addition to routine supportive care, Hope was scheduled to receive high-dose cyclophosphamide (100  mg/kg). Cyclophosphamide is an alkylating agent related to nitrogen mustard. Potential side

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effects of this drug include hemorrhagic cystitis, delayed nausea/vomiting, cardiotoxicity, mucositis, and diarrhea. In very high doses, cyclophosphamide is cardiotoxic and can cause rapid-onset congestive heart failure, which can be fatal within 10–14 days of onset. An EKG must be obtained and verified by the physician before this drug can be administered. The drug may need to be held if the EKG is abnormal. The nurse informed Hope that highly emetogenic agents, such as cyclophosphamide, may cause nausea and vomiting for up to 72  h after administration. Therefore, a longer-acting 5-HT3 antagonist, such as palonosetron, is needed. Its effects last up to 3–5 days, which makes it a good drug to prevent delayed nausea and vomiting. Cyclophosphamide can also cause hemorrhagic cystitis (bleeding in the bladder). Cyclophosphamide and other alkylating agents form a specific metabolite, acrolein, once the drug is activated and metabolized by the liver. Acrolein is toxic to the bladder. As this metabolite builds up, it binds to receptor sites in the bladder mucosa, which results in inflammation and eventual bleeding from the bladder wall. To prevent hemorrhagic cystitis, Hope is given aggressive hydration before and after the administration of cyclophosphamide. She is encouraged to empty her bladder frequently and also starts on a medication called Mesna. Mesna binds with acrolein in the kidneys, effectively inactivating the metabolite and allowing it to be eliminated in the urine without causing hemorrhagic cystitis. To monitor for this, a urinalysis is sent prior to administration of the cyclophosphamide and the next 2–3 mornings as well for continued monitoring while receiving this agent. After performing a thorough head-to-toe assessment and placing the plan for the day on her whiteboard, the nurse reviewed the main side effects of cyclophosphamide and summarizes the plan for symptom management. Hope receives the pre-medications and hydration as scheduled and the two-hour infusion of cyclophosphamide is started. She tolerates the infusion without complication; however, 2 hours after the drug is stopped, she has not voided. She receives 20 mg Furosemide IV to facilitate the complete emptying of the bladder. A repeat urinalysis is ordered. It did not show the presence of erythrocytes or other evidence of bleeding. Over the next several days, she is closely monitored for the development of hemorrhagic cystitis. Thankfully, she never develops that complication. Hope: On Cytoxan day I got a lot of IV fluid; mesna to help protect my bladder; and more medicines to help prevent nausea and vomiting. The mesna has a distinct smell and I had remembered the smell from when I got it with ifosfamide (part of ICE protocol). At my afternoon weight check, my weight was up from the morning weight and I had not voided enough, so I needed Lasix. Having Lasix for the first time was also strange and I never would have guessed that I could pee that much. And for the third time the nausea and vomiting hit me hard. That is pretty much all I remember from the week of chemo. It is a blur— getting sick more times than I can count; the “blah” feeling; and sleeping. The “off” days prior to my stem cell reinfusion day were much needed! I don’t really recall much of them as they were spent in the chemo fog with the “blah” feeling. The nurses would come in when they needed to but otherwise I just slept or stared at the TV trying to make time go by quicker. I brought several things to do to occupy the time but never felt like doing anything in particular.

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The day before stem cells are infused, the nurse checks to see exactly what time the Cytoxan finished the day before since stem cells cannot be given until at least 36  h after the completion of Cytoxan to allow adequate time for this drug to be eliminated from the body. The nurse also contacts cellular therapy to confirm the timing and number of stem cells to be infused.

3.4 Day 0: Stem Cell Infusion The big day is finally here!! Hope is scheduled to receive her HSCs. Although a total of two bags are collected from Hope during the HSC mobilization process, only one is re-infused. The other remains in long-term storage in the event Hope needs another transplant sometime in the future. Administering too many bags/syringes at once can result in adverse reactions, ranging from mild events like hypotension to more life-threatening events like cardiac arrhythmias, acute renal failure, and respiratory depression. In some cases, these adverse reactions have been directly linked to the cryopreservative, DMSO. Additional factors, such as the lysis of red blood cells followed by the subsequent release of hemoglobin, electrolytes, and membrane fragments, coupled with the infusion of high numbers of damaged granulocytes that did not survive the freezing process, can also trigger these adverse reactions. If there are a high number of bags/syringes to be re-infused, they will be divided into two separate administrations, both given on Day 0, several hours apart, with additional hydration in between. The syringe of HSCs is infused over approximately 5 min. Studies have shown that prolonged exposure to DMSO can directly impact cellular function and growth. This depends largely on the type of cell, the stage of cell development, the specific DMSO concentration, and the duration of exposure. The longer the thawed stem cells are exposed to DMSO, the greater the potential that the DMSO will inhibit cellular proliferation and influence both short- and long-term bone marrow engraftment. It is important to note, cryopreserved stem cells typically contain a 10% DMSO solution, which is hypertonic. The rapid infusion of cryopreserved cells into a normal isotonic blood system can cause extreme cell volume expansion and potential osmotic injury to cells, leading to cell death. The loss of stem cell viability can still occur, even when exposure to DMSO is minimized. Throughout this entire process, the LNA obtains vital signs before and after each syringe. The RN closely monitors Hope, asking about any side effects she is experiencing. DMSO can induce histamine release and affect the central limbic-­ hypothalamic pathways, which contributes to the bulk of its side effects. Thankfully, she only reports a minor scratch in the back of her throat, a cough, and a bad taste in her mouth, all of which quickly dissipate once the infusion stops. Hope: When it was finally my stem cell day I actually felt awake and back to reality, for a little while at least. I only had one syringe of cells. The LNA came in and set up the automatic vital sign machine and warm water bath and my room quickly became crowded as the cell therapy technician, RN, and LNA surrounded my bed (my mom and dad had to work because they had

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already used most of their vacation time bringing me to chemo leading up to my relapse). The nurse was amazing and explained everything before it happened. She made me feel comfortable. The stem cell infusion was not as exciting as I had imagined in my head. I got the tickle/ bad taste in the back of my mouth—I just kept swallowing and sucking on the lemon candies. I was so thankful that it went away quickly when the cells were all in. I wasn’t sure I could handle any more syringes—it was all I could take to get through the five minutes that felt like an eternity. I rested a while after the stem cell infusion, as Benadryl wore off. When my parents came that evening we went for a walk off the unit around the hospital. It was really the first real walk I took since being admitted. I had to wear a thick mask to protect myself from germs and it made it harder to breathe but it felt good to leave my confining room. I was very thankful that I could walk around the hospital after hours with my family because I hated the idea of walking around the circular hallway of the unit. I felt that everyone would stare at me and walking 40 times around to make a mile seemed very boring.

3.5 A Quick Review of Some Potential Complications 3.5.1 Fluid Overload Pulmonary edema is one of the earliest complications following autologous stem cell transplant. The onset is usually rapid, and it can have deadly consequences if not addressed quickly. Patients present with dyspnea, weight gain, and bibasilar crackles and reduced oxygen levels. The medical team monitors input and output and weight changes, as well as a physical exam to determine if the patient needs a diuretic.

3.5.2 Electrolyte Abnormalities Studies show that low levels of serum electrolytes are extremely common before and after autologous HSCT. This could be due to reduced oral intake and fluid loss due to vomiting and diarrhea—although there are many other factors that are not as well understood.

3.5.3 Mucositis Mucositis prevention is key in this patient population—as up to 80% of patients who receive CBV conditioning will develop some form of mucositis. Because the chemo attacks the rapidly dividing cells lining the whole GI tract, it can cause breaks in the mucosa to occur, creating a direct portal for pathogens to enter the bloodstream and exposing patients to developing life-threatening infections. To help prevent mucositis, Hope is given and instructed to use Supersaturated Calcium Phosphate (Caphosol) four times daily, after each meal and at bedtime. She is also encouraged to rinse with normal saline several times throughout the day. If a patient does develop mucositis, pain control becomes a priority. Mild forms of the condition can be managed with topical medications. More severe forms are treated systemically—commonly with patient-controlled analgesia (PCA).

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3.5.4 Anemia and Thrombocytopenia Daily CBCs are drawn and Hope is transfused as needed per protocol to keep her hemoglobin above 7g/dL and platelets above 5000 or as otherwise determined. Hope: The days after my stem cell infusion went by slowly, it seemed. I would continue to need IV electrolytes; do my caphosol rinses; try to drink at least two liters of fluid; try to eat; and walk when my family came. My appetite decreased but I would still eat some of the food my parents brought me. The cafeteria food was repulsive to me as I am a very picky eater; although I did try some items off the menu. I think I also blocked out the fact that I did get a little esophagitis. After thinking back on my transplant and reading nursing notes I do remember getting a very bad sore throat and one sore in the back of my mouth—even though I was diligent with oral care. I needed a couple transfusions. I remember one platelet transfusion clearly because I developed hives. At the time I didn’t know what hives were and just thought there must have been a bug in my hospital room—a silly thought. The night that I developed my neutropenic fever was the first time I experienced chills and rigors with a fever. The shaking rigors that you cannot stop were one of the worst feelings that I never want to experience again. Again they sent blood and urine cultures and chest x ray. I really didn’t want to go down to x-ray even more than the first time—I just wanted to sleep in my cocoon made of warm blankets.

On stem cell day, Hope is started on a triad of anti-infective medications consisting of an antiviral, an antifungal, and an antibiotic. These medications are designed to reduce the incidence and severity of opportunistic infections in stem cell transplant patients while their immune system is not fully functioning. Acyclovir helps prevent the reactivation of herpes simplex virus (HSV) and varicella zoster virus (VZV). Both HSV and VZV can cause significant morbidity in the transplant population. Fluconazole helps prevent opportunistic fungal infections such as Candida, which can cause bloodstream or deep tissue infections in stem cell transplant patients. These infections carry high mortality and can easily disseminate to other tissues such as the heart valves, eyes, liver, or spleen. Often, central lines and/or the lesions caused by mucositis serve as a direct portal of entry for microbes to enter the bloodstream. Lastly, levofloxacin is started as a prophylactic broad-spectrum antibiotic, targeting Gram-negative and Gram-positive bacteria. Eighty-five to 90% of all infections that develop in neutropenic patients are caused by bacteria which could be due to mucositis and/or severe neutropenia. Of course, if Hope developed a neutropenic fever, the protocol would be followed and she would switch to an IV antibiotic such as Cefepime until her absolute neutrophil count (ANC) recovery was above 500. Hope was encouraged to follow the neutropenic diet during her stem cell transplant hospitalization and at least 100 days immediately following. The neutropenic diet eliminates raw (uncooked) foods, raw fish, undercooked (rare) meat, deli meat and unroasted nuts plus unpasteurized foods/beverages, soft cheeses, etc., to minimize the risk of developing a severe food-borne illness, encouraging safe food practices for washing, cleaning, and storage. However, some research has recently shown that there may be little difference in infection rates between patients who follow a strict neutropenic diet versus those who do not.

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Hope is closely monitored for signs and symptoms of potential infection throughout her admission. If any infection signs or symptoms arise, quick actions will be taken to send the appropriate cultures, perform standard tests, and begin empiric antimicrobial therapy.

3.5.5 Infertility Despite her young age, Hope had always known she wanted to be a mother. She researched fertility after stem cell transplant and became concerned she would never be able to get pregnant if she is “cured.” How chemotherapy affects fertility is dependent primarily on the type of drug being used. Other factors to consider include the patient’s age, along with the type and extent of disease being treated, as well as the drug dose, dosing interval, and route of administration (oral versus intravenous). Alkylating agents in particular carry a high risk of ovarian damage. These drugs result in the loss of follicles by starting a chain reaction that leads to hypergonadotropic hypogonadism and subsequent cessation of menses. The effects on the ovary are both permanent and progressive. This is especially true with cyclophosphamide, which is used to treat breast cancer, leukemia, and lymphoma and is one of the drugs Hope received as part of her conditioning regimen in preparation for stem cell transplant. Given these concerns, her primary hematologist sent her to a reproductive endocrinologist for a consultation. Although embryo cryopreservation was once the only standard option for fertility-sparing treatments, the American Society of Reproductive Medicine now considers oocyte cryopreservation the standard procedure to preserve fertility after chemotherapy. Since the timing of ovarian stimulation and oocyte harvesting are not dependent on the menstrual cycle, as they are with embryo cryopreservation, only 2–4  weeks are required for this procedure. Additionally, improvements in technique have resulted in similar rates of live birth compared with embryo cryopreservation. Unfortunately, at the time Hope had her transplant, harvesting and freezing her eggs to preserve fertility was deemed too “experimental.” She had already begun ICE chemotherapy due to the aggressiveness of her Hodgkin’s disease and would soon receive high-dose chemotherapy for transplant. In an effort to put her ovaries into hibernation and try to preserve function, Hope was given two options: she could remain on the oral contraceptive she was currently taking or switch to the contraceptive shot, Depo Provera. Hope decided to remain on her current contraception due to the extra risks and side effects associated with Depo Provera. Hope: When I found out that the chemotherapy with my future stem cell transplant could make me infertile I was very upset. It was another dream that my cancer could possibly take away from me. I ended up seeing a reproductive endocrinologist - I was a scared 20 year old entering that exam room not knowing what to expect; not knowing if there were any possible options to save my fertility. The doctor I saw was older and did not have a very sympathetic bedside manner. I left in tears because I felt that he thought I was a silly little girl that should not be thinking about future children when I was fighting an aggressive cancer diagnosis. After this I just stayed on my birth control and hoped and prayed that one day my dreams would still be able to come true.

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3.5.6 Day +2: Start of Discharge Teaching Once Hope received her stem cells, she begins to focus on preparing to go home. Although she received a copy of the discharge instructions before she was admitted, she hadn’t really been able to concentrate on this aspect of her care until now. The nurse sets up a time to meet with Hope to begin reviewing the discharge handout she received prior to admission. She is instructed to highlight any areas she had questions about. The nurses review the discharge information with her throughout the remainder of her hospitalization until Hope feels well-prepared for her eventual discharge. Albert: There was somebody there everyday - my wife took off as much work as she could I’d arrange my schedule so I could get there.

3.5.7 Day +5: Initiation of Granulocyte Colony Stimulating Factor (Neupogen) Five days after receiving her stem cells, Hope resumes the granulocyte colony stimulating factor (G-CSF) filgrastim (Neupogen). Although this drug was previously used to mobilize her stem cells for collection, following stem cell transplant, filgrastim and other G-CSFs are also used to limit the severity and duration of neutropenia. Studies show that the use of G-CSFs after autologous stem cell transplant accelerates the recovery of neutrophils, reduces the rate of infection, and decreases the length of stay, resulting in improved patient outcomes and decreased costs. Hope receives G-CSF until her absolute neutrophil count (ANC) was greater than 1500 cells/mm3 on two consecutive days or greater than 5000 cells/mm3 once post-­ engraftment. The addition of G-CSF means she may expect neutrophil engraftment to occur approximately 10–14 days after receiving her stem cells.

3.5.8 Day +11: Discharge Home Hope’s treatment team determines that she is finally ready for discharge. Her ANC is greater than 500; she has been without a fever and off antibiotics for more than 24 hours without evidence of active infection. She is eating well, was able to tolerate oral medications, and is drinking 2–3 liters of fluid per day. Most importantly, she understands the need for ongoing medical management post-transplant and has ­reliable, well-informed caregivers who are present and available to care for her after she goes home. Following a unit of platelets, she is taken to the department of Interventional Radiology to remove her central venous access device (CVAD). Once back at the bedside, her nurse monitors her CVAD dressing to make sure there is no evidence of bleeding or hematoma formation. The discharge plan was once again reviewed with Hope and her family. After all their questions have been answered and everyone felt comfortable with the plan of care, Hope leaves the hospital and heads home.

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Hope: A couple days before discharge my nurse sat down to review the transplant discharge packet with me. I had already read this several times prior to admission. I also had been asking questions periodically throughout my admission. On discharge day it was chaotic. I needed platelets, to get my central line removed, and to wait for the team to get the paperwork done. It is difficult waiting around when you just want to be home in your bed that you missed for the last few weeks. Even though I didn’t get to leave until late afternoon I was still thankful to be home. Albert: I felt a little apprehensive when it was time for Hope to come home. When Hope came home she had to live in the house she and her husband are living in now because at our home we burn wood and this house has an oil furnace. Hope just gets what has to be done - there was no transition to home - she was happy to be home. We were here during the day but she insisted we go home at night - she didn’t have that 24 hour supervision - one night she called us because she was having a hard time breathing. Her mother took her back to the hospital where she was admitted for a few days - that was rough - you just don’t know what’s going on and I couldn’t be with them - I couldn’t leave the farm - that was probably one of the hardest days for me - but they changed a few things and she got better.

3.5.9 Post-Transplant Care Full immune reconstitution generally does not occur until six months post-­ autologous transplant, leaving the post-transplant patient at risk for infection. Other complications of stem cell transplant include relapsed disease, regimen-related toxicity, psychological complications, bone disease, fertility issues, and the development of secondary malignancies. Studies indicate early identification and intervention in these and other chronic health problems experienced by stem cell transplant recipients result in less need for systemic therapy, improved outcomes, and higher quality of survivorship. Consequently, stem cell transplant recipients need an evidence-based plan of care that encompasses appropriate and timely screening, as well as preventative services, to optimize their outcomes. Post-transplant recipients are generally seen in the outpatient hematology clinic within 2–5 days of discharge, then weekly, thereafter as needed. The first formal re-evaluation occurs on Days +30, +100,+180, and + 365, then annually thereafter or as otherwise indicated. Blood work including CBC, liver and kidney function, electrolytes, and some lymphoma markers are drawn, followed by a provider visit with complete history and physical examination. This is done to ensure adequate surveillance for engraftment, infection, treatment-related toxicities, disease status, and overall clinical condition. The CDC has approved flu shots at 6 months after transplant and the remaining vaccines between 1 year and 2 years post-transplant with MMR being the last one given at 2 years. The CDC also describes that transplant recipients may have some immunity left, their titers may still be adequate, but it may decrease over the years after myeloablative chemotherapy. Albert: I’m optimistic, my wife is pessimistic so together we are perfect. I’m a dreamer and I work hard. I always try to be kind to everybody I meet and try to stay upbeat whether I am or not because the kinder you are to someone else the kinder they’re going to be to the next person - put that forward in the world and it makes for a better place to live. I don’t think this experience has changed how I look at myself - in fact, I may want to be an even better

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L. Wesinger et al. person. When I leave this world I want my family to inherit the farm and be able to make a living here and live a good comfortable life. Hope: The follow up appointments were frequent after leaving. I didn’t mind since I was used to going to the clinic pretty frequently prior to my transplant. The hospital becomes like a home to cancer patients- even though they would all prefer to not be there. The secretaries and nurses learn your name and situation and genuinely care. Once my appointments were less frequent it felt very strange to not be at the clinic so often. I got back to my “normal life” going back to school and time began to pass quickly. I kept track of the number of days since my transplant and soon it was day 100 (the first PET scan after transplant). When I would get my appointment reminder letter in the mail for this check, and all of my check-ups after that, I would get very nervous, terrified that the PET scan would be dirty and my Hodgkin would be back with a vengeance. I don’t know if the fear in the back of my mind will ever go completely away, but the further out I am it seems to get a little less. One thing that I reflect upon often is that every person diagnosed with cancer has a different journey and no one person can know how a person is feeling or what they are going through. I think Siddhartha Mukherjee, MD, PhD (author of The Emperor of All Maladies) says it best in The 2nd Episode of Ken Burns Documentary: ‘Emperor of All Maladies’-“There’s no archetypal response to cancer. Patients have different responses. This woman’s or this man’s struggle – this child’s struggle – is his or her own. As family members, as loved ones, as physicians, we might be able to witness it but it’s not ours.” It is now creeping up on 6 years since my autologous stem cell transplant. In some ways it seems like yesterday and in others it seems like a whole lifetime ago. I finished my five years of follow up checkups and I am no longer officially followed by my hematologist. This is both exciting and scary at the same time. After my transplant I finally ended a relationship that was not good for me—it was difficult to do this while being sick because it was nice to have someone always there for me. I have now seen other cancer patients in this same position and I applaud the ones who are or were strong enough to end unhealthy relationships in the midst of a serious illness. I returned to college about a month and a half after I was discharged and graduated one year behind my original class with a Bachelors in the Science of Nursing. I passed my NCLEX- RN exam and started the job that I never imagined I would have wanted or love; as a RN working aside the nurses that cared for me in the Hematology/Oncology Special Care Unit—taking care of stem cell transplant patients as well as other hematology patients. I eventually found my perfect match, who is now my husband. It is difficult as a young person who has had cancer to enter a serious relationship. You have to tell your partner your situation and worry about their reaction and if they will accept you. When I told my husband my whole story, after a couple dates, I was relieved by his acceptance and support. He reminded me that yes my Hodgkin’s could come back but anyone could be hurt or die in an accident at any time as well. We eventually discussed our desire to have children one day, and then had to discuss the fact that I may not be able to have my own biological children. He was more than supportive and was open to other options when that time came in our life. After we got engaged my hematologist referred us to a reproductive endocrinologist (a different one from prior to my transplant). The doctor we saw this time was wonderful; she validated my feelings and did not make me feel silly in any way. She ran all of the appropriate tests and I found out that I still had some eggs although not as many as an average person my age (sometimes the chemo can deplete the remaining eggs a woman is born with) and that my body was still making adequate levels of hormones necessary to become pregnant. She encouraged us that if we had trouble getting pregnant that they would investigate the situation more, sooner than they would for other couples with a benign medical history—I was very thankful after this appointment and my fears were somewhat calmed. My husband and I were married and started trying to have a family- as we thought it would take a while given the history. We were shocked when we found out we were pregnant with a honeymoon baby. My pregnancy was deemed a low risk by a high risk obstetrician and I was able

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to have my pregnancy monitored by the midwife team. In March 2016 I gave birth to my happy, healthy miracle three and a half weeks early. I am beyond grateful to have been blessed with the baby I always had dreamt of. Although I still worry about the “what ifs”: “What if I get sick again? What if I die and she grows up without a mom? What if she develops some disease or illness because of my history?” I realize all we can do is hope and pray that my family and I stay happy and healthy—so that is what we do. I am blessed to be in the position I am today and have had most of the dreams, prior to my Hodgkin’s, come true. I work alongside some of the most passionate, compassionate, and caring nurses I have ever met. I am able to care for the patients I am most passionate about and am able to try to make each of their journeys a little easier with my unique sympathetic perspective. I am thankful to maintain a relationship with my hematologist, who is now a colleague. Looking back she is the only doctor I could have imagined having during my journey; smart, strong, and honest; and I am eternally appreciative for all that she has done for my family and me. I look forward to what the future has in store for my little family.

References Shu Z, Heimfeld S, Gao D.  Hematopoietic stem cell transplantation with cryopreserved grafts: adverse reactions after transplantation and cryoprotectant removal prior to infusion. Bone Marrow Transplant. 2014;49(4):469–76. https://doi.org/10.1038/bmt.2013.152. U.S. Department of Health and Human Services, National Institutes of Health. (2011). Chapter 5: Hematopoietic stem cells. In Stem cell information. Retrieved from http://stemcells.nih.gov/ info/scireport/pages/chapter5.aspx Wolchok JD, Williams L, Pinto JT, Fleisher M, Krown SE, Hwu WJ, et al. Phase I trial of high dose paracetamol and carmustine in patients with metastatic melanoma. Melanoma Res. 2003;13:189–96. https://doi.org/10.1097/01.cmr.0000056216.78713.77.

Suggested Readings American Cancer Society. (2016). Hodgkin disease. Retrieved from www.cancer.org/cancer/ hodgkindisease/detailedguide/hodgkin-­disease-­what-­is-­hodgkin-­disease Bailey AP, Ginsburg ES. Fertility preservation options for females. In: Quinn GP, Vadaparampil ST, editors. Reproductive health and cancer in adolescents and young adults. New York, NY; Dordrecht; Heidelberg: Springer; 2012. p. 9–28. Burkhart MC, Wade J, Lesperance V. Evidence-based guideline recommendations: post-hematopoietic stem cell transplantation. Clin J Oncol Nurs. 2013;17(5):63–7. Gobel BH.  Chemotherappy-induced hypersensitivity reactions. Oncol Nurs Forum. 2005;32(5):1027–35. Groopman JE, Itri LM. Chemotherapy-induced anemia in adults: incidence and treatment. J Natl Cancer Inst. 1999;91(19):1616–34. Horning SJ, Chao NJ, Negrin RS, Hoppe RT, Long GD, Hu W, W.,…Blume, K.  G. High-dose therapy and autologous hematopoietic progenitor cell transplantation for recurrent or refractory Hodgkin’s disease: analysis of the Stanford University results and prognostic indices. Blood. 1997;89(3):801–13. Humphreys CT, Tallman B, Altmaier EM, Barnette V. Sexual functioning in patients undergoing bone marrow transplantation: a longitudinal study. Bone Marrow Transplant. 2007;39:491–6. Janson B, Koeverden PV, Yip SW, Thakerar A, Mellor JD.  Carmustine infusion reactions are more common with rapid administration. Support Care Cancer. 2011;20:2531–5. https://doi. org/10.1007/s00520-­011-­1377-­4.

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Li Z, Mewawalla P, Stratton P, Yong A, Shaw B, Hashmi S, et al. Sexual health in hematopoietic stem cell transplant recipients. Cancer. 2015;121:4124–31. Philibert D, Desmeules S, Filion A, Poirier M, Agharazii M. Incidence and severity of early electrolyte abnormalities following autologous hematopoietic stem cell transplantation. Nephrol Dial Transplantation. 2008;23:359–63. https://doi.org/10.1093/ndt/gfm571. Romeo C, Li Q, Copeland L.  Severe pegfilgrastim-induced bone pain completely alleviated with loratadine: a case report. J Oncol Pharm Pract. 2015;21(4):301–4. https://doi. org/10.1177/1078155214527858. Sonbol MB, Firwana B, Diab M, Zarzour A, Witzig TE. The effect of a neutropenic diet on infection and mortality rates in cancer patients: a meta-analysis. Nutr Cancer. 2015;67(8):1230–8. https://doi.org/10.1080/01635581.2015.1082109. Soubani AO, Miller KB, Hassoun PM. Pulmonary complications of bone marrow transplantation. Chest. 1996;109(4):1066–77. Stiff PJ, Dahlberg S, Forman SJ, McCall AR, Horning SJ, Nademanee AP, et al. Autologous bone marrow transplantation for patients with relapsed or refractory diffuse aggressive non-Hodgkin’s lymphoma: value of augmented preparative regimens—a Southwest Oncology Group trial. J Clin Oncol. 1998;16(1):48–55. Stiff PJ, Fox-Geiman MP, Kiley K, Rychlik K, Parthasarathy M, Fletcher-Gonzalez D, et  al. Prevention of nausea and vomiting associated with stem cell transplant: results of a prospective, randomized trial of aprepitant used with highly emetogenic preparative regimens. Biol Blood Marrow Transplant. 2013;19(1):49–55. Tewari P, Franklin AR, Tarek N, Askins MA, Mofield S, Kebriaei P.  Hematopoietic stem cell transplantation in adolescents and young adults. Acta Haematol. 2014;132:313–25. https://doi. org/10.1159/000360211. Tomblyn M, Chiller T, Einsele H, Gress R, Sepkowitz K, Storek J, et al. Guidelines for preventing infectious complications among hematopoietic cell transplant recipients: a global perspective. Bone Marrow Transplant. 2009;44(8):453–5. Vadhan-Raj S. Management of chemotherapy-induced thrombocytopenia: current status of thrombopoietic agents. Semin Hematol. 2009;46(1):26–32. West F, Mitchell SA.  Evidence-based guidelines for the management of neutropenia following outpatient hematopoietic stem cell transplantation. Clin J Oncol Nurs. 2004;8(6):602–13. Wilson WH, Grossbard ML, Pittaluga S, Cole D, Pearson D, Drbohlav N, et  al. Dose-adjusted EPOCH chemotherapy for untreated large B-cell lymphomas: a pharmacodynamic approach with high efficacy. Blood. 2002;99(8):2685–93.

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The Hugger Lisa Wesinger

Out living it, 20”x 32", Gouache, milk paint and pastel, 2016 By Corbett B. Leith Painting is an adrenaline rush similar to skiing down mountains, kayaking rivers, and surfing oceans. Kayaking off a waterfall or putting a brush to canvas creates butterflies of excitement. OUT LIVING IT captures a moment in the outdoors, never to be repeated, en plein air, in the garden of The Fells, Lake Sunapee, NH. One of the days you dream about with blue sky, sunshine, floral, greenery, and the overall beauty is exhilarating and dynamic. Applying bold marks of color expressively and with confidence, the paint moves while allowing each layer to reveal the painting’s history. The layers of paint are aggressive yet sensitive the same way a river is intensely powerful or deeply serene. The artwork is completed between treatments, forged from how incredibly fun life is! Yes, out living it!

L. Wesinger (*) Transplant and Cellular Therapy, Dartmouth Health, Lebanon, NH, USA © The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 J. Coffey et al. (eds.), Patients’ Lived Experiences During the Transplant and Cellular Therapy Journey, https://doi.org/10.1007/978-3-031-25602-8_4

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L. Wesinger The Sash Lock Win Hathaway

There is no life outside of me if this is what I see, I get to choose the smoke and mirrors, the darkened room, the self-imposed screen of mortality. There is no death in the face of truth. There is no reason that one vessel should fail, and another would not. There is no purpose in the question Why when it is used to justify. No power in Wish. There is no fulfillment in Want. No honor in Passion that is self-serving. The miracle is lost when blindly sought, or when obedience is forgotten and I hopelessly hope. I remember these things, and I remember: the lock works from the inside, throw open the sash and Live. Carson: It’s difficult to say where my cancer story begins. The most logical place to start is Monday, January 13th 2014 at 10:59 AM when I checked myself into the Emergency Department. On that day, questions about my health that had lingered since at least 2012 were finally answered – a computerized tomography (CT) scan revealed an “unexpected finding,” specifically “multiple large lymph nodes, suspicious for lymphoma.” In doctor speak, the scan found “massive mesenteric and retroperitoneal lymphadenopathy anterior, posteriorly and laterally displacing hollow viscus and solid organ.” According to my oncologist, multiple tumors, too many to count and totaling over twenty centimeters of tumor mass, took up my entire abdominal cavity and surrounded crucial organs and blood vessels “in a very dramatic way.”

Carson, a 46-year-old man, presented with multiple unilateral (left-sided), nondescript musculoskeletal and abdominal complaints and a feeling of tightness and progressive insomnia, but no frank B symptoms (fevers, night sweats, or weight loss). The initial work-up was conducted for a possible ventral hernia, but an abdominal and pelvic CT scan performed in January 2014 as part of his work-up showed extensive intra-abdominal lymph node masses indicating lymphoma. Pathology was notable for an abnormal lymphoid population, while the bone was unremarkable.

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Between 1990 and 1995, Carson was in the U.S.  Army Air Defense Artillery Division. During that time, he completed a six-month tour in Southwest Asia (Saudi Arabia and Kuwait), where his unit trained the Kuwait Army on the PATRIOT missile system. It was during the Kuwaiti training exercise that he was exposed to environmental hazards, including lingering particulate matter from the oil fires in Kuwait, pesticides, and depleted uranium shells fired from U.S. Army tanks. Carson: It was on that day in January 2014 that I learned that the pain and discomfort I had experienced more acutely since the previous October was not solely caused by a ventral hernia diagnosed the week before going to the emergency room, but instead resulted from “a large tumor burden” in my abdomen that had likely been building up for quite some time. One of the tumors was large enough to have pushed through the wall of the abdominal cavity causing the ventral hernia. A positron emission tomography (PET) scan would later find two additional cancerous lymph nodes in my neck and mandible. In the nearly two years preceding my diagnosis, I had made more than a dozen visits to my primary physician and specialists complaining about ever-worsening symptoms. January 13, 2014 is the day I got the answer no one ever wants – cancer. Thoughts of cancer scared me long before I had it, and I generally avoided any discussion of it or even listening to news programs or reading articles about cancer. If I happened upon news about cancer while browsing the web, I would immediately close the browser window. If NPR aired anything even mentioning the word, I turned off the radio. As time went on, my worries about my health consumed my every waking moment and often while I slept.

Diagnosed with diffuse large B cell lymphoma (DLBCL), Carson underwent 6 cycles of R-CHOP chemotherapy with a restaging PET/CT scan showing a partial response (Table 4.1). Carson: After doctors confirmed the diagnosis, I knew I was in for a big change in life. I remembered the day when I was eleven years old and told myself that I would never need anyone for anything, but this time I knew I wasn’t going to get through cancer on my own. I knew my best chance at surviving meant that I had to somehow open myself up. Bill, one of the Licensed Nursing Assistants (LNA), always greeted me with a hug when I came to the hospital for infusion. “WonderBill” showed me the way to what I knew I needed to get through my cancer experience, even if I didn’t survive.

Ideally, before any cancer treatments begin, discussions about preserving fertility take place, but often the pace of disease is too aggressive. When feasible, this may be done urgently without multiple collections. Carson: My girlfriend at the time thought it would be a good idea and I said oh you’re right … it all happened literally within an hour … unplanned, unscripted, no pre-­ meditation … let’s go ahead and get this done because I was going to be admitted that day

Table 4.1  Induction chemotherapy, R-CHOP R   Rituxan 375 mg/m2 IV on Day 1 C   Cyclophosphamide 750 mg/m2 IV on Day 1 H   Doxorubicin 50 mg/m2 IV on Day 1 O   Vincristine 1.4 mg/m2 IV (max 2 mg) on Day 1 P   Prednisolone 100 mg by mouth daily on Days 1 to 5 Repeat cycles every 21 days for up to 8 cycles

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Table 4.2  Re-induction chemotherapy, R-DHAP R   Rituxan 375 mg/m2 IV on Day 3 D   Dexamethasone 40 mg IV daily on Days 1 through 3 H   Dexamethasone 40 mg IV by mouth once on Day 4 A   Cytarabine 2000 mg/m2 IV every 12 hours starting on Day 2 for 2 doses P   Cisplatin 100 mg/m2 IV on Day 1 Repeat cycles every 21 days to start R-CHOP … In terms of being better planned, I can absolutely see a step where you’re going to be an inpatient in a week and you’re asked “have you thought about this and if you want to do something about it now would be the time.”

Based on the finding of persistent disease after 6 cycles of R-CHOP, Carson then underwent 3 cycles of R-DHAP chemotherapy with improvement, followed by stem cell collection and autologous stem cell transplant (Table 4.2). According to Witzig et al. (2008), Grade 3 toxicities to R-DHAP include thrombocytopenia, neutropenia, fatigue, infection, nausea/vomiting/diarrhea/anorexia, and electrolyte imbalances. Carson: The lymphoma diagnosis consumes your life. For me it was a combination of pretending it wasn't happening … going through your day knowing it's there but also pushing it away … but it still ruled my life because everything revolved around the three-week cycle – how I felt, what I did, and how much I could do every day. That winter we had a lot of snow – I have a 10 foot by 6 foot heavy barn door that I can barely lift one end of alone when I’m feeling good … it had come off the rails in the middle of the snow storm … I had just finished a round of chemo and came home in the middle of a snowstorm … I thought I’ve got to get this thing back on – so I'm out in the middle of a snowstorm with a ladder trying to figure out, like an engineer, how to get this door back on its rail. Having just finished chemo, puking and everything else and I'm out there propping the thing up using every ounce of strength I had to get the door back on the rail … Call it a guy thing … nothing is going to stop me … I got it done but you know part of that was just to prove that I can go on … it's not going to get in my way. I remember talking to one of my brothers when I started R-DHAP … I told him this might not work … he said well you can't get existential about this … everybody dies, so just accept that you might not survive this. I felt like that was pretty cold, but after a while I thought he's not wrong, I had to really think about what does that mean and what if this is the end. On the upside, putting things in perspective changes your view of life and my stress level went way down because I didn't really worry about it anymore; it was sort of if it works great if it doesn't I'm fine with it. By the time I got to transplant I was in a good mental state. I was trying to live a normal life. I actually ran for legislature leading up to transplant. It was a fairly decent run all things considered … it was a good distraction, a good way to do something productive, since I wasn't really working that much … you have to figure out how you're going to cope with it.

In November 2014, Carson was admitted (on Day −6) for an autologous peripheral blood stem cell transplant. His high-dose chemotherapy conditioning regimen included Carmustine, Etoposide, and Cyclophosphamide (CBV) (Table 4.3). On the day of admission, a triple lumen central venous access device (CVAD) was inserted for his high-dose chemotherapy and stem cell infusion. At the end of the carmustine infusion, Carson experienced nausea and vomiting and was given prochlorazepine and lorazepam with good effect. He also experienced transient hypertension and

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4  The Hugger Table 4.3  Autologous stem cell transplant conditioned with CBV Day −6 Line placed Admit IVF 200 cc/ hr – 4 hrs prior to chemo Orders checked by 2 BMT RNs Pre-meds Carmustine is administered on the night shift at approximately 2200

Day −5 Day off (recovering from effects of carmustine)

Day −4 Concurrent hydration at 1L an hour with etoposide, then post etoposide for 4 hours High-dose etoposide at 1400 for 4 hours Pre-meds and mid-meds to prevent hypersensitivity reactions, i.e., fever, rigors, SOB, hypotension

Day −3 Day off

Day −2 EKG IVF @250cc/hr to start 1 hr prior to cytoxan Pre-meds Mesna Cytoxan at 1200 Highly emetogenic

Day −1 Time/ number of bags for stem cell infusion verified with cellular therapy

Day 0 Early review of the stem cell infusion checklist 4 hours of IV hydration prior to stem cell infusion Pre-­ medications Administer frozen stem cells

Autologous HSCT, Conditioning: Cyclophosphamide, Carmustine, Etoposide (CBV), Disease: Lymphoma Filgrastim (growth factor) starts Day +5 Generally are discharged around Day +11–13

complained of a severe headache which was relieved with meperidine IV x1. His symptoms improved and were fully resolved by 9 am the following day. Carson: I feel the side effects of the chemotherapy were all very well managed. In fact, one of the things I tell people about transplant is … I knew what was going to happen … the side effects were almost exactly like the nurse described – they were bad!

The main potential side effects of CBV include nausea, vomiting, headache, restlessness, fever, rigors, oral mucositis, kidney and liver effects, and cardio-toxicities. Each patient manages the experience of side effects differently. While communication is important to all patients, Carson had a definite expectation of the communication plan. Whiteboards are used in each patient room as a means of communication between the providers and patients and their family. The bedside nurse outlines the plan of care for the day, including chemotherapy, care team members, goals, fall risk, mobility needs, anticipated discharge, family contact information, questions for the team, etc. The bedside nurse reviews the chemotherapy plan for each day, potential side effects, and symptom management. Appropriately, Carson insisted on having his whiteboard up to date. Carson: I took pictures of the whiteboard everyday … I wanted to make sure all the information was up there … making sure people were coordinated because that’s one of the most frustrating things … it’s one of my biggest complaints about the healthcare system … you could talk to one person in one department and another person in another department and they don’t have the same information ... it’s really frustrating.

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L. Wesinger It only took me a couple days to get used to the unit, the staff and new surroundings. I had a lot of family and friends visit, initially, so that was nice. It couldn't have been more than a couple of days into the hospitalization when I noticed there was an extra chair in my room. So, I had all the stuff that I didn’t need taken out, and the staff brought in an extra over bed table I used as a desk, and they even found me an office chair. For me it was just like going to work … I treated everyday like I was just getting up and going to work. I would make coffee, sit down, open my computer and I'd send emails, read, or write …. I wrote two articles that were published while I was in the hospital …. I wrote an article on health care. I was very diligent about making sure I walked every day between 2 and 4 o’clock. I used an app called “MapMyWalk” to map out how far I needed to go … i.e., I needed to walk this level 3 times and then this level 4 times to get the mileage I wanted and then I would put a mask on and head out.

On Day −4, Carson received his pre-medications and hydration as scheduled and the 4-hour infusion of etoposide was started. He became nauseous and vomited multiple times and was given an antiemetic. At the end of the infusion, Carson spiked a fever (TMax 39.6) with rigors, both relieved with acetaminophen. Fortunately, the next day is a day of rest – allowing time for Carson to recover from the side effects of etoposide. Carson: I remember for several hours rolling side to side not being able to stop … like body tremors lasting for several hours it was incredibly uncomfortable … again I knew it was going to happen … I knew it was going to end … it was exactly what was described.

On Day -2, Carson received his pre-medications and hydration as scheduled, and the two-hour infusion of cyclophosphamide started at 1400. He experienced “dry heaves” relieved with prochlorazepine x1, and later in the evening he reported feeling “drowsy” and “hazy.” His Hgb dropped to 6.7 the following morning, requiring one unit of Packed Red Blood Cells. Again, the next day is a day of rest. On Day 0 (stem cell day!), Carson reported ongoing headache, neck pain, tenderness, and discomfort at the tunneled CVAD site. He also had a rash under and surrounding the CVAD dressing, felt most likely related to the tegaderm dressing. An APRN from Interventional Radiology assessed the site. A decision was made to remove the tunneled catheter after his stem cell infusion and access his double lumen mediport for the remainder of his hospitalization. Carson: The tunneled catheter was so uncomfortable … Usually they don't take it out until after transplant but I was like it's got to come out now … it caused me so much discomfort.

Carson received two syringes of autologous peripheral stem cells at the bedside without difficulty. He tolerated the procedure well. The CVAD was removed as planned and his mediport was accessed. Carson: I felt so much better as soon as they pulled the line out and got the rash under control, but between that rash and the infection it was not fun.

Throughout the remainder of his hospitalization, Carson had no fevers while neutropenic. He received filgrastim (Neupogen) daily beginning on Day +5 and by Day +10 his ANC was greater than 500. At discharge on Day +12, his ANC was greater

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than 9000. For antimicrobial prophylaxis, he received acyclovir, fluconazole, and levofloxacin per protocol. He was discharged on acyclovir for antiviral prophylaxis, but no fluconazole or levofloxacin because his counts had adequately recovered. During his admission, Carson developed a rash as a reaction to the adhesive in the Tegaderm dressing placed on his neck for his central venous catheter. After the rash appeared, Tegaderm was immediately removed, and this improved with the application of topical triamcinolone. The rash was monitored closely for ongoing resolution throughout the remainder of his admission. Upon discharge, Carson was hemodynamically stable, fully ambulatory without requiring supplemental oxygen, afebrile, and pain free. Communication frustration was another factor for Carson at discharge. It was Thanksgiving and he really wanted to go home. Carson: One doctor would come in and say “we’re going to discharge you” … then another said “oh no, we’re not going to do it” … so it was never clear when I was actually going to get discharged ... and I said “this is BS; you guys need to get on the same sheet of music, Just tell me if it’s before or after Thanksgiving … just give me a date I can count on. I don’t want to get my expectations set that I’m going home for Thanksgiving and then not be home” … in the eyes of the patient it’s a big deal.

Three days after discharge, Carson had an urgent visit to his primary hematologist for increasing pain and edema at the old CVAD site. He was diagnosed with early cellulitis and prescribed a course of antibiotics. Cellulitis was resolved by the following visit one week later. Throughout the transplant process Carson had some fears: I had a lingering question whether or not the transplant was going to work or not ... but I think I had already come to terms with whether if it didn’t work I was okay with that … I guess what I worried about was things going wrong like the infections, will I have restrictions. I had a feeling I was going to succeed at that point. I wasn’t really too stressed out about it ... I was pretty relaxed.

Prior to transplant Carson had mesenteric adenopathy in two areas and was to receive radiation a few months after his transplant: Carson: I felt it was like a good insurance policy to take out.

When asked to compare his pre-transplant chemotherapy to high-dose chemotherapy at transplant, Carson replied: Oh night and day … R-CHOP’s not bad … R-CHOP is easy in comparison … it’s a whole different ball game. There’s a woman I know who recently finished R-CHOP … she finished her 4th cycle and had some residual disease … it looked like she was going to have to go through transplant … I told her just ask questions, be as well armed as possible for what to expect … it’s as scary as people describe … you can choose to look at it as just a procedure you’re going through or look at is as sort of a holistic experience … I think my concept of transplant changed dramatically when I began to view it as not just a procedure but as a holistic experience that I’m going through … that’s very different. Who am I going to be … the person who curls up in a ball and quits or the person who gets through this … everybody has to come up with their own way of getting through …

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L. Wesinger even if somebody curls up in a ball and quits there is no judgment about that … it’s just part of the human experience.

Bone marrow transplant changed Carson in many ways: What lesson am I going to extract out of this … I’m now healthy, but what does this mean for me now … How is this going to impact how I see the world … and like any life lesson you never just learn it you have to keep learning it … keep reminding yourself not to get too far away from … I’m convinced the reason I got sick had as much to do with what was going on inside my head as it was my body. I think some people look at cancer as just something that’s happening to their body and that there’s no relationship to what’s going on mentally … it had as much to do with what was going on in my head as it did my body.

Prior to going through transplant, in Carson’s personal and professional environment hugging was not an acceptable behavior. He grew up in a family where people didn’t hug each other, it was always handshakes and that is how he lived his life – no hugging. After transplant that changed: Carson: I’m a hugger now. If I can get away with it, even professionally, I tell people you had better watch out or you’re going to get hugged, people need it, you know. Since cancer treatment, I’ve found that most people like hugs.

Reference Witzig TE, Geyer SM, Kurtin PJ, Colgan JP, Inwards DJ, Micallef IN, LaPlant BR, Michalak JC, Salim M, Dalton RJ, Moore DF Jr, Reeder CB, North Central Cancer Treatment Group. Salvage chemotherapy with rituximab DHAP for relapsed non-Hodgkin lymphoma: a phase II trial in the North Central Cancer Treatment Group. Leuk Lymphoma. 2008;49(6):1074–80. https://doi.org/10.1080/10428190801993470.

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Spaces In-Between Judi Gentes

Planting Hope  —Jeff Ryan Pencil The piece was as much about the nurses (and doctors) administering the treatments in the transplant wing as it was for me receiving the treatment. That’s why there is a nurse administering the stem cells as well as a nurse’s hand holding the patient’s hand that turns into a bouquet of flowers on the living side of the drawing. Doing the work and reassuring the patient going from the white antiseptic hospital on the left to the thriving growth of life on the right. Professional competent nurse on the left and all the while the hopeful reassurance of a nurse on the right. I can’t say enough about the staff up there in general and the transplant wing in particular.

J. Gentes (*) Oncology/Hematology, Dartmouth Health, Lebanon, NH, USA e-mail: [email protected] © The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 J. Coffey et al. (eds.), Patients’ Lived Experiences During the Transplant and Cellular Therapy Journey, https://doi.org/10.1007/978-3-031-25602-8_5

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HARVEST Blair Brooks

We harvested over the weekend. Artichokes and grapes. Too many beans to eat. Chard still going strong. The kitchen reeked of basil’s best. Ripe apples soon. The pumpkins turning orange. A colorful collage of carnival squashes. The dry summer hadn’t affected our harvest much. Fences had kept intruders out. Yesterday I was harvested. Right in season. Chemo had weeded out my bone marrow cancer cells. I was fertilized with Neupogen. Fences were only partially effective for my anxiety and bone pain. As it turned out – I had a bumper crop of stem cells. The nurses told me how beautiful my bag of collected cells looked. I came through my harvest far better than I had feared. So last evening Nancy and I went for a sunset hike. We picked beans and tomatoes for dinner And chatted about changes in planting for next spring. “Spaces In-Between” A sculptor once told me that he sought to capture “in-between” spaces, not the branches or the trunks, not the solids or the dark shapes. Rather the light defines where meaning lurks, where connections are born, where love’s origins derive. Maybe that is where joy hides, where mystery abounds and curiosity swells. The pauses. The in-betweens. Empty nothings. I paid little attention to them, until now, and had even less appreciation for them– except as a time to recover. Now, these spaces have deep, bright energy. I want to explore their richness, make up for lost time. -Blair Brooks

Bryan was the one thousandth patient to receive a stem cell transplant at the Cancer Center. He smiled as he stated that he found irony in the celebration because

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he had been a general internal physician at the same medical center for 27 years and had not received as much credit for being a physician as he did for being the one thousandth stem cell transplant patient. Bryan and his wife Natalie were both physicians; they worked at the same medical center, and between them they had approximately 57  years of service. Bryan had 27  years at retirement, and Natalie had 30 years of service at retirement. Natalie’s retirement was planned; Bryans’ was not. They had two daughters, Alexandra and Lydia. Bryan and his wife are very family oriented. They took several family trips together throughout the years. Bryan’s story started when he and his daughter went on a skiing trip in February. They had an amazing time, and he was feeling well. When they returned from their trip, Bryan was scheduled for shoulder reconstruction surgery a few weeks later. The first month after surgery, he was recovering well. The second month Bryan went back to work and started coaching crew and was giving presentations at the medical center. Bryan stated, “I was really dragging.” He thought he had done too much too soon. Natalie: Things had gotten to the point where he could not walk up a hill without getting really short of breath, normally Bryan can run 10 to 12 miles.

Bryan went to have lab work, and the lab results showed a hemoglobin level of 6.5, and a calcium level of 13. After receiving a phone call from the physician with the results, he presented to the emergency room with approximately four weeks of fatigue, body aches, exercise intolerance with shortness of breath, and burning pain in the posterior gluteal region. He was admitted to the hospital that night. Bryan received a red blood cell transfusion, and the calcium level was treated with IV hydration and Zometa. Bryan underwent a bone marrow biopsy the next day and was diagnosed with IgA multiple myeloma—stage III with high-risk cytogenetics. Bryan: I knew right away that this was not going to be an easy version of myeloma to treat, because it wasn’t the standard IgG with simple cytogenetics, I was an IgA with high-risk cytogenetics.

Multiple myeloma is a cancer of the plasma cells. The disease belongs to a spectrum of disorders referred to as “plasma cell dyscrasias.” Plasma cells are made of B cells, a type of white cell that is present in the bone marrow. Healthy plasma cells make proteins called “antibodies,” which help fight infection. Myeloma develops when a plasma cell is changed (mutated). The change in the cell is caused by one or more acquired genetic mutations. The changed plasma cell (myeloma cell) multiplies, and the cells continue to grow in the marrow and crowd out the healthy plasma cells. They also crowd out healthy white cells, red cells, and platelets. Bryan started treatment right away with Lenalidomide, Bortezomib, and dexamethasone (RVD). He was discharged after about a week and started with outpatient treatments of RVD (Table 5.1). Lenalidomide’s exact mechanism of action on cancer cells is not clear. It may act by inhibiting the growth of new blood vessels (angiogenesis) in tumors, enhancing

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Table 5.1  Induction chemotherapy Lenalidomide, bortezomib, and dexamethasone (RVD) regimen R-Lenalidomide 5 mg to 25 mg PO V-Bortezomib 1.3 mg/m2 IV D-dexamethasone 40 mg PO Cycle every 21 days

the status of the immune system, or decreasing cytokine and growth factor production. Bortezomib targets and inhibits the proteasome enzyme complex within the cell. Proteasome is part of the cellular machinery and has many functions within the cell, such as it helps to control the level of many of the proteins that help regulate cell division and cell survival. By interfering with its function, this can lead to apoptosis (cell suicide). Dexamethasone is classified as a corticosteroid (more precisely a glucocorticosteroid) and has many uses in the treatment of cancer. One way that it works is to decrease inflammation. Taking advantage of the anti-inflammatory properties of the medication, corticosteroids are used to decrease the swelling around tumors. For example, by decreasing swelling around tumors in the spine, brain, or bone, it can decrease the pressure of the tumor on nerve endings and relieve pain or other symptoms caused by the pressing tumor. In addition, it is thought that corticosteroids may help in the treatment of patients with blood disorders, such as multiple myeloma. Corticosteroids may work by causing programmed cell death (apoptosis) of certain cells, which may help to fight the disease. Bryan: My diagnosis significantly affected my life, it totally blew it up, I was working, I was very active coaching, taking care of our animals in the barn, plowing the driveway, and exercising. I retired due to the diagnosis, and I continue to struggle with fatigue, weakness, and peripheral neuropathy daily. Natalie: I was already scheduled to retire two weeks after Bryan’s diagnosis, I honestly cannot fathom how people can be a caregiver and work full time. I totally went about face; I went from working 120% to not working at all. I was focusing on his treatment and recovery and being a full-time caregiver.”

Bryan completed 4 cycles of lenalidomide/bortezomib and prednisone (RVD). He experienced side effects of peripheral neuropathy from bortezomib, so it was stopped. He continued with lenalidomide and dexamethasone. Bryan’s treatment was complicated with several episodes of atrial fibrillation that required emergency room visits and admissions. He also experienced peripheral neuropathy affecting his hands and feet, left foot drop, and severe gluteal pain with muscle spasms. Bryan was followed by palliative care from the beginning of his diagnosis. They were instrumental with symptom management. They recommended oxycodone as needed for pain and valium at bedtime to help with sleep, as his pain keeps him awake at night and he continued with neurontin for peripheral neuropathy. Pain was a major contributor to Bryan’s difficult time; this makes him feel

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frustrated, and at times he takes this out on those around him. Palliative care counseled Bryan and his family ways to identify when he is getting irritable toward them. He also expressed having a hard time transitioning to the role of a patient as opposed to his role of a physician; he found this very challenging. Bryan and Natalie went to DFCI for a second opinion for transplant, which left them with lingering questions that they hoped would be resolved related to different perspectives on options for transplant, especially on timing. Bryan and Natalie understood the intricacies of his disease and treatment. They were hoping the two transplant hematologists would review the prior bone marrow results and would agree on how to proceed with treatment and transplant timing. Bryan and Natalie were planning a family trip prior to his transplant to the Galapagos Islands off the shores of Ecuador. He wanted one more family trip prior to his transplant admission. Bryan’s bone marrow biopsy after 4 cycles of RVD showed no evidence of disease, so the plan was to move forward with Cytoxan and G-CSF mobilization in September, then collection of stem cells to follow 12 days later. He tolerated the mobilization and cell collection with no complications. Bryan was admitted in October for his autologous stem cell transplant with melphalan conditioning (Table 5.2). Bryan felt prepared for admission. Bryan: I don’t know how I could have been better prepared except I was scared to death; my worst fear was that the transplant would not work. Natalie: I felt having one transplant coordinator nurse identified, as your go to person is really a great thing, it just felt like she was totally there for us to answer any questions or deal with any problems, it was thorough and perfect. My biggest fears of transplant were complications such as infection and failure to engraft.

Bryan started his melphalan conditioning regimen upon admission on Day −2. Table 5.2  Autologous stem cell transplant, conditioned with high-dose melphalan Day −2 Line placed Admit IVF 500 cc/ hr. – 2 hrs prior to chemo Orders checked by 2 BMT RNs Pre-meds Oral ice therapy 1 bag administered over 30 minutes

Day −1 Time/ number of bags for stem cell infusion verified with cellular therapy

Day 0 Early review of the stem cell infusion checklist 4 hours of IV hydration prior to stem cell infusion Pre-­ medication Administer frozen stem cells

Day +1 4 hours IV hydration

Day +2 4 hours IV hydration

Day +3 Rest

Day +4 Rest

Day +5 Zarxio starts

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Natalie spent most nights with Bryan while he was in the hospital; Bryan felt more secure when she was with him. Bryan: There were times when I really did not want to be alone and thankfully my family helped me in this regard. When I realized how weak I was becoming, there were times I could not imagine ever getting strong enough to do anything.

Natalie had a lot of support at home taking care of the animals and running errands and cleaning the house prior to Bryan’s discharge to home. Natalie: It was hard watching him be so debilitated, I was thankful for the visitors, it helped spending time interacting with people, doing puzzles, and reading.

The room was decorated with family photos and Natalie put bird feeders outside the window. When Bryan felt strong enough, he and Natalie walked outside to enjoy the fall weather. Bryan: It was wonderful to be on the ground floor, with access to walking outside, I remember pushing to get some exercise every day, I remember trying to do the stave puzzles with great effort and listening to books on tape somewhat successfully.

Bryan was very grateful to the patient support services that were available during his inpatient stay. He utilized creative writing, music, and massage therapy: “It was wonderful, I wish I could have had more massages. Marv from creative writing was a wonderful writing inspiration, storytelling inspiration and support.” Bryan continued writing and composing poems during his inpatient stay; he wrote the poems “1000” and “Harvest” because he was the 1000 patient to receive a stem cell transplant at the medical center. He was ready for discharge after 14 days and he insisted on going to the annual event of “patients telling their stories” on the way out of the hospital. Bryan: I was exhausted during the annual event of patients telling their stories, hosted by Marv. It was truly great to be there although I was completely exhausted and wondered how I was going to get through the entire event and read my poem. I don’t really think I appreciated how debilitating the transplant was going to be, even though I was warned. I don’t think you can prepare someone for how crappy they are going to feel. Just prior to discharge, I was told I would have about 20% of my normal energy and it would decline to about 10% over the first week, I did not believe the physician, but I should have. I knew that I had such good support at home and that was comforting. I knew I was lucky to be getting out of the hospital in only two weeks and that everything had gone so smoothly.

Bryan and Natalie both recognized upon discharge, even with all the support at home, it was still a little unnerving to leave the hospital where they had 24-hour care and support. Natalie: After discharge from the hospital, taking care of Bryan was all-consuming. I was able to go out for walks, but my fitness declined. After a lifetime of working, it was a gift to be able to spend time together and to encourage him.

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It really struck home with Bryan, after the first day home from the hospital, how much he really appreciated the nursing staff. He did not want to overburden Natalie at home; he remembers, “I wanted oatmeal, so I crawled out of bed and filled the pot full of water and placed it on the stove to boil, then I had to lie down. I got up again, went and got the oatmeal out of the cupboard and added the oatmeal to the boiling water and had to go lie down again.” Bryan expressed how grateful and lucky he felt to live so close to the medical center because he had multiple appointments after discharge. Bryan: Having to go back in so frequently to get IV electrolytes, fluids and red blood cells transfusions felt like a major travel. The staff in the infusion suite and the coordination with my oncology team was very, very good. For the first month to six weeks, being on house arrest was not a problem, as I had little energy to do anything else. Being home and being able to walk outside was incredibly helpful. There are many silver linings I have discovered as I was forced to just slow down, having to sit around and admire my gardens, land and barn was a totally different experience and wonderful, I think that’s a lot of where my writing came from.

Bryan struggled with normalcy post-transplant and what that now looked like for him: “for me there’s sort of two elements, element one is practical, how do you navigate the logistics of neediness and relationship issues, in this new context. The other element is more of an existential, how do you extract the most out of your life you’re living right now to make it feel it’s the most worthwhile and the best part of your life.” Autologous stem cell transplant for multiple myeloma is used to help provide significant remission that is both long and deep, extending survival. Bryan was aware of his own disease and the poor distinct characteristics, which led him to many feelings and thoughts of his disease: I’ve gotten discouraged and scared of the future sometimes. I know the disease is silent and you have no control at all and that’s a really different animal. The disease is lurking there, it is a visitor that I really don’t want, so hopefully I can keep him or her locked up in a closet for a little while longer. I don’t know what is going to happen when the next shoe drops and the myeloma comes back which I know it’s going to, eventually. Now that I feel better it is increasingly important for me to not let the myeloma distract me from my current life and well-being, that is a big challenge.

Bryan started monthly treatments of Elotuzumab post-transplant to help minimize disease progression. Bryan: I see myself as having a chronic illness. I am not at full strength. I am immunocompromised on chemotherapy. My brain does not work as well as it used to with remembering names and sometimes words, but it is okay. I have found new things that I enjoy greatly that I didn’t have time or take the time to enjoy pre-diagnosis. So my limitations are frustrating at times and perhaps a gift at times as well. Writing, singing, not rushing, participating in teaching and other causes important to me, this helps counterbalance my sense of loss of my health. I realize that myeloma is not curable. I know that my disease genetics are not the best, so this disease is part of my life. I fight every day to avoid it taking over my life. Natalie: Bryan has recovered so well and looks great that it’s difficult sometimes to remember that he has ongoing immunosuppression and a chronic illness. I have to make

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J. Gentes myself more vigilant to avoid exposure to infection. Otherwise, it’s wonderful to not regard him as ill and to enjoy each day. I really took to heart, make the most of everything and everyday, maybe it is my optimism coming through and not wanting to waste time and focus on living in the moment.

Bryan reflected: “I am no longer invincible in any way (however misguided that belief was before), I have limits that I can’t anticipate very well still although they are better now. I appreciate more than I could ever imagine how much friends and connections mean to me.” Natalie and Bryan both expressed how important palliative care had been to them throughout their journey. They have been followed by palliative care since the beginning of diagnosis for pain management but the team quickly became more than that. They also helped with the emotional stress of the serious illness of cancer and the toll it has on the entire family. The palliative care team helped facilitate the management of anxiety and helped them gain the strength to carry on with daily life and improve the quality of life. Natalie recalled when the palliative care team helped Bryan with the “issue of time, he was feeling like he can’t waste anything and everyday is important and he was very anxious to push things along. It was very helpful to talk to palliative care, they suggested Bryan make a list of priorities for himself and the two of us together, then figure out what is important. They also emphasized that now Bryan and I are now home together all the time, we need to figure out how much time together is going to make us crazy. We need to find the balance of time together and alone time to pursue our own interests, it has been great talking that out.” Bone marrow transplant is an especially unique treatment, where patients have “high-risk” disease, but also have the capability to undergo high-dose chemotherapy and the re-infusion of stem cells. This treatment also comes with high risks for complications and even death, which is reviewed with each patient and caregiver. Unfortunately, Bryan lost his battle with multiple myeloma on August 29, 2019, three years after his autologous stem cell transplant. Bryan’s memory lives on through his family, his poetry, and all of the students he taught and coached through crew. Bryan was the coach for the Hanover crew for 14 seasons. He wrote over 400 poems, 50 of them published in a book of poetry “Spaces in Between.” Bryan touched many lives and taught many about living and appreciating the little things and the art of taking nothing for granted.

Sources Consulted Badros A, et al. Autologous stem cell transplantation in elderly multiple myeloma patients over the age of 70 years. Br J Haematol. 2001a;114(3):600–7. https://doi.org/10.1046/j.1365-­2141 .2001.02976.x. Badros A, et  al. Results of autologous stem cell transplant in multiple myeloma patients with renal failure. Br J Haematol. 2001b;114(4):822–9. https://doi.org/10.1046/j.1365-­2141.2001 .03033.x.

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Dimopoulos MA, et al. Renal impairment in patients with multiple myeloma: a consensus statement on behalf of the International Myeloma Working Group. J Clin Oncol. 2010;28(33):4976–84. https://doi.org/10.1200/JCO.2010.30.8791. Kumar SK, et al. Bortezomib, dexamethasone, cyclophosphamide and lenalidomide combination for newly diagnosed multiple myeloma: phase 1 results from the multicenter EVOLUTION study. Leukemia. 2010;24(7):1350–6. https://doi.org/10.1038/leu.2010.116. Moreau P, et  al. Comparison of 200 mg/m(2) melphalan and 8  Gy total body irradiation plus 140 mg/m(2) melphalan as conditioning regimens for peripheral blood stem cell transplantation in patients with newly diagnosed multiple myeloma: final analysis of the Intergroupe Francophone du Myélome 9502 randomized trial. Blood. 2002;99(3):731–5. https://doi. org/10.1182/blood.v99.3.731. Tomblyn M, et  al. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant. 2009;15(10):1143–238. https://doi.org/10.1016/j.bbmt.2009.06.019.

Part II The Allogeneic Stem Cell Transplant Journey

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Saving Superman Sara Cooke

Alicia Brown Photograph

The cyclist pictured managed to keep a positive attitude and strong fight while enduring treatment and eventual stem cell transplant for Acute Myeloid Leukemia. This photo was taken on the second anniversary of his transplant, while on an incredible two-day journey of cycling the length of NH (Canadian to Massachusetts border). He insisted on making the inpatient oncology unit his stopping point after the first 150 miles—a chance to say thank you to the people who saved his life, a S. Cooke (*) Transplant and Cellular Therapy, Dartmouth Health, Lebanon, NH, USA e-mail: [email protected] © The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 J. Coffey et al. (eds.), Patients’ Lived Experiences During the Transplant and Cellular Therapy Journey, https://doi.org/10.1007/978-3-031-25602-8_6

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chance to reflect on his journey to “the other side” of these hospital doors and his life post-cancer.



MAN CUT FROM IRON Raleigh Ormerod

I am the Man Cut From Iron. When you hear the cold winds blow, Remember where the colds winds go for comfort: They come to me, for I am the Man Cut From Iron. The groans you hear in the dark of the night: That’s just me resting up for another fight, for I am the Man Cut From Iron. Of all that’s been won, said or done, Whether finished, or just begun, It comes through me, for I am the Man Cut From Iron. Colin: “You know people get cancer, they go through treatments, but you never think it would happen to you.”

Colin, a 36-year-old male, presented to his primary care physician with increasing fatigue, particularly over the last two months. Colin is an avid athlete and has devoted his life to fitness. He works as a physical trainer and spends his free time participating in half marathons, iron man competitions, and century rides. He has a wife named Alannah and together they have two young girls, 18 months and 5 years old. Alannah: “About a week prior to Colin’s diagnosis we were out for a family run. He and I were training for a half marathon … he was pushing the stroller and he two weeks prior could run 3 miles … and he couldn’t run for more than 30 seconds and had severe cramping in his calves. Huh? That’s kind of weird. Well maybe you’re tired, you are working 3 jobs right now, so maybe that’s part of it. But then he was really out of breath … it was a Monday, he was really not feeling well and he was starting to look kind of gray, ashen, so we said alright call the primary.”

Colin went to his PCP and had labs drawn; within 24 hours of having his labs drawn, he was admitted to the inpatient hematology/oncology unit. Colin: “It was literally 24 hours from the time that I had my bloodwork done until I was up here for what I call my hotel stay …. I had no time to prepare. I didn’t even have a bag packed. The first thing I thought of was, ‘Here it is.’ I thought of all my girls.”

Colin had his first of many bone marrow biopsies the following day. His biopsy showed a normocellular marrow with extensive infiltration by acute myeloid leukemia (AML) with approximately 70% blasts. AML is a type of cancer that originates in the bone marrow. Normal myeloid cells can become white blood cells, red blood cells, or platelets. In AML, a mutation

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occurs that stops the normal development of these myeloid cells and leads to the overdevelopment of immature white blood cells (blast cells) that are not able to function normally. These blast cells can then overwhelm the bone marrow, blocking the normal, healthy cells. AML does not just affect the blood and bone marrow; it can also spread into the lymph nodes, central nervous system (CNS), spleen, liver, and testicles. Induction with 7 & 3 (daunorubicin and cytarabine) was started the day after Colin’s admission (Table 6.1). A repeat bone marrow biopsy is typically obtained on Day 14 from the start of chemotherapy to assess its effectiveness (hopefully clearance of all blasts). Colin’s bone marrow showed residual blasts (49%) consistent with residual disease. This was disappointing news, meaning re-induction, or a second round of chemotherapy, was necessary. Colin: “I was afraid that it wouldn’t work. I was afraid of letting my girls down. I was afraid of letting Alannah down if I didn’t fight hard enough.” Alannah: “It was so hard leaving him Sunday afternoons, going back home, relieving either of the girls’ grandmothers who had been caring for them throughout the weekend, going back to work for the week, all while supporting MY patients and putting on a brave face. It sucked! But we did it-skyped with the girls every night so they could see their dad, talked multiple times a day so I knew what was going on, put lists together of more decorations to bring up to the hospital since we knew it would be an even longer haul.” Colin: “I was a pretty staple person on 1 West. I would do my best to stay active and go out for my walks … for me personally, I really didn’t have to do anything ‘cause I just laid in the bed and they just put stuff in me. I laid there and watched TV. It was all Alannah doing everything. I would say (she) took the most of it. I would say for me I would, just I couldn’t do anything. I was up here. I wasn’t able to go home. I wasn’t able to work. I wasn’t able to do anything so it was just kind of waking up seeing what they (the doctors) say and what the nurses do.”

Colin underwent re-induction with ME (mitoxantrone and etoposide) (Table 6.2). His Day 14 bone marrow biopsy showed a hypocellular marrow with autologous transplant), certain chemotherapies used in the conditioning regimen, poor performance status, and undergoing a second transplant. Prevention is key, as VOD is difficult to treat once it develops. Colin remained on Lovenox and ursodiol for prophylaxis until discharged. Colin also started Pneumocystis jirovecii pneumonia (PJP) prophylaxis on the day of admission due to the increased risk that transplant places patients at for this particular type of pneumonia. Colin was placed on Bactrim (Trimethoprim-­ Sulfamethoxazole) from Day −8 through Day −2, then again on Day +30. Bactrim was held in between, due to its potential for count suppression that might impede engraftment (the recovery of the bone marrow after transplant). Colin remained on Bactrim after Day +30 until 6 months after the discontinuation of all immunosuppressive medications. Colin: “I knew it was going to be hard but I didn’t really fully understand how hard it was going to be. Feeling completely drained, completely wiped out and nauseous all the time. It wasn’t just … bouts of this and that, it was from the time I woke up to the time I went to bed. It was completely exhausting. The more chemo treatments I got, it got a lot harder … especially the nausea.”

During his transplant conditioning, Colin struggled with nausea/vomiting, epistaxis (nose bleeds), constipation, and weight gain/fluid retention requiring diuretics and multiple antiemetic medications to control nausea. Oxymetazoline nasal spray was used to minimize epistaxis episodes. A consultation with an ear/nose and throat (ENT) provider was performed; no intervention was recommended at the time; his epistaxis was believed to be due to dry air. Platelets were adequate. Colin was unable to tolerate the oral Supersaturated Calcium Phosphate Rise (Caphosol) used for mucositis prophylaxis because it made him nauseous. He refused the Caphosol and used a different dry mouth rinse instead. A baseline EKG and urinalysis (UA) were obtained prior to cyclophosphamide administration on Day −3. Both an EKG and a UA were repeated prior to his next dose of cyclophosphamide on Day −2. Physician approval of the EKG is required

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on both days prior to administration of the cyclophosphamide in case any cardiac changes are noted. Colin started taking cyclosporine, an immunosuppressant used to prevent graft-­ versus-­host disease (GVHD) on Day −1. Common side effects of cyclosporine are headache, high blood pressure, nausea/vomiting, diarrhea, tremor, dizziness, and flushing. To maintain therapeutic levels of cyclosporine and minimize adverse reactions, trough levels are drawn twice a week while inpatient and weekly in the outpatient setting. The first trough level is drawn on Day +2. The trough level is considered therapeutic for cyclosporine if it is between 200–400 ng/mL, with the goal being close to 250–300 ng/mL. Day −1 is utilized as a rest day, allowing washout of chemotherapy prior to the infusion of stem cells on Day 0. The day was spent educating Colin on the stem cell infusion tomorrow, coordinating the time of the infusion with cellular therapy, and allowing him some time to walk around the hospital/outside with his wife. For Colin’s regimen, there must be a minimum of 36 h between the last dose of chemotherapy and his stem cell infusion. The nurse taking care of Colin on Day −1 is responsible for confirming this prior to calling cellular therapy. This was the last day Colin was able to leave his room. His regimen restricted him to his room starting on Day 0 until his ANC was >500. Colin: “Not being able to leave the room, that was mentally, that was the most challenging part …. Knowing that I couldn’t go past that little line in the door was pretty horrific..”

Colin, wearing a Superman shirt, received two syringes of his brother’s peripheral stem cells. He was monitored closely with each syringe administered for any signs of a reaction related to the solution in which the stem cells are preserved, called dimethylsulfoxide (DMSO). His vital signs were taken every 5 minutes during the infusion. Colin experienced flushing of his ears, which resolved at the end of the infusion. No interventions were required. This is considered a “non-reaction” and an expected side effect from the DMSO (Table 6.5). Alannah: “I have to admit, yes, it is rather anticlimactic. But watching the cells thaw on their “hot dog steamer” and watching the entire process was truly amazing. Colin, as usual, was his positive self, even giving the camera a thumbs up, ready for this to be the beginning of the end of “kicking cancer’s ass,” as he would say.”

Over the next few days, Colin’s biggest complaint was nausea. He required a hyoscine (Scopolamine) patch, scheduled prochlorperazine, and as needed Table 6.5  Plan of care outline on Colin’s whiteboard for Day 0 Action Pre-hydration Pre-medications

Time 1000 1330

Stem cell infusion Post-hydration

1400 1440

Duration NS @ 250 ml/hr for 4 hrs Tylenol 650 mg Benadryl 50 mg Colin received 2 syringes NS @ 250 ml/hr for 2hrs

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promethazine, lorazepam, and ondansetron were given. He also began to complain of increased fatigue as well as a poor appetite. Colin: “That was the worst part, you know, losing my taste. I love food so that was awful. Everything that was cooked tasted burnt and everything that was sweet tasted like I was eating spoonfuls of sugar. It totally changed my taste buds … it continued on quite a while after that. It wasn’t just for the hospital stay, it was a month after that.”

By day +5, Colin complained of a “scratchy” throat and required an IV fluid bolus for poor oral intake. On day +6, Colin experienced repeated episodes of epistaxis, requiring the use of oxymetazoline HCl (Afrin) nasal spray and 2 platelet transfusions. Colin also began to feel increasingly fatigued and mildly SOB with exertion. It was also becoming increasingly painful to swallow. Colin: “I got the first bloody nose of my life; it lasted 7 hours. It was so bad that I needed a blood transfusion … it just kept going and going and going.”

Day +7 Colin was started on a hydromorphone patient controlled analgesia pump (PCA) due to his mucositis/esophagitis pain. He was also placed on continuous IVF at 100 mL/hr for poor oral intake. The following day, Colin required an increase in his PCA settings to include a continuous dose of hydromorphone. He was unable to tolerate any oral intake. He was also becoming constipated from the opioid use and was started on a bowel medication regimen. According to nursing documentation, Colin was lethargic and weak. He refused to get out of bed even to sit in the chair. Colin: “I’ve never experienced that type of trauma, I guess you would call it trauma, to my body where it’s fighting as hard as it can. When you feel awful all the time.”

Colin experienced a neutropenic fever on Day +9. His temperature was 38.8  °C.  Blood cultures, a urinalysis with reflex culture, and chest x-ray were obtained. He was started on antibiotic therapy. He continued to complain of overwhelming fatigue and again refused to get out of bed. Alannah: “The actual transplant was the easy part. The after effects quickly kicked in as he developed mucositis. The next two weeks were about as hard for me as coping with his neutropenic fever. There were entire days I wasn’t able to talk to him….he wouldn’t answer his phone or even text. Even when I would spend the weekend, he would insist on the lights being off in the room, the TV off, no music, just lying in the fetal position …. I knew he was in pain and there was nothing I could do to help.”

Colin’s ANC bumped up to 140 on day +11. His prior neutropenic fever workup came back negative. He continued to complain of mucositis pain. His oral intake remained poor, but his weight was increasing above baseline, so his IVF was slowed down to 50mL/hr. His nausea began to kick back in, and Colin believed it to be related to when he used his PCA. Finally, Colin was able to leave his room on day +12 when his ANC reached 540.

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On day +13, Colin’s PCA was stopped, and he was able to tolerate PO hydromorphone with IV breakthrough to manage his mucositis pain. This was the first post-­ transplant day Colin felt strong enough to ambulate off the unit. The following day, Day +14, Colin began to have diarrhea, a Clostridium difficile sample was sent and resulted negative. His tunneled line was removed, and he was able to tolerate oral medications. Colin continued to be fatigued though and slept the majority of the afternoon. Discharge teaching was reviewed by the nurse with Alannah over the phone. On day +17, Colin was discharged from the hospital with close follow-up. He was sent home with PO magnesium due to his daily requirements during transplant. Low magnesium levels are usually related to magnesium wasting through the kidneys caused by cyclosporine or tacrolimus. He remained on cyclosporine, acyclovir, and fluconazole prophylaxis. Alannah: “He was so excited to get home in time for Halloween and see our girls get all dressed up! However, he was nervous this time, and so was I. I had prepped the house like I had been instructed, I knew about all of his medications, what to do in case of another neutropenic fever, how to help him. This time was different though. He was so much sicker. There were days and even weeks he wouldn’t eat anything, would barely drink anything. He had lost more weight and there was nothing I could do to help. He was grumpy, frustrated with how he felt.”

Once home, Colin slowly began to return to his normal self. Fatigue, nausea, and vomiting continued to be his major complaints. Colin: “I was not prepared for the few months post-transplant. I knew it was going to be a hard recovery but I had no idea it would be as difficult as it was. The constant nausea, no appetite, no energy. Not being able to move off the couch or get out of bed was absolutely horrible. … When I was home immediately after transplant it was nothing out of the ordinary to wake up at 7/7:30, go lay on the couch and then get off the couch just to use the bathroom and then when my wife got home. So I would be in the fetal position all day long not being able to eat, keep anything down, it was like clock-work, 10:15 in the morning I would get sick, 2:15 in the afternoon I would get sick, and then around 7:30 I would get sick again. I ended up losing 40 pounds.”

Alannah observed: Alannah: “He no longer had to put on a show for anybody and he can be in his pajamas on the couch all day and feeling like crap. I don’t think I was emotionally prepared for him coming home and not kind of picking up where he left off before transplant. A month later and he’s a third child if nothing else. If nothing else, he’s the child I have to take care of the most and devote the most attention to. It’s that unexpected piece that you feel like your family member is home but your patient is home. You’re willing to take care of him absolutely, but how do you even do that? You’ve taken care of the house, you know all the housekeeping and all the stuff you’re supposed to do but what the heck do you do with somebody who refuses to eat and drink?”

On Day +52 Colin developed a generalized maculopapular rash, mainly on his upper body and legs. His nausea also continued. This was concerning for acute

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GVHD, so Colin was started on PO prednisone and budesonide. Within a week, his rash, nausea, and energy had all improved. Colin started on a prednisone taper on Day +64 with good success. Due to the resolution of nausea and vomiting with the implementation of steroids, it was presumed that Colin had manifested gastrointestinal GVHD, as well. GVHD is an immune reaction between the donor’s T cells and host tissue that may occur after an allogeneic transplant. It occurs when donor cells (graft) recognize the patient’s body (host) as foreign and launch an attack in the form of an immune response. There are two main types of GVHD, acute and chronic. Acute GVHD usually develops within the first few months after transplant, although it can develop later in some cases. The organs targeted by acute GVHD are the skin, liver, and gastrointestinal tract. Chronic GVHD occurs later on in the transplant course, at least 3 months after transplant. Unlike acute GVHD, chronic GVHD can affect any organ system in the body, including joints and fascia. Slowly, Colin began to return to his more positive and active self. He began exercising again and being more interactive with his daughters. Colin: “Always stay positive. Have a smile on, even if you have to force that smile …. Have fun. Do something ... whatever you need to do to make yourself comfortable. But never leave that positive thought. Once you do, once you get down, especially when you’re going through treatment, especially if it’s a transplant … your body is going to shut down. So always know you need to fight the hardest and just keep that positive attitude towards it and hopefully you’ll come out on the right end.”

His Day +119 bone marrow biopsy showed 90% donor chimerism. Chimerism is defined as the presence of cells from two different individuals. A chimerism determines the percentage of donor cells vs. recipient cells in the patient’s lymphoid and myeloid cell lines. The higher the chimerism, the more donor cells are present in comparison to the recipient; after allogeneic transplant, full donor chimerism is the goal. Following stem cell transplantation, chimerism analysis is checked routinely starting around Day +30 and then at various milestones. On Day +141 Colin was started on a cyclosporine taper and his prednisone was stopped. His cyclosporine taper was completed by the spring of 2016. By this point, Colin was feeling good and getting back into his normal life. He was back to performing yard work and biking in his free time. By June, Colin was allowed to start working again and was in the process of training for a century ride to raise money for cancer research. He was able to bike 100 miles that year. According to Alannah, that began Colin’s return to fitness. By November, Colin was back to running half marathons. Colin was diagnosed with oral and ocular GVHD over the next few months. His oral GVHD was treated with an oral steroid rinse called clobetasol. His ocular GVHD required a tear duct plugging and cyclosporine eye drops to relieve his dry eye symptoms. Occasionally, Colin has minor symptoms such as dry, irritated eyes or the occasional mouth sore, but he says they only last for a day or two before going away.

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On his second “new birthday” Colin rode his bike the entire length of New Hampshire, a total of 238 miles over two days, to raise awareness and funding to purchase exercise equipment for future transplant patients to help maintain their strength during their transplant journey. Colin finished the first 150 miles of the ride at the inpatient unit where he received his transplant. The nurses gathered at the door to greet him with a Superman cape to show their support. A picture of Colin in front of the hospital doors, engulfed in mist, now hangs on the wall in the inpatient unit to inspire other patients. Alannah: “The greatest accomplishment is his ability to have his sense of humor, enjoying rolling on the ground, playing with our girls, and laughing and crying together for a family movie night. Amazingly, he’s still the same Colin as he was in the summer of 2015, but an even stronger version.”

At this point Colin was back to his normal self. He was back to work as a physical trainer and working towards becoming an American College of Sport Medicine/ American Cancer Society Certified Cancer Exercise Trainer. Colin’s story serves as an inspiration to all—a real-life Superman. Colin: “I see myself as being stronger …. I don’t want people to see me as being any different than I was before diagnosis. If they do, hopefully it would be that they see me as an inspiration to other patients.”

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Brothers in Arms Lisa Wesinger

Sisters ~ Melissa West Mixed Media Coming from the same roots, sharing the same strong heart, coming together as one strong force of life.

L. Wesinger (*) Transplant and Cellular Therapy, Dartmouth Health, Lebanon, NH, USA © The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 J. Coffey et al. (eds.), Patients’ Lived Experiences During the Transplant and Cellular Therapy Journey, https://doi.org/10.1007/978-3-031-25602-8_7

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REVELATION Melissa Post At first Fear grew as large as I would let it. I tried to wrap it around me like a cloak. “Protect me”, I asked. Its crushing weight Suffocated me. It didn’t protect me. “Be in the moment”, I countered. I felt like a figurehead, Standing on the front of a convertible Traveling ninety miles an hour. The cloak went flying off. So did my clothes, piece by piece. There I was – Just me – Standing upright in the wind.

“My Brother to my left, My Brother to my right, Together we stand, Together we fight.” (unknown author) Ryan: Before I became ill, I was very athletic, playing football, basketball, and taking part in any outdoor activity I could. I was an active firefighter. After becoming sick, I did not have much energy or strength and had to always try to avoid places that could put me at risk of an infection; places like fairs (because of the animals) and restaurant buffets. I worked at the police department as a dispatcher but I was literally falling asleep at the desk in the middle of the day. I also worked as a landscaper but I could no longer be near fresh cut grass or anything that involved dust. Being at the hospital 3 times a week I couldn’t really do much of anything, so pretty much my normal life just stopped completely.

Since Ryan was a teenager, he knew he wanted to be a firefighter. At 14 years old, he joined the local fire department as an Explorer. The Explorer program provides teenagers with an interest in Fire Services the ability to learn more about the job and the opportunity to start building the skills necessary to succeed. Ryan not only gained firefighting skills, he was adopted into a family of men and women who would forever be a part of his life and survivorship. At 19, Ryan was a strong, active, witty, volunteer firefighter who had just started a job at Walmart, when he presented to a community hospital with complaints of shortness of breath on exertion, bleeding from his mouth and nose, easy bruising, low grade fevers, and a 15-pound weight loss. Initial workup revealed he was

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pancytopenic (low red, white, and platelet blood counts) and was transferred to a major medical center over 1 h away. Ryan was given an antibiotic for a peritonsillar infection and his symptoms rapidly resolved. A bone marrow biopsy was performed and Ryan was diagnosed with severe aplastic anemia (SAA). Aplastic anemia (AA) is not cancer, but rather a life-­ threatening form of bone marrow failure which, if untreated, is associated with very high mortality. AA refers to pancytopenia in association with bone marrow hypoplasia/aplasia (little or no red, white or platelet cell production), most often due to immune injury to the multipotent hematopoietic stem cells. The term “aplastic anemia” is a misnomer because the disorder is characterized by pancytopenia, including low white blood cell and platelet count, rather than anemia alone. The low WBC count puts patients at high risk for infection, and low platelets predispose them to bleeding. Ryan: I woke up one morning in March feeling terrible and bleeding from my mouth. I went to the local emergency room … after getting blood work back I was sent to a comprehensive cancer center, where I was admitted … I was diagnosed with severe aplastic anemia (SAA). I was hospitalized for three weeks receiving blood products and antibiotic therapy for a throat infection. After discharge, I received blood products a few times a week while taking medication for my SAA.

Two weeks later Ryan was readmitted with a right lower extremity cellulitis infection that was treated with the antibiotic vancomycin. Ten days later he had a central venous access device (mediport) placed and was admitted to begin immunosuppressive treatment with anti-thymocyte globulin (ATG) and cyclosporine (CSA) therapy. This hospitalization was complicated by serum sickness secondary to the ATG. Serum sickness is an immune response that’s similar to an allergic reaction. It happens when antigens (substances that trigger an immune response) in certain medications and antiserums cause your immune system to react. The antigens involved in serum sickness are proteins from nonhuman sources. Ryan also experienced two additional complications; a Staphylococcus epidermidis mediport infection, and Clostridium difficile colitis (bowel infection). Due to the infection, the mediport was removed. Over the next year, Ryan was transfusion dependent, receiving platelet transfusions 2–3 times per week and packed red blood cells (PRBCs) 1–2 times per week (Table 7.1). Ryan: The doctors told me many times that having people help me was vital in order to fight this disease ... I felt like I was alone most of the time … When I was first diagnosed my older brother, Thomas, left school and moved back home. Even though he was busy starting his new career as a firefighter and he only had a few months of school left, he

Table 7.1  Induction chemotherapy, IST Immunosuppressive therapy (IST) ATG antithymocyte globulin horse (ATGh)40 mg/kg/d × 4 days CSA cyclosporine 12 mg/kg/day

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L. Wesinger decided to commute to school so that he could drive me to my appointments and help me in any way possible. He was my only support. My parents weren’t involved at all. (Ryan’s parents had long-standing mental illnesses.)

Ultimately, Ryan’s trial of immunosuppressive therapy (IST), the ATG, and CSA, with growth factor support, proved unsuccessful. Fourteen months after his diagnosis, a bone marrow biopsy was performed, and the results were consistent with persistent aplastic anemia. The next step and only potentially curative therapy for Ryan’s SAA was an allogeneic stem cell transplant. This required first finding a genetically suitable HLA matched donor. A list of potential related donors was obtained while simultaneously seeking a potential 10/10 matched unrelated donor through the National Marrow Donor Program (NMDP) Be the Match Registry. The NMDP has over 22 million selfless volunteers worldwide who stand ready to be a life-saving blood and marrow donor. Human leukocyte antigen (HLA) typing is complex. There are many HLA markers: Half are inherited from the mother and half from the father, so each brother and sister who shares the same parents as you has a 25% chance (1 in 4) of being a close HLA match. Extended family members are not likely to be close HLA matches. Overall, about 70% (7 out of 10) of patients who need a transplant will not have a fully HLA matched donor in their family. Research has found that a donor must match at the six major histocompatibility complex (MHC) loci (two alleles at each locus). The remaining sites are called “minor” histocompatibility loci, where matching is not as crucial. The best match is found through detailed testing. Because some HLA types are more common than others, some patients may face a greater challenge in finding a matched donor. Some HLA types are limited to certain racial and ethnic groups, so the challenge of finding a matched donor may be especially high for patients of ethnic minorities. HLA matching is vital to transplant. A close match between a donor’s and a patient’s HLA markers is essential for a successful transplant outcome. HLA matching promotes the growth and development of new healthy blood cells (called engraftment) and reduces the risk of both graft rejection and a post-transplant complication called graft-­versus-­host disease (GVHD), where incoming donor T cells attack the recipients’ (patients’) own tissue. The most commonly affected organs are the skin (rash), gastrointestinal (GI) tract (diarrhea), and liver (hyperbilirubinemia). The incidence of GVHD in allogeneic transplant recipients is 30–60%. Risk is increased when the donor is not a 6/6 HLA antigen match or when an unrelated donor is used. Ryan’s only sibling, his brother Thomas, submitted an HLA cheek (buccal) swab kit to the American Red Cross for analysis. Within 5 days, it was determined that Thomas was not a match. A search for a 10/10 fully matched unrelated donor was initiated through the NMDP.  Originally Ryan was matched with five possible donors. However, four were ruled unsuitable and the fifth had recently received a tattoo. Fortunately, a 10/10 HLA fully matched international donor was eventually found.

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Ryan was admitted for a matched unrelated donor (MUD) allogeneic stem cell transplant with cyclophosphamide (Cytoxan), ATG, and total body irradiation (TBI) conditioning followed by post-transplant methotrexate. The purpose of such conditioning prior to an allogeneic stem cell transplant is to suppress the recipient’s (patient’s) immune system to prevent graft rejection (i.e., facilitate engraftment) (Table 7.2). Ryan: I prepared for transplant by trying to eat healthy and get my life situated. The doctors and staff were very good at explaining everything…they made me aware of what could happen. I did not realize how many ways you can get graft versus host disease (GVHD). I thought it was just a skin and stomach reaction. I was probably told at some point of all the possible side effects, but when you are getting that much information in a relatively short period of time, you start to not even listen to what you are being told. My worst fear was that the transplant was not going to work but I kept that to myself. Ryan: I really didn’t feel like getting out of bed during the transplant because I was so sick. I had a few nurses who would strongly encourage me to do stuff. If the nurses didn’t push me, I wouldn’t even get out of bed. I couldn’t go outside because of the risk of infection … I felt locked up. I spent the day playing on my computer or watching TV. I wished I used some of the services offered. It would have been nice to have someone to talk to. I think when you are going through something like this it is hard to comprehend how to ask for Table 7.2  Allogeneic stem cell transplant, Cy/ATG/TBI conditioning regimen allogeneic HSCT Day −5 Line placed Admit ATG test dose— intradermal (no pre-meds) EKG 4 hours of IVF prior to Cytoxan Pre-meds Mesna pre Cytoxan & Mesna again starting with Cytoxan @1400 VOD prophylaxis begins

Day −4 Mesna @0200 ATG pre-meds/ mid-meds 6– 10 hour infusion Equine ATG Monitor closely for hyper-­ sensitivity reaction EKG Mesna @1400 Cytoxan @1400

Day −3 Mesna @0200 ATG pre-meds/ mid-meds 6– 10 hour infusion Equine ATG Monitor closely for hyper-­ sensitivity reaction EKG Mesna @1400 Cytoxan @1400

Day −2 Mesna @0200 ATG pre-meds/ mid-meds 6–10 hour infusion Equine ATG Monitor closely for hyper-­ sensitivity reaction EKG Mesna @1400 Cytoxan @1400

Day −1 Mesna @0200 TBI Cyclosporine IV begins

Day 0 Early review of the stem cell infusion checklist 4 hours of IV hydration prior to stem cell infusion Pre-meds Administer stem cells

Day +1 Methotrexate daily (+1, +3, +6, +11)

Conditioning: Cyclophosphamide/equine anti-thymocyte globulin/TBI (Cy/ATG/TBI) Disease: Aplastic anemia Filgrastim starts Day +7

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Table 7.3  Cancer supportive services  • Complementary care services such as visual art, literary arts, and music can be therapeutic and contribute to a person’s sense of well-being. One-on-one sessions may include journaling and creative writing, art therapy, music, reiki, and massage.  • Spiritual concerns are a natural part of an experience of critical injury or illness. Chaplaincy provides personal support, crisis intervention, spiritual care and guidance, short-term counseling, and liaison with local religious communities.  • The inpatient transplant nursing and medical team overseeing the daily care of each patient is highly committed to providing encouragement and compassionate support through the transplant process, but some patients do not utilize additional supportive services despite encouragement from the staff. help or where to go. It would be helpful if you have an idea of who to ask … when you’re sitting in a hospital bed sick the last thing you want to do is search for resources (Table 7.3).

Ryan: I was really excited to go home … I felt pretty good about it because I felt like the doctors thought I was doing well enough to be discharged … The only thing I was worried about was if I was going to have much help at home.

However, when Ryan got home, his feelings of isolation set in. Ryan: Every day was a challenge to even do the simplest things such as having the energy to take medications or to even want to turn on the TV. One of the hardest things was not having someone to talk to and feeling like I was going through this alone. My brother and fellow firefighters were helpful but there was a lot of time when I felt very much alone.

The inability to stay on track with his many medications led to recurrent bouts of GVHD and hospitalizations. He had very few visitors and so developed close relationships with the nursing and medical staff. He became family. On his good days, he was a fun-loving young adult who loved to joke and tell stories. On his bad days, he had a difficult time engaging in conversation due to his pain and inability to eat or drink, secondary to severe GVHD of his mouth and skin. The nursing staff brought him pints of Ben and Jerry’s ice cream since that was sometimes the only thing he could eat. Ryan: I was six months post transplant when the Fire Department paid all my bills, every month including my truck payment, cellphone, everything … if I really needed something I knew they were always there to help. When I broke my hip they all came and built a wheelchair ramp at my house. They would visit me in groups at the hospital … four or five guys at least once a week … they told me that if I needed anything to just ask … but it was hard for me to ask, so I just didn’t.

Ryan became good friends with Vivian, one of the nurses who cared for Ryan prior to transplant. He would come to the inpatient unit for transfusion support on the weekends. He was a big, burly, larger than life 19 year old. His main goal was to beat his disease and get back to firefighting. He entertained the staff with his jokes and funny stories and shared more intimate details of his upbringing with a few selected staff members, including Vivian.

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Extracorporeal photopheresis (ECP) is a standard treatment for GVHD that hasn’t responded to steroid therapy. During ECP, the patient’s blood is collected and treated in an apheresis machine, specifically the donor T cells causing GVHD symptoms, which are removed from the blood and inactivated via a photosensitizing source, then circulated back to the body. This really is a type of “targeted” (Star Wars-like) therapy. Some researchers have found changes in the blood after ECP that decreases swelling and inflammation. ECP carries a lower risk of infection than other GVHD treatments, like steroids or other medicines that suppress the immune system. Ryan: It has been a long and hard road since I was diagnosed. For the first few years after transplant I did not have a lot of support. Two years after my transplant, while I was receiving my twice weekly ECP treatment, Vivian came to visit me. She recognized immediately that I was in need of assistance at home. She insisted on helping with transportation to appointments, organized my medications, and checked in to make sure I was keeping up with everything. Over time, we developed a special friendship and started dating.

7.1 Nurse Vivian Comments on This Friendship Ryan has had a lack of family support all through his transplant. Even in his childhood, due to his parents’ challenges with mental illness, Ryan did not have a mother or a father in his daily life. This carried over into his medical care. He was often alone at home or in the hospital; his primary support were his nurses and his medical team. Over the years, his aunts and cousins stepped up to help and have been there for Ryan, visiting him during his many post transplant hospitalizations, sending cards and checking on him frequently. His friends have fallen off the face of the earth. Sometimes people, particularly younger people, don’t understand how to support someone who is sick and struggling. I am a highly organized, caring person. But, I’ve dealt with anxiety my whole life. So, you can only imagine how living through Ryan’s transplant and caring for someone who is so susceptible to so many potential problems can only intensify this anxiety. In a way it’s made me a stronger person because we have to deal with so much on a day to day basis … But, I’m always wondering when the next thing is going to happen and it’s not an if it’s a when. I’ve learned different coping mechanisms in terms of taking care of myself to be able to help Ryan as best as I can.

Ryan had a strong desire to meet his stem cell donor. Many stem cell recipients hope to connect with their donor after transplant, but there are privacy rules that limit when and how they can connect. Depending on what countries in which the recipient and donor reside, they may never be able to connect. These rules sometimes feel frustrating, but they are in place to protect the recipient and donor. Some recipients and donors don’t want to connect after transplant. There is no right or wrong choice, and both donor and recipient must agree to meet in order for this to occur. Three years after his stem cell transplant, while Ryan was receiving ECP treatments for GVHD, his BMT nurse coordinator brought him a packet from the National Marrow Donor Program (NMDP) with the contact information of his donor. The NMDP/Be the Match program has facilitated more than 92,000 stem cell transplants, and nearly 6200 transplants a year to give patients hope for a future.

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They are the recognized leader in unrelated marrow transplantation. Be the Match continues to develop services and interactive technologies used by transplant experts around the world to reach more patients. A soccer team in Germany had previously registered with the Delete Blood Cancer (DKMS) Bone Marrow registry hoping to provide a stem cell match for a teammate’s mother. DKMS is an international nonprofit organization dedicated to the fight against blood cancers and blood disorders. One of those athletes, William, was not a match for his friend’s mother—but he was a match for Ryan, who lived thousands of miles away in the United States. William is exactly 1 year and 7 days younger than Ryan. Because of William’s “gift of life,” Ryan received a successful stem cell transplant. William was a senior in high school when he was notified that he might be a donor for Ryan. He was filled with mixed feelings of uncertainty, excitement, and hope. When they connected on Facebook for the first time, William was nervous. The first thing he did was scroll down through the profile and look at all the information and posts, but the weird thing was that he didn’t have the feeling that this was a complete stranger, but rather a family member. Over the next two years, the two young men developed a friendship through social media and email. A lifelong brotherhood developed. Ryan: Four years after my transplant, I proposed to Vivian; it was a beautiful sunny day on the beach in Maine. Meeting Vivian changed my life; I do not believe I would be here today if it wasn’t for her love and kindness. After Vivian accepted my proposal the first person I announced the news to was my brother, Thomas; the second person was my donor brother William. I invited William to the wedding and he flew to the US from Germany with a friend. William and I met for the first time face to face at a bus stop in my hometown. We were surrounded by a cheering crowd - Vivian, my family, fire and police department friends, and my BMT Team. The next day, Valentine’s Day, my BMT Nurse Coordinator and the transplant team put together a reception welcoming William, discussing the importance of bone marrow donors and thanking him for saving my life.

A friend of William joined him for the trip to the United States. The friends talked a lot on their journey to the states. William was nervous and excited at the same time. Two questions kept coming to his mind: (1) How would the meeting with Ryan go? (2) What would William share with Ryan? When the friends finally reached the bus station, all William’s anxiety disappeared—it was a moment of pure joy and happiness. Ryan: That weekend, our families and friends gathered in a small country chapel on a cold winter day to see my beautiful bride, Vivian, in a stunning white gem speckled gown walk down the aisle with her father as I stood at the front of the chapel in a sharp tuxedo with my brother and fellow firefighters. Instead of a limousine ride to the reception, we were driven in a fire truck! Our guests were mostly nurses, medical staff, and firemen who danced the night away. It was a magical day. Our celebration was short-lived. The morning after our wedding I was confused; I did not know what day it was, forgot I got married, and my speech was slurred. Vivian took me

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straight to the emergency room. I was admitted and had to have a brain biopsy to confirm that I had GVHD of my brain. I underwent months of chemotherapy and ECP. As Vivian has also shared: The day after our wedding, He was diagnosed with GVHD of the brain requiring him to go on oral Cytoxan and receive months of ECP. The ECP commitment was a twice a week outpatient procedure. We really didn’t have much of a home life - the hospital was our life. Ryan has had so many complications from his transplant that for a number of years we were inpatient for weeks to months. When we were finally home we had up to 3 outpatient appointments with orthopedics, neurology-oncology, and hematology. He developed avascular necrosis (AVN) caused by the steroids required to minimize graft versus host disease. He had both shoulders and his hip replaced. He had multiple infections requiring antibiotic therapy. And Ryan recalled: I’ve been hospitalized many times post transplant. Five months after the transplant, I went to stand up out of the recliner and I hit the floor face first and could not move my limbs. My mom called 911 and I was transported to the hospital. I had tacrolimus (Pro-graf) toxicity. I was hospitalized for two weeks. It was slow getting my reflexes back. I developed avascular necrosis due to long term steroid use. I’ve had hip and shoulder replacement. My dog scratched me and I developed an infection. We had to give him away. Now I have two declawed cats. I’ve had GVHD of my brain, eyes, mouth and my skin. Never the gut. The brain was the most difficult … I’m still on medication for it … it caused me to lose consciousness … it was diagnosed by a brain biopsy … I have chronic GVHD of the mouth and receive treatment for that.

Although Ryan continues to face intermittent complications, he and Vivian are able to spend much less time at the hospital. Having a supportive caregiver monitoring potential side effects and complications, along with managing multiple medications and medication changes, has been instrumental in minimizing Ryan’s inpatient stays. Vivian: We are grateful for our time together away from the hospital. We are enjoying our summer going to the beach, heading to the lake down the street from our home, eating out, and visiting our families. We’re taking full advantage of our time together. We are hopeful that those long stretches of time where he is doing well are more frequent. There really is no way you can prepare someone for all the potential side effects of a bone marrow transplant. You don’t fully understand the issues until you’ve developed these side effects and realize how it actually changes your life and your daily routines. As much as our medical team, nurses, and coordinators do their best to educate the patient, it’s very difficult to comprehend when you’re feeling so sick, that you have a serious illness, and you’re only thinking about surviving. Ryan has taught me to always look at the positive and keep moving forward. What’s important is to live your life the best you can and don’t let things get in your way of doing what you want to do. And Ryan has said: Before transplant, I always viewed myself as a strong and energetic person. I always tried to do whatever I needed to make the most money, have fun, and further my career in fire services. Now I am not nearly as strong, don’t have much energy, am no longer looking to have the most money or the most fun. I will never be able to have a career in fire services because of my constant need to prevent infections and my physical limitations. But, I am happy helping people in any way possible and love spending time with my wife and family. People who know me and what I’ve been through will always see me as a sick person and that I have the same limitations I had during my transplant. I do not see myself as being ill.

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And Vivian adds: Vivian: I see him as being ill all the time. I’m always anticipating, What’s going to happen next? When is it going to happen? How bad is it going to be this time? Is he going to be able to overcome it this time? It’s hard to live your life like this. It’s hard to make plans. We had concert tickets to see a country band we both enjoyed. I had said to Ryan, we probably shouldn’t buy tickets because we don’t know if we’re going to end up in the hospital again. He replied, I don’t want to live my life like that, I want to plan things. I don’t want to live my life worrying about those what ifs. I try to be more like him and take things one day at a time. Finally, Ryan described himself this way: I see myself as a survivor. Before AA, I was a young man who was focused on myself and my life. Now, when someone is suffering with a cancer diagnosis it really makes me want to give back and share my story, provide support, and give them some resources ... my experience really changed my outlook.

Ryan has given back in many ways over the years by participating in Be the Match donor drives, volunteering for numerous cancer-related fundraisers, and active membership in the adolescent young adult support group. Whenever he gets the call to volunteer, his answer is, “Sure; when, and what do I need to bring?” Despite all he has been through, he has not lost his sense of humor or his ability to stay positive and take each and every day one step at a time. He and William continue to stay in touch, remaining “brothers in arms.”

Sources Consulted Georges GE, Storb R. Hematopoietic stem cell transplantation for acquired aplastic anemia. Curr Opin Hematol. 2016;23(6):495–500. https://doi.org/10.1097/MOH.0000000000000281. National Marrow Donor Program. (2022). Aplastic anemia. Be the Match. https://www.uptodate. com/contents/aplastic-­anemia-­pathogenesis-­clinical-­manifestations-­and-­diagnosis

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Letting Go Carissa Morton

Watercolor What is your meaning of Hope? It’s a little spark that keeps people going. Since I read that cardinals mean hope, I called my painting Bright Red Hope. My wish is to share happiness with people who can see it.

C. Morton (*) Dartmouth Health, Dartmouth Cancer Center, St. Johnsbury, VT, USA e-mail: [email protected] © The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 J. Coffey et al. (eds.), Patients’ Lived Experiences During the Transplant and Cellular Therapy Journey, https://doi.org/10.1007/978-3-031-25602-8_8

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HOPE LIKE A BLUE SKY Deb Williams Hope, like a blue sky, After the dark storm, Fills my soul, With joy. Hope, like a decision made, After the long struggle, Fills my soul, With peace.

In 2005, when Jack was about 50  years old, he was diagnosed with rheumatoid arthritis (RA). He tried a few treatments before transitioning to methotrexate. The methotrexate has immunosuppressive effects and has the potential to lower blood counts, so Jack had his blood drawn intermittently to monitor. In April 2010, his blood count dropped enough that his rheumatologist was concerned and decided to decrease the dose of methotrexate. At the next blood work check, the blood counts were lower and the methotrexate was stopped. The blood counts were checked again after a few weeks—all three blood lines remained low (red blood cells, white blood cells, and platelets). Jack’s rheumatologist then referred him to a hematologist/oncologist. The hematologist requested a bone marrow biopsy in November 2010. The results showed myelodysplastic syndrome (MDS). MDS is a diagnosis that constitutes a blood disorder/cancer that originates in the bone marrow, where the blood cells are formed. MDS is characterized by low blood counts and abnormal cell growth, such that it frequently transforms into a more aggressive and urgent blood cancer: acute myeloid leukemia. Jack went to the first few appointments alone and never told his wife, Jill, anything about his low blood counts until that November. Jill: His Rheumatologist actually told him they didn’t like the looks of his blood counts; mind you he didn’t tell me all of this until November of 2010. Jack: The only emotional part about it (the diagnosis) was going home and telling my wife the first time. Not knowing how she would take it. She seemed to take it OK. I’m sure that she didn’t show me—she probably thought it was kind of like–offhanded. I tried to make it offhanded. That was the only real emotional part about it. Jack: We just kept coming back and coming back. Then there was one day that the doctor came in and sat down and he looked a little nervous. He comes in and he goes “well, how are you feeling today?” and I was feeling great and he says “well I’ve got to tell you this and I don’t know how you’re going to take it” I said, “OK tell me, let’s get it over with, let’s see what’s going on.” and he says “you have something called myelodysplastic syndrome” “okay what’s that?” and he says “it’s known as pre leukemia” and I say, “okay, what do we do to fix it?” well he says “we will have to go do a bone marrow transplant” which is fine and I say, “okay when do you want to start next week, two weeks from now?” and he says “let’s take a little time on this- we’ll just keep an eye on it; we don’t want to hurry it, we don’t know if it’s going to stay in a limbo type or if it’s going to advance.”

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The hematology team began the background work of evaluating Jack for the future stem cell transplant (SCT). They gathered information to contact his siblings for HLA (human leukocyte antigen)  testing and checked on insurance coverage. Unfortunately, none of his siblings were a 10/10 match, so the transplant nurse coordinators then reached out to the National Bone Marrow Registry—regrettably this also did not find a suitable full, 10/10 match. At that time, the medical center where his hematologist was located could only perform full 10/10 HLA matched allogeneic stem cell transplants. A referral was made to a larger cancer center about 3 hours away from Jack’s home to get a second opinion and to look into a cord blood transplant or a haploidentical stem cell transplant from a 5/10 sibling match. This second opinion agreed that the best current approach would be watching and waiting until Jack became symptomatic or his blood counts dropped to more critical levels to begin any chemotherapy treatments or move forward with a stem cell transplant. Jack: I had already gone through my brothers as far as whether they could be donors and they were not 100% matches and they couldn’t find an unrelated donor match.

The local hematology team continued the “watch and wait” strategy since Jack’s MDS was not causing any symptoms or side effects. They monitored blood work every month or two, with provider visits a few times a year. Jack was thankful to be able to have blood work drawn at his local community hospital in the next town versus driving an hour to the medical center. Even with all that was going on internally in his body he remained the same active and hardworking family man. Jack continued to work full time in his labor-intensive job building and assembling countertops. He also continued to bowl multiple times a week in his local league, played golf, and above all spent time with Jill, his step-children, and grandchildren. For almost 6 years Jack was in this limbo. However, in April 2016 his bloodwork showed progressive decreases. He was officially neutropenic (low white blood cell count—specifically a low neutrophil count). White blood cells aid in infection fighting, and when they are too low, it increases a person’s risk of developing a serious infection. A repeat bone marrow biopsy was performed, which showed an increase in the abnormal cancer cells. Jack started Neulasta injections to help increase his neutrophil count and decrease the risk of infection (Tomblyn et al. 2009). At this point, his hematology team started talking about and moving down the path to allogeneic stem cell transplant (SCT). The searches through the national bone marrow registry still resulted in no available unrelated matches. The stem cell transplant world had advanced in the previous 5 years and had better protocols that decreased the risks of developing graft versus host disease (GVHD) in haploidentical SCT. To Jack’s surprise, his local medical center was now offering haploidentical SCT. One of his brothers, Nick, who was previously not thought to be able to donate was now medically cleared to be a stem cell donor. Things were starting to fall into place for a tentative admission for transplant in August 2016.

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Jack was well on his path to his SCT until he hit another road bump less than a month before the planned SCT date. He developed some “lumps and bumps” under the skin on his right arm and left leg. He was referred to dermatology, where they did a biopsy that showed subcutaneous panniculitis-like T-cell lymphoma (SPTCL). Another bone marrow biopsy and staging scan was done to evaluate for the lymphoma elsewhere in the body. The bone marrow biopsy was negative for lymphoma and showed less MDS than the prior study, and the scan showed disease only in the nodules under his skin. In October 2016, Jack started Targretin, an oral chemotherapy pill, in hopes of treating the lymphoma, which would allow him to proceed to his SCT. On the oral chemotherapy, the lumps started to shrink within weeks, and by the end of the year, the scans showed a complete response. Jack was finally headed to his haploidentical stem cell transplant with his brother, Nick, as his donor. Jack: I was happy because I had been sitting here coming back and forth once a month for 6 years and I’m not a person that wants to sit around waiting. Like I told Dr. Valley the first time, I’m a Vermont-er. Let’s get it cleaned up and get out of here.

Transplant Admission Jack: I was looking forward to my transplant because I’d been pushing to get it done and I wasn’t going anywhere—I mean we’ve got time, so I was looking forward to getting it done.

In January 2017, Jack was finally admitted for his SCT. He began his hospital stay on day −6 after having a tunneled central venous catheter placed in interventional radiology. His nurse oriented him to his room, daily routine, and hospital procedures and policies; vitals and admission height and weight were obtained. The following plan was also written on the whiteboard (see Table 8.1). During days −6 through −2, Jack received the chemotherapy outlined above without any issues. On day −1, Jack received total body irradiation. Jack also tolerated that pretty well. His nurse educated him about his stem cell infusion for the next day and made sure all his questions were answered. Meanwhile while Jack was busy at the hospital with the conditioning regimen, his wife Jill, who had been balancing visits with Jack, work, and home responsibilities, developed a cold and couldn’t visit for several days. Jill: After I left and I got home it really hit me, you know this is happening. I didn’t feel very good. I was coming down with a cold. What was going on?! I hadn’t had a cold in 2 years—well I think anxiety and stress sort of got to me at that point.

Day 0. Jack started his pre-hydration for 4 hours prior to the cell infusion. Jack’s brother, Nick, who was the stem cell donor, had his cells collected over the 2 days previously. The cells were processed and were ready to be infused. Jack tolerated the infusion well; he got his post-stem cell infusion IV hydration per protocol and rested for the remainder of the day.

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8  Letting Go Table 8.1  Haploidentical stem cell transplant, conditioned with Flu/Cy/TBI/Post Cy Day −6 Central line placed ECG Premeds Pre IV hydration Fludarabine Cyclophosphamide post IV hydration Day −1 Total body irradiation (TBI)

Day −5 Day −4 Day −3 Pre IV hydration Fludarabine Fludarabine Fludarabine 10 AM 10 AM 10 AM Cyclophosphamide 11 AM Post IV hydration

Day −2 Fludarabine 10 AM

Day 0 4 hours pre IV hydration Pre meds Administer fresh cells Post IV hydration

Day +4 ECG Cyclophosphamide 10 AM

Days 1 & 2 Day +3 Rest ECG 4 hours pre IV hydration continues until 24 hrs after day 4 cyclophosphamide Mesna infusion 48 hrs Cyclophosphamide 10 AM

Jack: During the stem cell infusion when the nurse slowed down the rate, you could see what looked like cells going through the tube—and that was really cool as far as I was concerned.

Day +3. After coasting through the conditioning chemotherapy, Jack received the post-transplant cyclophosphamide (50 mg/kg, a higher dose than the conditioning dose). This dose of cyclophosphamide was given on Days 3 and 4 after stem cell infusion per protocol to decrease the risk of developing GVHD. This development and change to the haploidentical SCT protocol greatly improved outcomes. An ECG was obtained each morning, and pre-IV hydration was started with normal saline and continued until 24 hours after the cyclophosphamide dose on Day 4. Mesna was also started and run over 48 hours as a bladder protectant to prevent hemorrhagic cystitis. After the cyclophosphamide infusion on Day +3, Jack became febrile at 38.4 degrees Celsius. Blood and urine cultures were sent, and a chest x-ray was obtained. Antibiotic coverage was switched to a broad-spectrum IV antibiotic, as directed per protocol. The chest x-ray showed no evidence of pneumonia, and Jack was encouraged to use his incentive spirometer. Day +4 brought more fevers and rigors. This was felt to be consistent with “cytokine storm”—a phenomena, which can be seen in haploidentical stem cell transplant. Jack was given meperidine for the rigors with good control. Jack’s weight increased due to the chemo and extra fluid; he required several doses of furosemide to help his body excrete the extra fluid. Cytokine release syndrome (CRS), sometimes referred to as “cytokine storm”: a whole-body inflammatory response driven by activated T cells and other immune effector cells. CRS can range from mild to severe. Symptoms include flu-like

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symptoms, fevers, body aches, headache, etc. Severe cases can also include hypotension, vascular leakage leading to edema and pulmonary edema, and multiorgan failure. In haploidentical stem cell transplants, mild cases of CRS are reported in approximately 75% of patients and severe CRS in about 12% of patients (Porter and Maloney 2022). The next several days were spent receiving electrolyte replacements, blood and platelet transfusions as needed, and trying to eat, drink, and walk. Jack hated the hospital food but enjoyed the shakes/smoothies the nurses made. He visited with friends and family when they came. Jack: My biggest fear during my hospitalization was my wife traveling from home to the hospital and back … The real spur in my back is the cooking and the food sucks.

Around Day +10, Jack developed significant back pain from the filgrastim (growth factor to stimulate engraftment) shots that started on Day +6. He also developed some vague chest pain and lightheadedness that was worked up by EKG but was negative. On Day +13, his central line was removed due to redness and tenderness around the exit site. On Day +15, Jack developed neuropathy, numbness, and tingling in the bottom of his feet. During the admission, Jack had become a bit weaker, and dealing with the pain and neuropathy, he used a front-wheeled walker for 2 days. Jack: I was walking with a walker which I hadn’t used before the transplant. She (the nurse) goes ‘what are you using that for?’ and I say ‘my feet my legs aren’t quite regular’ she said ‘well I’ll hold you up and you’ll walk with me’ and I said ‘okay’. So, I used the walker two days then started walking with her and then I just started walking again. The more I walked the better I felt.

Day +17—discharge day. Jack’s blood counts had recovered; he was eating and drinking adequate amounts and was able to walk and perform activities of daily living without significant assistance. Jack: I was excited to go home but I would miss my team … I knew who to call with issues/questions … Jill: I felt well educated about discharge since we had gone over that since admission, but I was scared; it’s like, oh brother here’s this whole page full of notes of everything to watch and look for and of course he had bottomed out at 162 pounds and this is a man that’s 210 pounds. It’s like okay how are we going to do this? What are we going to do? I mean, I had this lovely 5x7 magnet to call for any of these things, and I stuck it right on my refrigerator. Then I got home and went around doing my thing, and he sat in his chair. Every now and then it was like, you okay? You need anything to eat? Yes, you do! That’s when I think I was the most scared; afraid of what was going to happen if he started coughing? If he went to get up and he fell? If he started to have a fever? If he started to throw up and didn’t feel good? All I could think about in the back of my mind was; yes, I can call but it’s going to take me an hour and ten minutes to get down to the hospital—that was my biggest fear.

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8.1 Post-Stem Cell Transplant After discharge, Jack went home with Jill to continue the recovery process. His goal throughout the transplant process was to make it to a family vacation at a waterpark halfway across the country, in August—about 8 months after his PSCT. The nurses thought this was kind of a lofty goal; however, they never dismissed or dashed his hope. He used this as his motivation to keep working on eating, drinking, and getting stronger; although there were tough times and hurdles to overcome. Jack: I knew my wife was going to keep my butt in gear but I was pretty confident in where I stood and what I was doing, you know; I could move around. Before I left, I counted the steps around that little circle down there and so when I went home, I would know how far I had to walk. I couldn’t go outdoors but I knew I had to walk so I started counting steps— going upstairs and downstairs and all around my house. It’s just something that you got to pick up on yourself so that was fine … I thought—now it’s time to go home and recuperate. Once I got home it seemed to take longer for me to get back to where I wanted to be. Every morning I was getting pushed to do this pushed to do that. Jill: I told him, I am your nurse now and you’re going to listen to me, I actually told him that a couple of times I said look Lieutenant “nurse’s name” is no longer around, it’s Lt. Jill now, you’ve got to listen to me… In the beginning of March, I had to go back to work. Jack was home most of the time by himself. I would make sure to leave him notes—eat breakfast, have your snack, I will see you at noon time, etc. When I would come home at noon and ask him what he had to eat and he would tell me ‘Barely a protein bar’ and ‘what did you have to drink?’ ‘maybe a little bit of Gatorade’. I blew a gasket. It’s like look you have got to gain weight, you have got to put this weight back on, you have got to eat, you’ve got to get better. He would just say ‘well I just don’t feel like eating’ and I guess unless I’m in those shoes I don’t understand that. It got to the point where after a couple three weeks I was so on his case all the time about eating ‘you don’t have to have big meals but you have to have little things and you’ve got to have them all day long’. There was one day when I got home at noon he wasn’t there, so I figured he’d probably gone down to his father’s. When I got home at 5:00 pm he wasn’t there. I would tell him whenever you go somewhere you need to bring food, snacks, and a drink so you can have something to eat. Around 5:15 he called and said he was at the bowling alley. I said ‘oh what have you been doing all afternoon?’ ‘Well, I had to go help dad do something and then I had to stop down here to see so and so’. I asked what he had to eat from noon until now and he said ‘a candy bar in the machine’ and I said ‘well what have you had to drink?’ he said ‘a soda’. He said ‘I’ll be home in a little bit.’ I didn’t say bye, I hung up on him. He got home at 6:00. I had leftover shepherd’s pie and went upstairs because I didn’t want to talk to him. Instead of getting himself some supper he called his brother in Texas and asking how his girlfriend was doing who had been in the hospital. Well let me tell you what, I am more off the deep end. Finally, he got off the phone with him after 15 or 20 minutes and he decided to get himself some shepherd’s pie. I was in bed before 8:00 pm because I didn’t want to talk to him. Around 4:00  am he got out of bed to go to the bathroom and crash, bang, boom. I jumped out of bed ‘what’s the matter?’ ‘I’m alright, I’m alright, I know what the problem is I just got out of the bed too fast’. I lit into him, flipped the lights on, the whole nine yards

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In late May, early June, Jack developed a nagging cough. Since everything seemed to be on track, his hematologist said it could be allergies and suggested trying Claritin and keeping an eye on it. Jill: I want to say it wasn’t until just before we left to go on vacation the first week of August, we came down here (the hospital) the week before we left. Everybody finally decided that it was some form of graft versus host which they weren’t looking for that because that wasn’t part of the normal, you know. That’s when I said ‘look he’s been off the

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charts weird since the beginning of this so why shouldn’t this be any different with him’. He started going on all these other medications. It was okay for us to go on vacation but he couldn’t do any of the swimming or any of that stuff. Jack: The cough I didn’t expect. We were a little nervous about graft versus host. We didn’t know what that was going to be if anything. Whenever there was a situation that would come up, I would make a phone call and check in with my transplant team. We would come down; we would sit down and discuss the different things and ask questions and if I didn’t come up with it, Jill did. She was always there with me.

Jack was finally diagnosed with graft-versus-host disease (GVHD) of the lungs, causing him to cough. He was put on steroids to try to suppress his immune system, which helped a bit. He was able to go on vacation with his wife, children, and grandchildren. He met the goal he was striving for. Jack started back to work slowly, a couple days a week—not doing the exact job he did before but doing something. Jack: I think back to where I want to be. I feel stronger every day. I mean sometimes in the middle of the afternoon I’m a little bit beat … I’ll doze off on the truck for five or ten minutes then I’m ready to go again. I think it’s still that part of it is coming off of the steroids. I think I’m building back up a little bit of stamina. I’m looking forward to being able to go where the grandkids go, go back into the pools and stuff like that, being able to do my work around the house, being able to help my brothers-in-law and sister-in-law, go back to haying with my father-in-law, being able to do stuff that I want to do, being able to go back to work full time, and be able to help support the family. Everything has been limited and now that is easing up a little. Getting back to work two days a week has helped me mentally. My family have all been supportive. The biggest coping aspect for my wellbeing was getting back into my sports more. Golf and bowling.

Jack continued to deal with the lung GVHD. He was hospitalized a few different times for pneumonia/bronchitis. He has routine follow-up appointments and blood work checked. His immune system was still not “normal,” but he did not let any of this hold him back. He continued planning vacations/trips with his family, attending grandchildren’s sports games, and playing golf and bowling. Jack: I’ve never been a real future person … I’m day to day and being with family that’s the main thing. That hasn’t changed because of this process.

References Porter, D.  L., & Maloney, D.  G. (2022, March 3). Cytokine release syndrome (CRS). UpToDate. Retrieved November 12, 2022, from https://www.uptodate.com/contents/ cytokine-­release-­syndrome-­crs Tomblyn M, Chiller T, Einsele H, Gress R, Sepkowitz K, Storek J, Wingard JR, Young JA, Boeckh MJ, Center for International Blood and Marrow Research, National Marrow Donor program, European Blood and Marrow Transplant Group, American Society of Blood and Marrow Transplantation, Canadian Blood and Marrow Transplant Group, Infectious Diseases Society of America, Society for Healthcare Epidemiology of America, Association of Medical Microbiology and Infectious Disease Canada, & Centers for Disease Control and Prevention. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant. 2009;15(10):1143–238. https://doi.org/10.1016/j.bbmt.2009.06.019.

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Another Ode to August Lisa Wesinger

Puffted Titmouse ~Sharon Grader Photograph Even on the harshest Winter day there is such beauty to be found.

L. Wesinger (*) Transplant and Cellular Therapy, Dartmouth Health, Lebanon, NH, USA © The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 J. Coffey et al. (eds.), Patients’ Lived Experiences During the Transplant and Cellular Therapy Journey, https://doi.org/10.1007/978-3-031-25602-8_9

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THE NIGHT BEFORE TRANSPLANT Amelia Lincoln and James Patterson 'Twas the night before transplant and all through the room the chemo was finished, it would not resume. Tacrolimus was hung on the pole with great care. Amelia lay dozing, breathing HEPA filtered air. All the nurses had finished with vitals and meds and the patients lay sleeping in hospital beds. Then all of a sudden there arose such a din and to Amelia’s room the nurses rushed in. What did they see, but a sight very odd, their patient was dancing to tunes from her iPod. She just couldn’t sleep with transplant so near. She greeted the next day with no hint of fear. That day will begin with radiation downstairs that will cause her to lose all her soft little hairs. Then two cord blood units, one from Europe, one from here, will repopulate her marrow and the cancer will clear. The challenges will be many and should not be dismissed. They’ll be treated with meds that appear on this list: Ondansetron, Ativan, Fluconazole, Lisinopril, Zovirax, Ursodiol. When blood counts are low, transfusions she’ll need and infection precautions we all must heed. After some weeks her blood counts will rise and then she will shout with tears in her eyes. “I’m coming home Violet, don’t worry, don’t fret! I’ll soon be in Vermont with my fuzzy white pet, and all of the people who gave love and support, whose close faithful friendship cancer can't thwart." And then when the dancing had faded away Amelia lay down to rest for her big day. So think of her, friends as she gets radiation This trip to Boston is no vacation. She’ll be thinking of you as she gets her new cells. She’ll be thinking of you and wishing you well. So that when this is over and when this is done, We will all be together for years to come. Victoria: I do my best to relish every bit of August. Some years ago I spent its entirety ten floors up in a city hospital. I was unable to see green grass or to see my husband’s face without a mask. Unable to breathe fresh air, unable to eat fresh fruits or vegetables, unable to do so much. I was able to breathe, though, and I was able to hope and to dream for a future. I was able to put one foot in front of the other, at least some of the time, and I was able to endure.

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So, now when the eighth month of the year rolls around, I breathe the fresh air especially deeply. I listen to the song of the crickets, the soundtrack to August in Vermont, like it is a symphony. I eat fresh berries and produce from my garden, giving the cucumbers only a cursory wipe on my t-shirt before savoring them as I pull weeds, thrusting a bare hand in the rich soil while I munch. I mow the lawn and I pet the animals without washing my hands. I let the cat nuzzle my face and I walk with the dog feeling so grateful I am not attached to an IV pole. This month I’ll swim and I’ll eat soft-serve and I’ll drink beer which were among so many things I was forbidden to do for ages. I am still able to hope and to dream for the future, and some days it seems I am only able to put one foot in front of the other. Some days I still must endure and endeavor to persevere, but mostly I try to relish and to savor and to breathe in the month of August.

Victoria and William live in a rural area of Northern New England. This is where Victoria grew up, while her husband, William, is from the Midwest. They are supported by family, friends, and a close-knit community. Victoria served as a diesel mechanic in the Coast Guard and has always speculated about the impact of working with the fuel, solvents, and other chemicals that were part of her job and her diagnosis with acute myeloid leukemia (AML). At the time of diagnosis, she was a middle school teacher and William a photographer for a local newspaper. They had just purchased their very first home and were eagerly planning to start a family. In the Spring of that year, Victoria developed a terrible, painful rash that covered her whole body. She could not even tolerate the touch of a light bed sheet on her skin. She saw her primary care doctor and a dermatologist. They had no explanation for the rash and were unable to make a diagnosis. In the fall of that year, Victoria was starting her third year of teaching, and as the semester went on, she began taking more and more sick time due to unbearable fatigue. In December, she began having episodes of unusually inconsistent menstrual bleeding with alarming volumes of blood. By this time, she was unable to go to work or even write plans for her substitute teachers. She spent most of her days curled up in a blanket by the woodstove. Victoria’s new primary care doctor saw her a couple of times and prescribed an iron supplement. In the last few days of December, her doctor decided to do a blood test, and on December 31st when the results came in, the doctor called and told her to go straight to the hospital and get admitted to the Hematology/ Oncology unit. It was a Thursday night right before the long New Year’s holiday weekend, and they encountered staff members who seemed to be filling in on an unfamiliar unit. Several days later after blood tests and biopsy results returned, Victoria was diagnosed with AML. Victoria: I had recently turned 33 when I was diagnosed with AML. We had been married two years, just bought a house and were ready to start a family. Since my diagnosis, I’ve been part of four clinical trials and have had two stem cell transplants, one using my own stem cells at a large academic teaching hospital in Northern New England, and a cord blood transplant at a comprehensive cancer center in Boston. Life as we knew it pretty much ended, I had been progressively feeling ill and losing energy. By the time the doctor realized there was an issue I was very sick and was immediately admitted to the inpatient oncology unit where I stayed for over a month. William: As a result of the intensive chemotherapy, Victoria went into early menopause and is unable to have children. This was addressed on the day of her diagnosis, and it was determined that there was no time to harvest her eggs. I’m not sure anything could have been done differently since it was imperative to start her treatment immediately.

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In the first week of January, Victoria began induction chemotherapy for AML (Table 9.1). Victoria: We faced the day to day life in the hospital with total uncertainty and with a singular focus of survival. We never knew what side effect or complication was coming. I looked forward to showering and drinking coffee if I could. Everything was work: eating, staying awake, getting up to go to the bathroom. I looked forward to visitors and was grateful to my husband for keeping me supplied with clean pajamas.

Victoria experienced complications during induction chemotherapy, including retinal hemorrhage and a transient drop in cardiac function. She was closely followed by Ophthalmology and the Cardiology teams. These both resolved over time. William: During her induction, Victoria went into heart failure and was moved to the Hematology Special Care Unit (HSCU) where she improved. At the end of her induction she was in remission. Consolidation went well.

Victoria was in complete remission after induction therapy, meaning that there was no evidence of disease on her bone marrow biopsy. Review of her prognostic factors indicated that she was NPM1 positive (considered favorable, though more so in older patients) and FLT3-ITD and D835 negative (also favorable, as these are adverse mutations). She did manifest a novel three base pair insertion in her FLT3 gene, of unknown significance. Based on these findings, as well as a large retrospective review (Gale et al. 2005) showing no advantage of allogeneic stem cell transplant for patients with FLT3 mutations, the decision was made to avoid the potential toxicity of allogeneic transplant, with FLT3 status deemed irrelevant. Instead, Victoria was enrolled in a CALGB (Cancer and Leukemia Group B) working group trial (#10503) utilizing autologous stem cell transplant after intensification therapy and peripheral blood stem cell collection. Because of her normal cytogenetics, she was treated under the “poor prognosis” arm of the study. In early March, she began one round of consolidation chemotherapy (Table 9.2). Victoria was experiencing overwhelming anxiety related to her statistical probabilities, as discussed with her primary hematologist, namely, the potential for a long-term remission versus relapse following a stem cell transplant. Her provider requested a Palliative Care consult to help her cope and plan for her future. Victoria stated that she had been worrying about the prognosis, and it was keeping her up at Table 9.1  7 + 3 induction chemotherapy 7 + 3 Induction Chemotherapy Daunorubicin 90 mg/m2 IV push over a minimum of 3 minutes, once daily on Days 1, 2, and 3 Cytarabine 100 mg/m2/day continuous IV on Days 1–7 Table 9.2  CALGB 10503 chemotherapy/biotherapy consolidation CALGB 10503 Chemotherapy/Biotherapy Consolidation Etoposide 10 mg/kg, IV daily, days 1–4 Cytarabine 2000 mg/m2, IV q12 hours, days 1–4

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Table 9.3  Autologous stem cell transplant conditioning regimen Etoposide 60 mg/kg/day (−3) × 1 Busulfan 0.8 mg/kg/day (−7 through −4) × 16 doses

night. Since the Palliative Care consultation, she had had time to think and put things into perspective. She no longer felt as intensely concerned as she initially had. However, she wanted to do the right things; not putting her head in the sand, acting in denial or perseverating on the possibility of disease recurrence. Victoria decided she would utilize the many complementary services offered to patients (e.g., reiki, massage, creative writing, art and music). Victoria: For a long time I was very ill and saw myself as such. I felt physically ill for many months at a time, and my future was uncertain. It was necessary to push myself in so many ways and at the same time be cautious and not overdo it. William: I feared that Victoria would die, or suffer alone, and that the treatments would destroy her quality of life.

By the end of March, Victoria’s stem cells were successfully collected. Her heart failure had completely resolved, and her retinal hemorrhages were on the mend. Victoria was ready to be admitted for an autologous stem cell transplant conditioned with high-dose etoposide and busulfan (Table 9.3). *Note: This protocol is no longer used to treat AML. Overall, Victoria’s admission for transplant went well. She developed pancytopenia, neutropenic fever, and mucositis, but her mouth pain was well controlled with a patient controlled analgesia (PCA) pump. She stayed positive and motivated and was greatly supported by William, their friends, and family. William: When Victoria felt well enough, we walked laps around the unit. We read books together and watched movies. Victoria has a supportive group of friends and family, so she had an abundance of visitors when she felt well enough to see people. They would relieve me and stay with her so I could go home, rest and do laundry. We wrote songs and poems together.

As part of the CALGB 10503 protocol, Victoria received 8 cycles of decitabine. A bone marrow biopsy two years after her diagnosis (1 year after her stem cell transplant) showed no evidence of disease. However, in early spring of the following year, she began noticing small bruises and petechiae over her chest and extremities. She verbalized that her “lips were buzzing,” somewhat reminiscent of a low calcium level. She was experiencing new fatigue and worsening bruising. A CBC showed pancytopenia and a blast count of 76%, suggestive of relapsed AML.  Induction chemotherapy with high-dose cytarabine (HiDAC) was initiated because a non-­anthracycline-­containing regimen carries the lowest risk of having recurrent cardiac toxicity. Her hospital course was complicated by disseminated intravascular coagulation (DIC) with significant ecchymosis, vaginal bleeding, and mild oozing per rectum with diarrhea. She also developed typhlitis, an inflammation of the cecum, with splenic flexure thickening in the setting of high stool output. By

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early May, Victoria was discharged to home after a successful re-induction with HiDAC. William: Almost two years after her autologous stem cell transplant, during one of her regular checkups, her primary hematologist called her as she drove home and told her to return to the hospital. Her blood tests showed signs of a relapse. Victoria underwent induction and consolidation chemotherapy. Family members were tested, but none were a good match. We did a donor drive, but were already moving toward a cord blood transplant in Boston. Again, Victoria worked very hard to stay active.

Victoria and her provider discussed the next steps. At that point, the only potentially curative options were cord blood, mismatched donor, or haploidentical donor transplants. They discussed each, including the rationale for their respective approaches and the relative advantages and disadvantages of each option. They reviewed associated preparative regimens, risk of infection and acute and chronic graft versus host disease (GVHD), and what Victoria’s life might be like after an allogeneic stem cell transplant. They discussed the research and evolving nature of these approaches and that, at that point in time, the treating institution did not perform any of the outlined procedures. However, Boston, New York City, and Seattle were all feasible alternatives for any of these three options, with active protocols, research, and extensive experience. After this discussion, Victoria and William decided they would prefer to start with a consultation in Boston. Victoria: My worst fear during the admission was death. Prolonged suffering and death. Not being able to fully live my life, and causing my loved one grief. When we were weighing options for my second transplant, I was very afraid of having a transplant with a higher likelihood of GVHD. I was afraid to have a painful or life limiting condition, and I was worried about what my quality of life would be. I’m incredibly lucky to be here and to not have chronic issues. I’d say we were as prepared for the admission to transplant as anyone can be for something like that. There are so many variables and unknowns.

Victoria was admitted to a comprehensive cancer center in Boston that summer for a dual cord blood hematopoietic stem cell transplant for FLT3+ AML conditioned with busulfan, fludarabine, and total body irradiation (TBI). Her Day +30 chimerism was 95% donor! William: That summer, she had her transplant with two cord blood units. Shortly after being released from the hospital in early September, Victoria developed cord blood colitis. She endured a series of infections, including Clostridium difficile and sepsis that sent her to the ICU. It was speculated that the infection came from her central venous access device that was inserted the previous winter. She had been receiving total parental nutritional (TPN) support for months through her central line. Victoria: When I was getting ready for the second transplant I likened it to heading off to war; it was going to be hell and there was a good chance that I wouldn’t be coming back. I believe the pre-transplant education was pretty thorough. Doctors and nurses were patient, answered questions, and gave us resources. I’ve come to find out that not everyone knows or wants to know what’s going on. We absolutely felt like an active and informed participant in my care. We wanted to understand the process and rationale, and I know now that not everyone does.

9  Another Ode to August During the transplant I had pages of side effects. Sometimes it seemed like I was experiencing every possible one listed (including nausea, vomiting, diarrhea, loss of appetite, rashes, heart failure, skin issues, mouth sores, retinal bleeds from vomiting, etc.). Yes, they were mostly well managed, with a few exceptions. As William observed: We were more prepared for the second transplant, having gone through it once already, but after several months of chemotherapy for her initial diagnosis, we were very familiar with the hospital and staff and had learned a lot about AML. Nothing could have prepared us for the initial diagnosis. I think both of us would have liked more information about research studies, but Victoria found a lot of her own information and was persistent with questions about studies relating to her specific condition. At first there was more information than we could process. Trying to interpret and convey the information to family members by email helped. We used the educational pamphlets available in the hematology/oncology unit and asked lots of questions. Victoria was better at asking questions and forming relationships with the doctors and nursing staff, but it was sometimes important for me to be there to help her remember things, interpret her thoughts, and take notes. I tried to stay away from searching the internet for information. I think there is a fine line between too little information and too much information. We seem to have found a balance. Our day-to-day life was grueling. I spent most nights by her side. I worked as much as possible and was away from home the majority of the time. We learned the basics of playing the ukulele with a music therapist. I took as many notes and photographs as possible. Victoria experienced nausea and pain during her transplant, especially when eating. She also suffered from vomiting, vision changes, neuropathy, difficulty focusing and thinking, fluid retention, heart trouble, cracked and peeling skin, hair loss, and anxiety. I think they were fairly well managed, except when they weren’t. There were a few times that Victoria was retaining a lot of fluid and it caused her some serious discomfort, and I think fluid building up around her heart and lungs put her in the most dire situation of her whole hospitalization. I think that a combination of Victoria’s independence and the fact that she was sometimes perceived as young, “healthy,” and intelligent may have caused situations in which staff focused on other patients more directly in need as Victoria’s symptoms worsened. On the whole, Victoria received very good care and attention. She had a hard time being confined to the indoors for such long periods. She loves to be outside, and I worried that she wouldn’t be able to enjoy the outdoors due to all the restrictions placed on her. She’s also vegetarian and was unable to eat a lot of her favorite foods due to restrictions on her diet. I hoped that she would be able to return to eating wholesome fresh food and actually enjoy it. Victoria acknowledged mixed feelings: When it was time to be discharged, it was scary. It was scary for my husband as he felt responsible for my care and for the environment I was in. Going from a place where you had a nurse call button a push away and you had your temperature taken every four hours to home was stressful. Oh, and elated to be going home. Her husband described the positive outcomes after her treatment: When it was time to be discharged from the hospital after transplant, I was nervous. It can be easy to get comfortable with an entire cast of characters attending to a patient’s needs and answering any questions, then suddenly you have to make all those decisions on your own. One of the hardest decisions to make after being discharged is when a symptom or concern rises to the level of calling the hospital. Going from such a controlled environment to your own home, where it seems any small amount of dirt or a hug from a caring person who has the sniffles could kill you, can be really unnerving. Victoria and I were so used to the hospital, we live close enough, and Victoria formed such good relationships with her doctors and nurses that I think it went very smoothly. When Victoria no longer had a central line, however, she got pretty tired of getting stuck

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L. Wesinger with needles on each visit. After her second transplant in Boston, it was more difficult, because for a while we had to make that long trip so frequently. The following year, Victoria got a compression fracture in one of her vertebrae after falling from her bike. That summer, Victoria was diagnosed with Lyme Disease and was treated with antibiotics. Victoria had a fecal transplant in the winter due to ongoing colitis. Victoria did not return to teaching full time, but did some substitute teaching and worked as an office manager for the local chamber of commerce. Victoria is now in her third year working as a student assistance professional at three local schools and has just begun a master’s program in clinical mental health counseling. She has also been a volunteer at the Outpatient Cancer Clinic and is a founder of the hospital’s young adult cancer support group. She is now a facilitator of that group. However, their lives have changed in unexpected ways: I am just tired now. Unfortunately, during the whole ordeal, I had the most clear and unrelenting purpose. Now that she’s been well for so long I’m either not sure what to do with myself, or if what I’m doing worthwhile. But that’s improving. I’m not sure how other people see me now. Some have an ongoing sympathy even five years after Victoria’s second transplant. This whole ordeal seems to have excluded us from a whole social group. For Victoria, the benefits of treatment have far outweighed its costs: Life is certainly precious. I think I view myself as tenacious and capable in ways I hadn’t before. The outpouring of support we received made me think about myself differently. Not exactly like going to your own funeral but a glimpse of seeing what you mean to people. People use clichés like inspiring and a miracle when they see me. It used to be that everyone I knew, knew ‘my cancer story’, but I have people in my life who don’t know it, which feels good. I’ve taken a few years to disclose it to my coworkers because I haven’t wanted them to see me just through that lens. It feels good to have a little ownership of my story and experience instead of having people see me as a cancer patient or leukemia survivor.

Reference Gale RE, et al. No evidence that FLT3 status should be considered as an indicator for transplantation in acute myeloid leukemia (AML): an analysis of 1135 patients, excluding acute promyelocytic leukemia, from the UK MRC AML10 and 12 trials. Blood. 2005;106(10):3658–65. https://doi.org/10.1182/blood-­2005-­03-­1323.

10

Doctor’s Orders Ashley Prokopik

Photograph Prayer is a powerful tool and as a volunteer Bible educator I believe this and I teach this to others. So, my faith in God’s ability and His desire to give all of us whatever help we individually need never waivered. After my cancer diagnosis, I got down to the task of dealing with this health issue and getting things ready for an artist’s gallery where I sold my items. One of these was a favorite photograph of mine. It is a winding path through birch trees in the autumn; a beautiful pathway full of hope and wonder. What lovely sight would meet my eyes if I were able to walk through that photo and turn the curve at the end of the path? But now it looked different. Was it darker, kind of scary as if part of a fairy tale like Hansel and Gretel? Was there a wicked old witch waiting around the bend, or even death? Snap out of it, I said. Death is an enemy and with the help of Jehovah (that

A. Prokopik (*) Nashua Dartmouth Cancer Center, Dartmouth Health, Nashua, NH, USA e-mail: [email protected] © The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 J. Coffey et al. (eds.), Patients’ Lived Experiences During the Transplant and Cellular Therapy Journey, https://doi.org/10.1007/978-3-031-25602-8_10

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is God’s name) who wants us all to live forever, a healthy forever, you can fight it. So, with lots more prayers, and more faith in God’s ability and desire to help us, as mentioned before, I know that the path in my photo has a bright and shiny happy ending. Even if the cancer gets me I know it will be like sleeping for a little while and then I will be awakened by Jesus, God’s Son (Matthew 28:18), to a paradise earth where all of my friends and loved ones will be watching to come and meet me, even those who have been taken by death but whom have also been resurrected. We will be able to walk down the path between the birch trees and see what wonderful things are around the curve at the end of it.



WHEN I CLOSE MY EYES Tom Davis Mirror on the wall, can it be That old man’s face belongs to me Say it isn’t so, so I’ll know It’s just my eyes deceiving me When I close my eyes, I can see Once-upon-a-time staring back at me Always on the go, don’t say no Why can’t this go on endlessly Then one day something changed, rearranged The easy life I held so dear My body had been strong for so long With eyes closed I still see it clear Then I look to my lover’s face I see her smile, her grit, her grace And all the gifts she has to give And all the love that’s helped me live So hold your lover close, and believe In love you give and you receive Open up your eyes, see this day Let go the past and let it fly away Open your eyes Dr. West: “I quickly noticed increasing shortness of breath. Being a physician, we’re very good deniers. I thought I hadn’t been exercising much, and it was really minor shortness of breath.”

A primary care physician, Dr. West presented to his primary care provider with shortness of breath. An avid road biker on vacation, he had noticed that his exercising had become increasingly difficult. Tasks he was once able to complete now fatigued him, and his increasing dyspnea became concerning. With new onset edema, Dr. West cut his vacation short and came to his primary care physician with concerns about heart failure. However, after some lab work, a platelet count of 5000 mcL and a hemoglobin of 5 g/dL explained his fatigue and shortness of breath. A bone marrow biopsy was completed showing hypercellular marrow with extensive involvement (70–80%) by acute myeloid leukemia (AML). With the diagnosis and beginning of treatments, Dr. West’s life quickly changed.

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Dr. West: “So it changed my entire life. I was working full time as a physician and medical director. I had an active social and physical life. On Wednesdays, my friends and I would meet to ski until noon. It was a routine ritual that was a part of my life. And it was suddenly gone. All of it. Withdrawing from activities I identified with, both work and personally, was a big source of difficulty.”

Dr. West completed his “7 + 3” induction (Daunorubicin for 3 days and Cytarabine for 7 days), then 1 cycle of HiDAC (high dose Cytarabine) consolidation therapy to maintain remission before transplant, without complication. After his HiDAC treatment, he experienced a bacterial infection, and with successful treatment was discharged home to await transplant. Seventeen years prior to his AML diagnosis, Dr. West had undergone treatment in Boston for Hodgkin Lymphoma. This included radiation and a chemotherapy regimen called ABVD (Adriamycin; Bleomycin; Vinblastine; Dacarbazine). Such treatment replaced a long-standing regimen known as MOPP (Mechlorethamine; Oncovin; Procarbazine; Prednisone) chemotherapy in the mid-1970s, largely due to concerns over infertility risk as well as the potential for treatment-related AML from the former therapy. In the years that have followed, ABVD has proven to be both a highly effective and much safer treatment than MOPP in both respects, with the risk for secondary AML being notably reduced and approaching that of the normal population beyond 10 years out from ABVD therapy, albeit not absolutely zero (Brusamolino et al. 2012; Schonfeld et al. 2006). Dr. West was admitted for an ABO-matched, related allogeneic stem cell transplant with Fludarabine, Busulfan, and Rabbit ATG (anti-thymocyte globulin) conditioning. The fludarabine has an immunosuppressive effect that minimizes the risk for graft rejection. The busulfan has a cytoreductive benefit that helps to keep the AML in remission, awaiting a more durable graft vs. leukemia effect. ATG, along with methotrexate (MTX), is given for graft vs. host disease (GVHD) prophylaxis. Dr. West: “When you get a bone marrow transplant, there’s a piece of someone else in you. When I get my blood drawn, I see my sister’s blood now. We were estranged for many years due to a personal issue, but when she heard I needed a donor she jumped right in. She’s my only sibling and she was a 10/10 match. I have a part of her and our relationship turned around completely. The old stuff is just water under the bridge. We have a good relationship now.”

Being a physician, Dr. West was well educated about his care. He was attentive to all aspects of his medical care and asked frequent questions. He was an active and informed member of his care team. Dr. West: “The physicians were very willing to work with me on my concerns. They would alter therapy if reasonable. Sometimes I would insist an intern check with their attending first.”

Dr. West was given a phenytoin loading and maintenance dose due to the seizure risk related to busulfan. ATG left him with fatigue, diffuse body aches, and chills without fever, side effects that are expected with this agent. Anna, Dr. West’s caregiver and wife, would stay at the bedside as much as she could. Dr. West: “I was knocked out cold one day. My wife said to the nurse, ‘Is he going to be alright? I have plans with my mother tentatively. Should I stay here?’ The nurse said for her

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to go and that I would most likely just sleep. It was a good level of comfort to have, knowing people were there, as difficult as the process was to endure.”

An interesting point to Dr. West’s course was that his tacrolimus levels consistently remained sub-therapeutic. Clinical pharmacology recommended avoiding administration with other fat-soluble medications, such as vitamin D or ursodiol, along with administration well before breakfast and after dinner to avoid any interactions that might reduce absorption. Other complications included mucositis, oral thrush, and bone pain. Dr. West: “I couldn’t believe the bone pain. My sister had complained about it because she was my donor, but I didn’t realize how bad it was. I know some people get it and some people don’t, but mine was so bad they had to give me dilaudid.”

Granulocyte colony-stimulating factor (“G-CSF,” or “growth factor”) is given to bone marrow transplant donors to stimulate the mobilization of stem cells from marrow to blood that can then be collected from the blood by a process called stem cell apheresis. Stem cells can then be frozen to preserve until the transplant date. Growth factor is also given to transplant recipients to stimulate engraftment of the new marrow. Bone pain is an expected, though sometimes severe, side effect from growth factor administration. Dr. West’s stem cell reinfusion (day 0) went without complication. He experienced some minor flushing, coughing, and throat irritation, common with stem cell introduction. Many of these symptoms can be attributed to dimethyl sulfoxide (DMSO). DMSO stabilizes the stem cells during the freezing and thawing process during the storage period prior to stem cells being utilized. Dr. West: “If anyone tells you about the cells and they just tickle the back of the throat, they’re wrong; it’s absolutely horrible. I tried to hyperventilate because the DMSO exits through your lungs, and next thing I know a bunch of nurses are around saying I’m breathing too quickly. I said ‘No, I’m just doing an experiment!’ But aside from those things, it was relatively uneventful. I was discharged when my counts started to recover and I was very fatigued.”

Awaiting cell count recovery, Dr. West was prepared for discharge. With a heightened risk for infection, strict cleaning protocols for home and instruction on wearing masks outside the house was explained. Dr. West: “I view myself as vulnerable now. It’s constantly reinforced with your risk for infection. I had never before in my life felt vulnerable. It’s humbling. Masks are very separating. Kids would look at me in elevators; it was almost like a signal to strangers. It was very difficult.”

Recovery was an ongoing process, with a transition to outpatient care, including routine lab work, transfusions, and follow-up with the oncology team. Dr. West: “After my transplant, I was so fatigued. My hemoglobin was only 9 at times. We didn’t ask my friends for help, but they got together and made a schedule from November through April, until I was strong enough to make the 2-hour drive. It was a double benefit because I was so fatigued I wasn’t able to go out socially, and this afforded me time in the car to just socialize and interact.”

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Dr. West continued to recover and resume activities he enjoyed, such as snowshoeing and biking. Dr. West: “After the transplant itself, I got back to really good performance status. I got cocky; I thought this was a piece of cake.”

A rash developed following tacrolimus and budesonide taper, which was resolved by resuming budesonide and triamcinolone cream. However, completing a bike ride with his wife, Dr. West noticed he was falling behind more than normal. He had also developed gastrointestinal symptoms and assumed he had contracted the Norovirus. Dr. West: “I had an initial confusing interaction with phone management which delayed my diagnosis. I was admitted for a pretty traumatic course, I was putting out 2 liters of stool plus a day, my albumin was down to 1.7. I was in the hospital for 5 or 6 weeks. It tore the rug right out from under me.”

An infectious work-up of the stool was negative. An endoscopic assessment of the duodenum, stomach, and colon showed crypt apoptosis that was consistent with acute graft vs. host disease (aGVHD). Dr. West was admitted for gastrointestinal graft vs. host disease (GI aGVHD). He was also noted to manifest anasarca (generalized swelling) and lower extremity edema thought to be related to low oncotic pressure due to protein malnutrition. He utilized compression stockings for both upper and lower extremities in an attempt to reduce swelling. Methylprednisone 40 mg BID and IV fluids were started to treat the GI aGVHD. Dr. West continued with increased stool output. Dr. West: “I had the classic moon face from the steroids. Once I finally tapered off of them, my wife said ‘look, your face is getting much thinner.’ I also developed posterior cataracts that had to be surgically corrected, but for the first time since I was 12 years old I no longer needed glasses.”

He was placed on an increased dose of methylprednisolone, mycophenolate mofetil, TPN, budesonide, and a clear liquid diet. After bowel rest, Dr. West’s diet was slowly advanced, which was well tolerated. His TPN was changed to nightly. He continued with small amounts of diarrhea, which he reported was improving slowly over time. His methylprednisolone was changed to prednisone. Dr. West: “I have profound steroid myopathy, also known as muscle weakness. I used to have these biker legs, now I look like an anorexic 12-year-old.”

The mycophenolate mofetil dosing was increased due to continued diarrhea. Dr. West then noted decreased stool output, and a prednisone taper was begun. His anasarca improved with aggressive diuresis. He was discharged home with his wife from the hospital. Dr. West: “I believe you need a multidisciplinary GVHD team. It is the complication of allogeneic transplants, and the incidence is quite high. It makes sense to have a more ­organized approach and to anticipate the treatment, especially as older people are getting transplants with 30 or 40% unrelated donor matches.”

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In order to optimize control of his GVHD and facilitate tapering of steroids, Dr. West was started on extracorporeal photopheresis (ECP) while in the hospital, and this was continued as an outpatient, with him eventually completing 72 weekly sessions. ECP represents one of the few therapeutic modalities for steroid-refractory or steroid-dependent GVHD that is not inherently immunosuppressive. While the precise mechanism of action remains poorly understood, the general principle is the separation of mononuclear cells (including T-cells) via the apheresis process and then exposure to UV light, thereby causing cross-linking of DNA strands and ultimately apoptosis (programmed cell death). However, most of the effect does not result in the direct killing of allo-reactive T cells, but, rather, a downregulation of the donor immune response against host tissue (Nygaard et al. 2020). Thus, ECP can be a pivotal intervention to successfully manage GVHD for many patients, as it was for Dr. West. Ultimately, ECP was restarted in the setting of chronic GVHD (both lung and skin), and intermittent treatments that remain ongoing have managed to keep this in check. Even after the long and arduous road of a bone marrow transplant, Dr. West was not out of the woods yet. In March 2020, when the first draft of the SARS-CoV-2 virus was rapidly starting to make its way across the United States, Dr. West was in Florida. He and his wife drove north, visiting their friends and staying in hotels. They took every precaution, utilizing hand washing and avoiding people as best as they could. However, given his prior chemotherapy, transplant, and GVHD history, he was at a high risk for complications from COVID-19. After returning home to Vermont, Dr. West and his wife were feeling unwell. Though his wife recovered several days after developing symptoms, he was admitted to North Country Hospital due to a persistent fever and weakness, and he tested positive for COVID-19. He developed shortness of breath, requiring oxygen, and a chest X-ray showed an infiltrate. “Dr. Hill arranged for me to be transferred to DHMC right away,” Dr. West recalled, “because that very day was the start of the remdesivir trial.”

Remdesivir is an antiviral medication utilized to minimize symptom severity and expedite recovery from COVID-19 infection in hospitalized adult and pediatric patients. In an effort to impact the rapid spread of potentially fatal COVID-19 infections early on during the global pandemic, the FDA expedited access to this drug via the emergency-use-authorization (EUA) provision to enhance support to those with serious enough illness to warrant hospitalization. Ultimately, remdesivir has been shown to reduce mortality in patients treated within 7 days of symptom onset due to COVID-19 infection. In Dr. West’s case, he was an immunocompromised and highly susceptible individual to the most severe effects of this infection who was manifesting still early, yet progressive, symptoms requiring immediate hospitalization. The drug was in limited supply, though being delivered to our hospital at that moment, and getting him here to initiate timely therapy was paramount (Beigel et al. 2020; Karolyn et al. 2022).

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Dr. West came to Dartmouth Hitchcock to take part in the trial for this new drug. He had his signed consent in hand for the research trial for the antiviral medication, but he was too weak to show it to the research nurse through the window. He didn’t remember texting his wife “on six liters of oxygen. Not good” (Seidman 2020). Dr. West was intubated to make his work of breathing easier and provide critical oxygen to his essential organs. Fortunately, he was extubated after 5 days. Dr. West: “I think the very early intervention was instrumental in turning things around for me … If I hadn’t been close enough to an academic medical center with the option of the clinical trial, I would likely have remained at my community hospital and been treated with hydroxychloroquine, put on a ventilator, and that’s it. The timeline of getting to DHMC and getting on remdesivir created a window of opportunity for me that made a difference in my survival.”

In August 2020, Dr. West’s wife reported he was “even better than” his prior functioning status. He did not note any significant side effects from his challenging brush with COVID-19. Dr. West: “This experience has made me even more determined to be consistent about exercising and doing the things that help keep me healthy. I received exceptional care and I’m so fortunate. Now I’m just enjoying each day as it comes.”

Despite complications, Dr. West continues to lead a busy life, traveling, enjoying holidays with family, and continuing his healthcare journey. He spent most of the summer in Massachusetts after being cleared by his medical team, enjoying the activities he loves like boating and spending time on the beach. He picked up playing the guitar again and experimenting with photography. He also continued writing, hiking, and spending time with his wife and pets.

References Antiviral Drugs That Are Approved, Authorized, or Under Evaluation for the Treatment of COVID-19 [Review of Antiviral Drugs That Are Approved, Authorized, or Under Evaluation for the Treatment of COVID-19]. (2022, September 26). NIH.GOV; National Institute for Health. Beigel JH, et  al. Remdesivir for the treatment of Covid-19  - final report. N Engl J Med. 2020;383(19):1813. Brusamolino E, Gotti M, Fiaccadori V. The risk of therapy-related myelodysplasia/acute myeloid leukemia in Hodgkin lymphoma has substantially decreased in the ABVD era A-abolishing mechlorethamine and procarbazine and limiting volumes and doses of radiotherapy. In: Medical Journal of Hematology and Infectious Diseases, 4. Open Journal: System; 2012. Karolyn M, et al. Early administration of remdesivir may reduce mortality in hospitalized Covid-19 patients. Cent Eur J Med. 2022; https://doi.org/10.1007/s00508-­022-­02098-­9. Nygaard M, Wichert S, Toss F. Extracorporeal photopheresis for graft versus host disease: a literature review and treatment guidelines proposed by the Nordic ECP Quality Group. Eur J Haematol. 2020;104(5):361. Schonfeld SJ, et al. Acute myeloid leukemia following Hodgkin lymphoma: a population-based study of 35511 patients. J Natl Cancer Inst. 2006;98(3):215. Seidman, L. (2020, December 9). Saving lives, serving science: clinical research in our rural community [review of saving lives, serving science: clinical research in our rural community]. Giving in Action.

11

Am I Dreaming? Judi Gentes

Acrylic For a man who can’t sit still, always has to be moving and doing something…my woodworking hobbies had to be set aside. My brother, whose stem cells I received for my transplant, inspired me to start painting, even though I never painted anything except a house…70 paintings later.

J. Gentes (*) Oncology/Hematology, Dartmouth Health, Lebanon, NH, USA e-mail: [email protected] © The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 J. Coffey et al. (eds.), Patients’ Lived Experiences During the Transplant and Cellular Therapy Journey, https://doi.org/10.1007/978-3-031-25602-8_11

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PUT ON THE GLOVES AND FIGHT Judy Doherty Do I put on the gloves today? Can I do this one more day? Do I have the strength to fight? Can I face the uncertainty? Will I be alone in this fight? Will I have help? Yes! I will put on the gloves today! I can do this one more day! I will find the strength and will fight! I will face the uncertainty with hope! I am not alone in this fight! I have help all around me! I do not have to fight alone. “Am I dreaming I am ill and receiving a diagnosis of leukemia?”

It was Thanksgiving week when Mitchell, who had never called out of work in the past 3 years, began to have flu-like symptoms that caused him to stay home from work for a couple of days. Mitchell is a 40-year-old man who lived and worked in the small town of Peterborough, NH, with his girlfriend, Heather. Mitchell works as a project engineer designing aerospace lighting. The fever and chills were relentless, and all he could do was sleep and drink water. He felt “horrible.” After a few days of staying home and resting, Mitchell felt well enough to travel to Connecticut for Thanksgiving dinner at his sister Leah’s house. After an uneventful holiday weekend, Monday arrived, and Mitchell felt as though he could go back to work. As the day progressed, he began to get chills and a fever; he couldn’t get warm and began shaking at his desk. Mitchell’s boss sent him home after observing his symptoms and advised him to make an appointment with his doctor. Mitchell slept on and off throughout the night suffering with fevers, chills, and night sweats. It wasn’t until Tuesday afternoon that he went to the small local hospital emergency room in Peterborough, NH, where he lived. Lab tests were taken, and he was found to have a significantly elevated white blood and profoundly low platelets. Mitchell remembered: “The rather polite ER nurse or doctor said you either have a really bad infection or leukemia; we will figure out what to do.”

Left with more questions than answers, Mitchell was sent to Manchester, NH, hospital where more tests were obtained, until about midnight. Mitchell was admitted and continued with chills and fevers throughout the night. In the morning, the doctors came to his room and said they were 99% sure that he had a form of leukemia. Mitchell recalled the onset of his illness;

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“It was very quick ... just came out of the blue, I was never sick, I had not called out sick from work for three years.”

Facing this unexpected diagnosis, Mitchell was given a choice to treat his leukemia either at the cancer center in Boston, MA, or the cancer center in Lebanon, NH. He chose the cancer center in Lebanon, NH, because he also worked in that city; he felt it would be more convenient for him. Mitchell was transferred and admitted to the hospital that evening. He presented with continued fevers, night sweats, and weight loss. On December 1, a marrow biopsy confirmed the diagnosis of acute myeloid leukemia (AML), with 74% blasts present. He started his induction chemotherapy treatment, 7  +  3, seven days of cytarabine, and three days of daunorubicin (see Table 11.1). Mitchell’s hospital stay for his induction therapy was approximately 4 weeks. He would have very little memory of his induction period. Mitchell: I barely remember anything; I remember fevers, ice bags, lots of tubes of blood and multiple tests … I think in a way I just kind of blocked things out and focused on getting through the weirdest part.

Mitchell was extremely fatigued during his induction period. He tried to focus on getting through the chemotherapy. He had a very difficult time sleeping, and when remembering this time he explained: “I felt like my brain was playing 5 movies at once; it’s like I was dreaming and awake at the same time.”

As the induction period wore on, Mitchell’s view of himself shifted dramatically: “I went from being a normal working person to a person who spent a month in the hospital. So, that’s when I went from being normal to being in a bed, a huge shock to the system.”

Fourteen days after an initial bone marrow biopsy and intense induction period, no features of leukemia involvement were seen. After recovery of his blood counts and another bone marrow biopsy that showed remission, Mitchell proceeded to consolidation therapy (Table 11.2). Mitchell underwent two cycles of high-dose cytarabine (HiDAC) for his consolidation therapy. Mitchell had another bone marrow biopsy prior to his next step of receiving an allogeneic stem cell transplant to confirm he was still free of disease. Table 11.1  Induction chemotherapy 7 + 3 induction Daunorubicin IV 5 min push Days 1 to 3 Cytarabine 24 hour IV Days 1 to 7 Side effects: Daunorubicin—cardiotoxicity, hyperuricemia, stomatitis Cytarabine—nausea, diarrhea, drug fever, drug rash, mucositis, tumor lysis syndrome

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Table 11.2  Consolidation chemotherapy HiDAC consolidation Cytarabine IV 3 hours every other day, Days 1, 3, and 5 Prednisone eye drops given every 6 hours to protect against corneal toxicity Side effects: Cerebellar toxicity, diarrhea, drug rash, drug fever, nausea, mucositis, tumor lysis syndrome, respiratory distress syndrome, and Cytarabine syndrome.

Compared to other treatment approaches, allogeneic stem cell transplantation is associated with a higher rate of side effects and mortality in patients. However, it is considered for patients with high-risk AML, based on cytogenetics and molecular test results. Mitchell, unfortunately, was diagnosed with high-risk AML based on his cytogenetics. Mitchell had heard of people receiving stem cell transplants but really didn’t know about them: “it’s one of those things you never really think of, but if that’s what needs to be done and it’s your next step in survival, you just do it regardless of what could happen.”

Allogeneic stem cell transplant is the process of infusing healthy donor stem cells into a recipient after administering “conditioning” chemotherapy to prevent rejection of these cells. Allogeneic transplant uses pluripotent hematopoietic stem cells (HSCs) from a related or unrelated donor as the source of stem cells. These cells are used to replace the diseased bone marrow of cancer patients with AML and other hematologic malignancies. Donors are identified through “HLA typing” to match certain human leukocyte antigens. HLA typing is complex. HLA proteins are located on the surface of most cells in the body. They make up a person’s tissue type, which varies from person to person. A close match between a donor and recipient at specific HLA loci is essential for a successful transplant outcome. HLA matching reduces the risk of a post-­transplant complication called graft-versus-host disease (GVHD). Mitchell was preparing for his admission to undergo his allogeneic stem cell transplant. He had recently moved to Lebanon, NH, to be closer to the hospital for follow-up treatment after transplant. While he readied himself for the days ahead, there were worries unrelated to the transplant on his mind: “I was prepared, I had been through four rounds of chemo. I had spent a lot of time here; I felt everyone had pretty much let me know what was going on. My real issues were like insurance and work-related stuff.”

The transplant coordinator and physician met with Mitchell and Heather. They reviewed the risks and benefits associated with transplantation, including the issues of GVHD and graft rejection. The coordinator and physician also emphasized both the physical and emotional needs that would be required going forward and over the

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next nine months and possibly indefinitely, thereafter. When asked about his thoughts and fears about the transplant, Mitchell shared: “I don’t know that I really had a worst fear. I had already known transplant was going to be part of the treatment when I was diagnosed, and through induction therapy it was talked about. The worst part is being dead, so anything is better than that. So, you know I’d already beaten the curve so there’s really no worst fear.”

The anticipated day arrived, and the nurse educated in transplant introduced herself to Mitchell and Heather. She went on to explain the admission process. She completed all the chemotherapy calculations and confirmed all the orders were accurate and appropriate. Mitchell felt comfortable and informed when he was admitted for his myeloablative matched unrelated donor (MUD) allogeneic stem cell transplant. Six months after his first symptoms, he was now facing another life-changing event. In May, he began the conditioning regimen of myeloablative fludarabine/busulfan/ATG and methotrexate. When Mitchell arrived at the Hematology Special Care Unit (HSCU) after the placement of his triple lumen central line, the nurse made a chart of the conditioning treatment on his whiteboard (Table 11.3). Mitchell really liked the plans mapped out on his whiteboard daily, as follows: The nurse explained to Mitchell his conditioning therapy, while she mapped it out on his whiteboard. Mitchell was educated about the side effects of the conditioning therapy and the pre-medications he was going to receive to help prevent these side effects, and he was encouraged to ask questions at any time. The nurse verified that Mitchell had taken his loading dose of 400  mg phenytoin in the morning prior to admission. Phenytoin is given prophylactically to prevent seizures, a potential side effect of busulfan. Mitchell settled into his room and he was scheduled to receive fludarabine on the first afternoon, with the potential side effects of nausea, vomiting, diarrhea, mucositis, and immune suppression. He was also started on his veno-occlusive disease (VOD) prophylaxis, with ursodiol and enoxaparin, due to his risk for VOD, based on the fact that busulfan is metabolized by the liver and a ferritin level of 1200, combined with iron overload. On Day −6 Mitchell began both busulfan and antithymocyte globulin (ATG). The nurse confirmed the start times of the IV fluids and pre-medications. Busulfan was given Day −6 through Day −3, with phenytoin seizure prophylaxis, as above, for other potential side effects including lung toxicity, fatigue, poor appetite, nausea, vomiting, and diarrhea. ATG is an immunosuppressive agent that aids in the prophylaxis of graft-versus-­ host disease. ATG is given Day −6 through Day −4 over 10 hours. Pre-medications are given: tylenol 650 mg and diphenhydramine 50 mg, 30 minutes prior to the start of ATG and 5 hours into the administration. ATG is derived from either horse or rabbit sources, and a variety of toxicities may occur, such as fever, chills, rigors,

Day −6 Fludarabine @ 0900

Day −5 Fludarabine @ 0900

IV fluids 2 hours prior IVF continuous to busulfan Orders Busulfan Busulfan Checked by 2 @ 1000 @ 1000 BMT RN Pre-meds ATG pre-medications ATG pre-medications Fludarabine 10-hour 10-hour Rabbit ATG Rabbit ATG VOD Repeat pre-meds in Repeat pre-meds in Prophylaxis 5 hours 5 hours started Monitor closely Monitor closely Hypersensitivity Hypersensitivity reaction reaction

Admit

Day −7 Line Placement

Table 11.3  Conditioning chemotherapy

Monitor closely Hypersensitivity reaction

ATG pre-medications 10-hour Rabbit ATG Repeat pre-meds in 5 hours

Busulfan @ 1000

IVF continuous

Day −4 Fludarabine @ 0900

Monitor I/O closely

IVF continuous Busulfan @ 1000

Day −3 Fludarabine @ 0900

Monitor I/O closely

Day −2 Oral Tacrolimus begins

Monitor I/O closely

Day −1 Verify with cellular therapy Time/number of cell bags

Monitor closely Hypersensitivity reaction

Post-hydration

Infusion of fresh cells

Pre-medications

4 hours of hydration

Day 0 Review stem cell infusion checklist

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hypotension, and capillary leak syndrome. Although many of the toxicities are manageable, the severity and frequency of toxicities are greatest on the first day of administration. Mitchell tolerated his conditioning therapy without complications. Day −1 was utilized as a rest day. The day was spent educating him on the stem cell infusion planned for day 0 and coordinating the time of the infusion. Mitchell received his stem cell transplant, Day 0, as mapped out on his whiteboard. He had a febrile non-hemolytic transfusion reaction when receiving his cells. He then was monitored for infection related to developing a fever when receiving his stem cells. He remained on cefepime for functional neutropenic fevers with infectious workup initiated. This workup was positive for clostridium difficile colitis, which was treated with vancomycin 500 mg QID, later titrated down to 125 mg QID given clinical improvement. Unfortunately, this also meant that Mitchell was confined to his room for contact precautions. He focused on getting back to normal and getting out of the hospital: “I was bored out of my mind; I was glad I brought a tablet. I read a couple of books on barbecuing and watched a lot of videos on cooking. The worst thing was I ended up with C- diff, so I was pretty much confined to my room for most of the stay, being stuck in my room was hard.”

Mitchell received methotrexate on days +1, +3, +6, and day +11. Methotrexate is given for the prevention of acute graft versus host disease. Some side effects include myelosuppression, mucositis, interstitial pneumonitis, hepatotoxicity, and nephrotoxicity. Filgrastim was initiated on Day +7 and continued until count recovery. He experienced low back pain and received tramadol and daily loratadine with good effect. Mitchell struggled with being confined to his room during his transplant stay: “It’s the same routine between 6 and 7, you get the morning check and then you have coffee, then you have vitals then you wait around for lunch, and then vitals and then you wait around for dinner, then vitals and just a lot of waiting.”

On Day +2, the RN made plans with Mitchell that afternoon to begin to review the discharge handout. He was instructed to read through the handout and highlight areas that he had questions about for review with him during the remainder of his hospital stay. Mitchell’s ANC slowly decreased to