EXPLORING THE STATE OF THE SCIENCE OF
STEM CELL TRANSPLANTATION
AND POSTTRANSPLANT DISABILITY

PROCEEDINGS OF A WORKSHOP

Laura Aiuppa Denning and Erin Hammers Forstag, Rapporteurs

Board on Health Care Services

Health and Medicine Division

THE NATIONAL ACADEMIES PRESS
Washington, DC
www.nap.edu

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This activity was supported by a contract between the National Academy of Sciences and the U.S. Social Security Administration. Any opinions, findings, conclusions, or recommendations expressed in this publication do not necessarily reflect the views of any organization or agency that provided support for the project.

International Standard Book Number-13: 978-0-309-68676-1
International Standard Book Number-10: 0-309-68676-8
Digital Object Identifier: https://doi.org/10.17226/26541

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Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2022. Exploring the state of the science of stem cell transplantation and posttransplant disability: Proceedings of a workshop. Washington, DC: The National Academies Press. https://doi.org/10.17226/26541.

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PLANNING COMMITTEE ON THE STATE OF THE SCIENCE OF HEMATOPOIETIC STEM CELL TREATMENT AND DISABILITY¹

SARA ROSENBAUM (Chair), Harold and Jane Hirsh Professor, George Washington University

FREDERICK R. APPELBAUM, Professor, Deputy Director, Fred Hutchinson Cancer Research Center

MARGARET BEVANS, U.S. Public Health Service Director, Office of Research Nursing Office of the Clinical Director, Division of Intramural Research, National Institutes of Health

JAMES BOWMAN, Physician, Division of Transplantation, Health Resources and Services Administration

CYNTHIA E. DUNBAR, Chief, Translational Stem Cell Biology Branch, NIH Distinguished Investigator, National Heart, Lung, and Blood Institute, National Institutes of Health

MARY M. HOROWITZ, Robert A. Uihlein, Jr. Chair in Hematologic Research, Deputy Cancer Center Director, Medical College of Wisconsin; Scientific Director Emeritus, Center for International Blood and Marrow Transplant Research

LESLIE S. KEAN, Director, Stem Cell Transplant Center, Robert A. Stranahan Professor of Pediatrics, Harvard Medical School

DAVID T. SCADDEN, Gerald and Darlene Jordan Professor of Medicine, Department of Stem, Cell and Regenerative Biology, Harvard Stem Cell Institute, Center for Regenerative Medicine, Massachusetts General Hospital

ALEXIS A. THOMPSON, Sarah and A. Watson Armour Chair in Childhood Cancer and Blood Disorders, Hematology Section Head, Ann & Robert H. Lurie Children’s Hospital of Chicago; Professor of Pediatrics, Feinberg School of Medicine, Northwestern University

Health and Medicine Division Staff

LAURA AIUPPA DENNING, Senior Program Officer

ADRIENNE FORMENTOS, Research Associate

___________________

¹ The National Academies of Sciences, Engineering, and Medicine’s planning committees are solely responsible for organizing the workshop, identifying topics, and choosing speakers. The responsibility for the published Proceedings of a Workshop rests with the workshop rapporteurs and the institution.

RUKSHANA GUPTA, Research Assistant

SHARYL NASS, Senior Director, Board on Health Care Services

Consultant

ERIN HAMMERS FORSTAG, Consulting Writer

Reviewers

This Proceedings of a Workshop was reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise. The purpose of this independent review is to provide candid and critical comments that will assist the National Academies of Sciences, Engineering, and Medicine in making each published proceedings as sound as possible and to ensure that it meets the institutional standards for quality, objectivity, evidence, and responsiveness to the charge. The review comments and draft manuscript remain confidential to protect the integrity of the process.

We thank the following individuals for their review of this proceedings:

Although the reviewers listed above provided many constructive comments and suggestions, they were not asked to endorse the content of the proceedings nor did they see the final draft before its release. The review of this proceedings was overseen by KENNETH CARL ANDERSON, Dana Farber Cancer Institute. He was responsible for making certain that an independent examination of this proceedings was carried out in accordance with standards of the National Academies and that all review comments were carefully considered. Responsibility for the final content rests entirely with the rapporteurs and the National Academies.

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Acknowledgments

The National Academies of Sciences, Engineering, and Medicine’s Board on Health Care Services wishes to express its sincere gratitude to the planning committee chair, Sara Rosenbaum, for her valuable contributions to the development and orchestration of this workshop. The board also wishes to thank all the members of the planning committee, who collaborated to ensure a workshop replete with informative presentations and moderated rich discussions. Finally, the board wants to thank the speakers, who generously shared their expertise and their time with workshop participants. Funding from the Social Security Administration made this workshop possible.

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Contents

ACRONYMS AND ABBREVIATIONS

1 INTRODUCTION

Background

2 OVERVIEW OF HEMATOPOIETIC STEM CELL TRANSPLANTATION AND DISABILITY IN THE UNITED STATES

Understanding Stem Cell Transplantation

Patterns of Recovery

Discussion

3 LATE EFFECTS OF HEMATOPOIETIC STEM CELL TRANSPLANTATION

Immune Recovery in Patients

Graft-Versus-Host Disease

Considerations for Children and Adolescents

Discussion

4 HEMATOPOIETIC STEM CELL TRANSPLANTATION SURVIVORSHIP

Patient and Caregiver Experiences

Assessment and Intervention

Discussion

5 THE FUTURE OUTLOOK FOR STEM CELL TRANSPLANTATION AND DISABILITY

Gene Therapy

CAR T-Cell Therapy

Preventing and Mitigating Hematopoietic Stem Cell Transplantation Complications

Discussion

Closing Remarks

APPENDIXES

A REFERENCES

B WORKSHOP AGENDA

C BIOGRAPHICAL SKETCHES OF WORKSHOP PLANNING COMMITTEE MEMBERS AND SPEAKERS

Boxes, Figures, and Tables

BOXES

1-1 Statement of Task

1-2 Key Points by Individual Speakers and Participants

FIGURES

2-1 Annual number of hematopoietic stem cell transplant recipients in the United States by transplant type

2-2 Relapse or progression after allogeneic hematopoietic stem cell transplantation for hematologic malignancies in U.S. patients under 60 years, 2015–2019

2-3 Overall survival after autologous hematopoietic stem cell transplantation for U.S. patients under 60 years, 2015–2019

2-4 Attributable disability after hematopoietic stem cell transplantation

2-5 Physical and mental functioning following hematopoietic stem cell transplantation

2-6 Physical limitations after hematopoietic stem cell transplantation in patients with and without depression prior to the transplant

2-7 Self-reported recovery outcomes following hematopoietic stem cell transplantation

2-8 Potential comorbidities and late effects following hematopoietic stem cell transplantation

3-1 Causes of death by treatment arm

3-2 Nonrelapse mortality after hematopoietic stem cell transplantation

3-3 Chronic graft-versus-host disease–related disability

3-4 Number of late effects from hematopoietic stem cell transplantation before death or at 5 years

4-1 Conceptual model of palliative care interventions for patients receiving a hematopoietic stem cell transplant

4-2 Sustained effects of palliative care interventions 6 months after hematopoietic stem cell transplantation

5-1 Historical overview of hematopoietic stem cell transplantation gene therapy

5-2 Disparities in human leukocyte antigen match rates by race

TABLES

2-1 Diseases Treatable with Hematopoietic Stem Cell Transplantation

2-2 Studies Examining Return to Work After Hematopoietic Stem Cell Transplantation

3-1 Similarities and Differences in Clinical Factors Influencing Disability in Children and Adults Who Receive Hematopoietic Stem Cell Transplants

3-2 Diagnoses Associated with High Burden of Late Disability

5-1 CAR T Cells for B-Cell Malignancies

5-2 Increase in Use of Posttransplant Cyclophosphamide in Patients Receiving Hematopoietic Stem Cell Transplants

Acronyms and Abbreviations