Cord Blood
Establishing a National Hematopoietic Stem Cell Bank Program
Emily Ann Meyer, Kathi Hanna, and Kristine Gebbie, Editors
THE NATIONAL ACADEMIES PRESS
Washington, D.C.
www.nap.edu
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NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance.
This study was supported by contract number HHSH25056028 between the Department of Health and Human Services and the National Academy of Sciences. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the views of the organizations or agencies that provided support for this project.
Library of Congress Cataloging-in-Publication Data
Institute of Medicine (U.S.). Committee on Establishing a National Cord Blood Stem Cell Bank Program.
Cord blood : establishing a national hematopoietic stem cell bank program / Committee on Establishing a National Cord Blood Stem Cell Bank Program, Board on Health Sciences Policy ; Emily Ann Meyer, Kathi Hanna, and Kristine Gebbie, editors.
p. ; cm.
“This study was supported by contract number HHSH25056028 between the Department of Health and Human Services and the National Academy of Sciences.”
Includes bibliographical references and index.
ISBN 0-309-09586-7 (hardcover)—ISBN 0-309-09644-8
1. Fetal blood—Transplantation. 2. Hematopoietic stem cells. 3. Blood banks. I. Meyer, Emily Ann. II. Hanna, Kathi E. III. Gebbie, Kristine M. IV. Title.
[DNLM: 1. Cord Blood Stem Cell Transplantation—standards.
2. Blood Banks—organization & administration. 3. Blood Grouping and Crossmatching—standards. 4. Hematopoietic Stem Cell Transplantation—ethics. 5. Hematopoietic Stem Cell Transplantation—legislation & jurisprudence. 6. Hematopoietic Stem Cell Transplantation—standards. WH 380 I604c 2005]
RM171.I54 2005
362.17′84—dc22
2005018345
Additional copies of this report are available from the
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Copyright 2005 by the National Academy of Sciences. All rights reserved.
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THE NATIONAL ACADEMIES
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COMMITTEE ON ESTABLISHING A NATIONAL CORD BLOOD STEM CELL BANK PROGRAM
KRISTINE M. GEBBIE (Chair), Associate Professor of Nursing,
Columbia University, New York
WADE M. AUBRY, Senior Advisor,
Health Technology Center, San Francisco, California
RICHARD CHAMPLIN, Chairman,
Department of Blood and Marrow Transplantation, University of Texas, Houston
JAMES F. CHILDRESS, Director,
Institute for Practical Ethics, University of Virginia, Charlottesville
CHARLES FISKE, Senior Executive,
Brockton Area Multi-Services, Inc., Bridgewater, Massachusetts
ROBERT D. GIBBONS, Director,
Center for Health Statistics, University of Illinois at Chicago
N. REBECCA HALEY, Vice President,
Medical and Regulatory Affairs, StemCo Biomedical, Inc., Durham, North Carolina
MARY M. HOROWITZ, Scientific Director,
International Bone Marrow Transplant Registry, Medical College of Wisconsin, Milwaukee
SUZANNE T. ILDSTAD, Director,
Institute for Cellular Therapeutics, University of Louisville, Kentucky
LINDA L. KELLEY, Director,
Department of Medicine, University of Utah School of Medicine, Salt Lake City
J. MICHAEL McGINNIS, Counselor to the President,
The Robert Wood Johnson Foundation, Washington, DC
DAVID MELTZER, Assistant Professor,
General Internal Medicine, University of Chicago, Illinois
KENNETH J. MOISE, JR., Professor,
Obstetrics and Gynecology, University of North Carolina, Chapel Hill
LARRY I. PALMER, Professor,
University of Louisville, Kentucky
DAVID T. SCADDEN, Director,
Center for Regenerative Medicine and Technology, Massachusetts General Hospital, Boston
JOHN E. WAGNER, Professor,
Pediatrics, University of Minnesota, Minneapolis
ANDREW M. YEAGER, Professor,
School of Medicine, University of Pittsburgh, Pennsylvania
IOM Project Staff
Emily Ann Meyer, Study Director
Shira H. Fischer, Research Associate
Benjamin Hamlin, Research Associate
Judith Estep, Senior Project Assistant
Consultant
Kathi Hanna, Science Writer/Editor
BOARD ON HEALTH SCIENCES POLICY
PHILIP PIZZO, (Chair),
Stanford University, Palo Alto, California
LESLIE BENET,
University of California, San Francisco
DAVID BLUMENTHAL,
Harvard Medical School, Boston, Massachusetts
GAIL H. CASSELL,
Eli Lilly and Company, Indianapolis, Indiana
ELLEN WRIGHT CLAYTON,
Vanderbilt University, Nashville, Tennessee
DAVID COX,
Perlegen Sciences, Santa Clara, California
NANCY DUBLER,
Montefiore Medical Center, The Albert Einstein College of Medicine, Bronx, New York
ROBERT GIBBONS,
University of Illinois at Chicago
LYNN R. GOLDMAN,
Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland
BERNARD GOLDSTEIN,
University of Pittsburgh, Pennsylvania
MARTHA N. HILL,
Johns Hopkins University School of Nursing, Baltimore, Maryland
ALAN LESHNER,
American Association for the Advancement of Science, Washington, DC
DANIEL MASYS,
University of California, San Diego
JONATHAN MORENO,
University of Virginia, Charlottesville
E. ALBERT REECE,
College of Medicine, University of Arkansas, Little Rock
MYRL WEINBERG,
National Health Council, Washington, D.C.
MICHAEL J. WELCH,
Washington University School of Medicine, St. Louis, Missouri
MARY WOOLLEY,
Research!America, Alexandria, Virginia
IOM Council Liaison
BERNARD LO,
University of California, San Francisco
IOM Board on Health Sciences Policy Staff
Andrew M. Pope, Director
Amy Haas, Administrative Assistant
Carlos Gabriel, Financial Associate
INDEPENDENT REPORT REVIEWERS
This report has been reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise, in accordance with procedures approved by the National Research Council’s Report Review Committee. The purpose of this independent review is to provide candid and critical comments that will assist the institution in making its published report as sound as possible and to ensure that the report meets institutional standards for objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process. We wish to thank the following individuals for their review of this report:
Harvey J. Alter, Department of Transfusion Medicine, National Institutes of Health, Bethesda, Maryland
Fredrick R. Appelbaum, Fred Hutchinson Cancer Research Center, Seattle, Washington
Ellen Areman, Division of Cell and Gene Therapies, United States Food and Drug Administration, Center for Biologics Evaluation and Research, Rockville, Maryland
Mary Banfill, Michigan Community Blood Centers, Grand Rapids, Michigan
Lee Ann Baxter-Lowe, University of California at San Francisco Immunogenetics Lab, San Francisco, California
Ellen Wright Clayton, Genetics and Health Policy Center, Vanderbilt University, Nashville, Tennessee
Michael F. Greene, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, Massachusetts
Liana Harvath, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland
Armand Keating, Department of Medical Oncology and Hematology, Princess Margaret Hospital, Ontario Cancer Institute, Toronto, Ontario, Canada
Eric M. Meslin, Indiana University Center for Bioethics
Joana Ramos, Cancer Resources & Advocacy, Seattle, Washington
Harold C. Sox, American College of Physicians of Internal Medicine, Philadelphia, Pennsylvania
Mark Votruba, Department of Economics, Case Western Reserve University, Cleveland, Ohio
David A. Williams, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio
Charles B. Wilson, Health Technology Center, San Francisco, California
Although the reviewers listed above have provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations nor did they see the final draft of the report before its release. The review of this report was overseen by Nancy Ascher, Professor and Chair of the Department of Surgery, University of California, San Francisco, and Enriqueta Bond, President, Burroughs Wellcome Fund, Research Triangle Park, North Carolina. Appointed by the National Research Council and Institute of Medicine, they were responsible for making certain that an independent examination of this report was carried out in accordance with institutional procedures and that all review comments were carefully considered. Responsibility for the final content of this report rests entirely with the authoring committee and the institution.
PREFACE
An effective National Cord Blood Stem Cell Bank Program should take into account current and future science; the needs of patients, physicians and donors; quality assurance; and outcomes assessment. Balancing of all these perspectives presents a substantial challenge, and tensions among current organizations active in the field led, in part, to the request for this report from the Institute of Medicine and formed a background for all of the committee’s information gathering and deliberations.
The small number of extremely knowledgeable specialists in this field—many of whom have very close ties to at least one of the major participants in the organizational debate—meant that in order to ensure inclusion of all important perspectives on equity, access, and outcomes, membership on the committee changed several times. Although the changes ensured an extremely rich range of viewpoints, it may have confused some observers.
The following truths regarding cord blood collection and transplantation became apparent at the first meeting and informed the committee’s discussions and recommendations throughout the study:
-
The goal of ensuring the best care for patients requires that transplant physicians be provided with timely, complete, and accurate information on available hematopoietic stem cells from both adult donors and umbilical cord blood at the time of decision making about a transplant. Information about bone marrow donor programs and experiences had to be considered.
-
Quality assurance for the collection, storage, and use of cord blood is essential, as is a coordinated approach to the collection of complete information on the outcomes of all hematopoietic stem cell transplants.
The committee appreciates the generosity of the many bankers, transplant physicians, transplant recipients, and scientists who shared their experiences and data during open meetings and site visits and in correspondence with the committee. Invaluable knowledge was gained, none of which could have been fully assimilated without the assistance of the very able staff supporting this report.
Finally, a fully coordinated quality national system to support hematopoietic stem cell transplantation cannot be accomplished by any one action or organization. This report includes both a discussion of what such a system should look like when it is complete and focuses on the key steps that respond to immediate concerns and move toward the long-term goal. The interested community is urged to keep the goal of comprehensive support for hematopoietic stem cell transplantation in mind while struggling with the inevitably messy process of arriving at that point. The committee’s overall goal of a seamless program of access to hematopoietic stem cells points directly to a single national program encompassing the existing marrow donor programs and this cord blood program. Providing meaningful recommendations on how to accomplish such a program, however, would have required study of the existing National Marrow Donor Program and other adult hematopoietic progenitor cell programs and the ways to merge them with the specifics of a cord blood program well in excess of the time and resources available to the committee. For that reason, the report highlights the need for coordination at many points, expects analysis of outcomes from all sources of cells, leaves the door open to contractual arrangements with core components of the existing program when consistent with policy direction, and anticipates that the question of full integration will be dealt with in the future.
Kristine M. Gebbie
Chair
ACKNOWLEDGMENTS
The committee wishes to acknowledge the valuable contributions that were made to this study by many individuals who shared their expertise with the committee. Special thanks go to James Burdick, Shelly Carter, Jeffrey Chell, Phil Coelho, Dennis Confer, Jeff Couglin, Michael Fitzpatrick, Captain Robert Hartzman, Liana Harvath, Valerie Hurt, Brent Jaquet, Naynes Kamani, Joanne Kurtzberg, Ellen Lazarus, David Leitch, Pam Murph, Sudip Parikh, Pablo Rubinstein, Karen Shoos-Lipton, Edward Snyder, Cladd Stevens, Susan Stewart, Phyllis Warkentin, Jill Warner, Elizabeth Wagner, and Thomas Weignand.
We would also like to thank the following banks, which graciously allowed the committee to tour their facilities: CyroBanks International, New York Blood Center, Children’s Hospital Oakland, Cord Blood Registries, St. Louis Cord Blood Bank, J.P. McCarthy Cord Stem Cell Bank, and Michigan Community Blood Centers Cord Blood Bank.
The committee would also like to thank the commissioned paper authors, whose contributions assisted greatly in the understanding and thorough evaluation of the subject: Karen Ballen, Robert Gibbons, Margaret Goodell, David H. Howard, and Carolyn Katovich Hurley.
Thanks also go to Siddarth Puram, who worked as an intern the summer of 2004 and provided extensive help in compiling and summarizing literature and in the development and distribution of the cord blood bank survey.
Finally, the committee would like to thank Philip Pizzo and the Board on Health Sciences Policy for their oversight and the IOM staff: Judy Estep,
LIST OF TABLES, FIGURES, AND BOXES
TABLES
ES-1 |
Key Functions of a National Cord Blood Program, |
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1-1 |
Views from NYBC and NMDP on an Ideal National Stem Cell Cord Blood Bank Program, |
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2-1 |
Indications for Allogeneic and Autologous Stem Cell Support, |
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3-1 |
Genetic Diseases Treatable by Transplantation of Cord Blood, |
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3-2 |
Summary of Current Research, |
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4-1 |
Cord Blood Banking Options, |
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4-2 |
FDA Regulation of Human Cells, Tissues, and Cellular and Tissue-Based Products, |
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5-1 |
Consent Practices for Agencies Currently Involved with Cord Blood, |
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6-1 |
Model of Inventory Costs, |
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7-1 |
Key Functions of a National Cord Blood Program, as Envisioned by the Institute of Medicine Committee, |
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C-1 |
Banks That Responded, |
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C-2 |
Type of Bank, |
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C-3 |
Self-Reported Accreditation, |
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C-4 |
Numbers of Collected, Stored, and Transplanted Units, |
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C-5 |
Banks Which Are Currently Collecting Units, |
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C-6 |
Racial Makeup of Inventory, |
C-7 |
Criteria to Determine Which Units Are Suitable for Banking, |
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C-8 |
Criteria Used to Determine Which Units Are for Transplant, |
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C-9 |
Units That Are Not Useable for Transplant, |
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C-10 |
Are Units Bar Coded and Tracked Electronically? If Not, How Are They Tracked?, |
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C-11 |
Informatics, |
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C-12 |
Collection and Storage: Who Does the Collection, |
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C-13 |
Exclusion Criteria, |
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C-14 |
Screening Completed Prior to Storage, |
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C-15 |
Number of Units Collected and Shipped by Year, |
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C-16 |
Costs, |
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C-17 |
Funding of Public Banks, |
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C-18 |
Neonatal Health Status Follow-Up, |
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C-19 |
How the Units Are Stored, |
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D-1 |
Donor Cell Contribution to Nonhematopoietic Tissues After Whole Bone Marrow Transplantation in Animal Models, |
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D-2 |
Circulating Cell Contribution to Nonhematopoietic Tissues in Clinical Specimens, |
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E-1 |
Match Probabilities for Adults Age ≥20, |
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E-2 |
Match Probabilities for Pediatric Patients Age <20, |
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E-3 |
Projected Number of Annual Transplants by Cord Blood Inventory Level, |
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E-4 |
Life Years Gained from Marrow and Cord Transplantation, |
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E-5 |
Cost Model Parameters, |
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E-6 |
Cost Estimates by Inventory Level, |
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E-7 |
Cost per Life Year Gained as a Function of Cord Inventory, |
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E-8 |
Match Probabilities by Race, |
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E-9 |
Sensitivity Analysis, |
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F-1 |
Alleles Identified at Each HLA Locus as of January 2005, |
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F-2 |
DRB1*03 Allele Frequencies in Various U.S. Populations, |
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F-3 |
Examples of Relationships Between Serologically Defined Antigens and DNA-Defined Types, |
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F-4 |
Examples of Alleles Which Encode Specific HLA Proteins (or Antigens), |
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F-5 |
Examples of the Types of Volunteers Carrying the Same Allele, A*0201, |
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F-6 |
Matches for a Patient Typed a A*0201, A*3201, B*0702, B*1501, Cw*0401, Cw*0702, DRB1*0101, DRB1*0302, |
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F-7 |
Possible Allele Assignment of Individual Typed as 6 of 6 Antigen Match, A2, A32, B7, B62, DR1, DR3, for a Patient Typed as A*0201, A*3201, B*0702, B*1501, Cw*0401, Cw*0702, DRB1*0101, DRB1*0302, |
F-8 |
Examples of HLA Typing Assignments Carried by Volunteer Donors on Registries, |
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F-9 |
Steps in Donor Selection, |
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F-10 |
Summary of HLA Matches at Each Locus in 6/6 Antigen Matched Donor-Recipient Pairs (n = 1422) from NMDP, |
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F-11 |
Summary of HLA Matches at Each Locus in 5/6 Antigen Matched Donor-Recipient Pairs (n = 429), |
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G-1 |
Summary Statistics Predictors by Outcomes (n = 755 Transplants), |
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G-2 |
Maximum Likelihood Estimates, Standard Errors, and Probabilities Main Effects Model, |
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G-3 |
Estimated (Observed) Cumulative Competing Risk Survival Functions Proportion Experiencing the Event, |
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G-4 |
Summary Statistics Cell Dose, Age, and HLA Mismatch, Number (Percent) of Patients (n = 755 Transplants), |
FIGURES
ES-1 |
Proposed structure of a national program, |
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2-1 |
Formation of the multiple peripheral blood cells from multipotent hematopoietic stem cells, |
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2-2 |
The human histocompatibility genes, |
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4-1 |
Major components in the process of cord blood collection, banking, and transplantation, |
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4-2 |
Example of storage container for cryopreservation of cord blood units, |
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4-3 |
Algorithm for selection of bone marrow versus umbilical cord blood for patients more than 20 years of age, |
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4-4 |
Algorithm for selection of bone marrow versus umbilical cord blood for patients less than 20 years of age, |
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7-1 |
The relationships that the IOM committee envisions under the governance structure described in its recommendations, |
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C-1 |
Total units collected, by bank, |
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C-2 |
Available units—across all banks, |
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C-3 |
Units collected and shipped, by year, |
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E-1 |
Search strategy for patients age ≥20, |
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E-2 |
Search strategy for patients age >20, |
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E-3 |
Total life years for 8,200 transplant candidates as a function of cord inventory, |
F-1 |
Human histocompatibility genes, |
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G-1 |
Cumulative proportion alive (engrafted) (TNC/kg < 2.5 × 107), |
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G-2 |
Cumulative proportion alive (engrafted) (TNC/kg = 2.5 − 5.0 × 107), |
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G-3 |
Cumulative proportion alive (engrafted) (TNC/kg > 5.0 × 107), |
BOXES
ES-1 |
Summary of Recommendations for Establishing a National Cord Blood Stem Cell Bank Program, |
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2-1 |
HLA and HLA Matching, |
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2-2 |
Stratification Variables for the COBLT Study, |
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3-1 |
Examples of Effective Clinical Use of Cord Blood in Treating Inherited Diseases, |
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A-1 |
Site Visits Conducted by the Committee (by date of visit), |