HLA Match Likelihoods for Hematopoietic Stem-Cell Grafts in the U.S. Registry

Loren Gragert(National Marrow Donor Program), Mary Eapen, Eric Williams(National Marrow Donor Program), John L. Freeman(National Marrow Donor Program), Stephen R. Spellman, Robert L. Baitty(Health Resources and Services Administration), Robert J. Hartzman(Naval Medical Research Command), J. Douglas Rizzo, Mary M. Horowitz, Dennis L. Confer(National Marrow Donor Program), Martin Maiers(National Marrow Donor Program)
New England Journal of Medicine
July 23, 2014
Cited by 1,089Open Access
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Abstract

BACKGROUND: Hematopoietic stem-cell transplantation (HSCT) is a potentially lifesaving therapy for several blood cancers and other diseases. For patients without a suitable related HLA-matched donor, unrelated-donor registries of adult volunteers and banked umbilical cord-blood units, such as the Be the Match Registry operated by the National Marrow Donor Program (NMDP), provide potential sources of donors. Our goal in the present study was to measure the likelihood of finding a suitable donor in the U.S. registry. METHODS: Using human HLA data from the NMDP donor and cord-blood-unit registry, we built population-based genetic models for 21 U.S. racial and ethnic groups to predict the likelihood of identifying a suitable donor (either an adult donor or a cord-blood unit) for patients in each group. The models incorporated the degree of HLA matching, adult-donor availability (i.e., ability to donate), and cord-blood-unit cell dose. RESULTS: Our models indicated that most candidates for HSCT will have a suitable (HLA-matched or minimally mismatched) adult donor. However, many patients will not have an optimal adult donor--that is, a donor who is matched at high resolution at HLA-A, HLA-B, HLA-C, and HLA-DRB1. The likelihood of finding an optimal donor varies among racial and ethnic groups, with the highest probability among whites of European descent, at 75%, and the lowest probability among blacks of South or Central American descent, at 16%. Likelihoods for other groups are intermediate. Few patients will have an optimal cord-blood unit--that is, one matched at the antigen level at HLA-A and HLA-B and matched at high resolution at HLA-DRB1. However, cord-blood units mismatched at one or two HLA loci are available for almost all patients younger than 20 years of age and for more than 80% of patients 20 years of age or older, regardless of racial and ethnic background. CONCLUSIONS: Most patients likely to benefit from HSCT will have a donor. Public investment in donor recruitment and cord-blood banks has expanded access to HSCT. (Funded by the Office of Naval Research, Department of the Navy, and the Health Resources and Services Administration, Department of Health and Human Services.).


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