High-resolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation

Stephanie J. Lee(Fred Hutch Cancer Center), John P. Klein(Medical College of Wisconsin), Michael Haagenson(National Marrow Donor Program), Lee Ann Baxter‐Lowe(University of California, San Francisco), Dennis L. Confer(National Marrow Donor Program), Mary Eapen(Medical College of Wisconsin), Marcelo Fernández-Viña(The University of Texas MD Anderson Cancer Center), Neal Flomenberg(Thomas Jefferson University Hospital), Mary M. Horowitz(Medical College of Wisconsin), Carolyn Katovich Hurley(Georgetown University), Harriet Noreen(University of Minnesota Medical Center), Machteld Oudshoorn(Europdonor Foundation), Effie W. Petersdorf(Fred Hutch Cancer Center), Michelle Setterholm(National Marrow Donor Program), Stephen R. Spellman(National Marrow Donor Program), Daniel Weisdorf(University of Minnesota), Thomas Williams(University of New Mexico), Claudio Anasetti(Moffitt Cancer Center)
Blood
September 4, 2007
10.1182/blood-2007-06-097386
Cited by 1,237Open Access
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Abstract

The relative importance of various human leukocyte antigen (HLA) loci and the resolution level at which they are matched has not been fully defined for unrelated donor transplantation. To address this question, National Marrow Donor Program data from 3857 transplantations performed from 1988 to 2003 in the United States were analyzed. Patient-donor pairs were fully typed for HLA-A, -B, -C, -DRB1, -DQB1, -DQA1, -DPB1, and -DPA1 alleles. High-resolution DNA matching for HLA-A, -B, -C, and -DRB1 (8/8 match) was the minimum level of matching associated with the highest survival. A single mismatch detected by low- or high-resolution DNA testing at HLA-A, -B, -C or -DRB1 (7/8 match) was associated with higher mortality (relative risk, 1.25; 95% CI, 1.13-1.38; P < .001) and 1-year survival of 43% compared with 52% for 8/8 matched pairs. Single mismatches at HLA-B or HLA-C appear better tolerated than mismatches at HLA-A or HLA-DRB1. Mismatching at 2 or more loci compounded the risk. Mismatching at HLA-DP or -DQ loci and donor factors other than HLA type were not associated with survival. In multivariate modeling, patient age, race, disease stage, and cytomegalovirus status were as predictive of survival as donor HLA matching. High-resolution DNA matching for HLA-A, -B, -C, and -DRB1 alleles is associated with higher rates of survival.

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