Classification of HLA-Matching for Retrospective Analysis of Unrelated Donor Transplantation: Revised Definitions to Predict Survival

University of Minnesota, Minneapolis, Minnesota 55455, USA.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation (Impact Factor: 3.4). 08/2008; 14(7):748-58. DOI: 10.1016/j.bbmt.2008.04.003
Source: PubMed


The best unrelated donors (URD) for hematopoietic cell transplantation (HCT) are alleles matched at HLA-A, -B, -C, and DRB1. Earlier studies mostly used incomplete or lower resolution HLA typing for analysis of transplant outcome. To understand the impact of incomplete HLA characterization, we analyzed 14,797 URD HCT (1995-2006) using multivariable regression modeling adjusting for factors affecting survival. Of 21 matching cohorts, we identified 3 groups with significantly different outcomes. Well-matched cases had either no identified HLA mismatch and informative data at 4 loci or allele matching at HLA-A, -B, and -DRB1 (n = 7477, 50% of the population). Partially matched pairs had a defined, single-locus mismatch and/or missing HLA data (n = 4962, 34%). Mismatched cases had > or =2 allele or antigen mismatches (n = 2358, 16%). Multivariate adjusted 5-year survival estimates were: well-matched: 54.1 (95% confidence interval), 52.9-55.4), partially matched: 43.7 (42.3-45.2), and mismatched: 33.4 (32.5-36.5), P < .001. A better matched donor yielded 10%-11% better 5-year survival. Importantly, intermediate resolution -A, -B, and -DRB1 alleles matched "6/6 antigen matched" HCT had survival outcomes within the partially matched cohort. We suggest that these proposed HLA subgroupings be used when complete HLA typing is not available. This improved categorization of HLA matching status allows adjustment for donor-recipient HLA compatibility, and can standardize interpretations of prior URD HCT experience.

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    • "Graft sources included HLA identical sibling bone marrow (BM) or peripheral blood stem cells (PBSC; n = 315), HLA mismatched sibling or related donor BM or PBSC, (n = 24), well matched (Weisdorf, et al 2008) URD BM or PBSC (n = 79), partially matched URD BM or PBSC (n = 108), mismatched URD BM or PBSC (n=126), single unit (n = 89) or double UCB (n=123). "
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    • "The definitions of human leucocyte antigen (HLA)-matching for the unrelated donor transplants shown to have correlation with survival was adopted and included in the prognostic models when applicable.(Weisdorf, et al 2007) The well-matched pairs had no identified HLA mismatch and informative though not necessarily high resolution in all 4 loci (HLA-A, HLA-B, HLA-C and HLA-DRB1) (N=80); partially matched pairs had a defined single locus mismatch at any of the 4 loci and/or missing HLA-C data (N=18) and mismatched pairs had 2 or more identified allele or antigen mismatches (N=7). "
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