Classification of HLA-matching for retrospective analysis of unrelated donor transplantation: revised definitions to predict survival.
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.
University of Minnesota, Minneapolis, Minnesota 55455, USA. weisd001@umn.edu
Daniel
D
Weisdorf
Stephen
S
Spellman
Michael
M
Haagenson
Mary
M
Horowitz
Stephanie
S
Lee
Claudio
C
Anasetti
Michelle
M
Setterholm
Rebecca
R
Drexler
Martin
M
Maiers
Roberta
R
King
Dennis
D
Confer
John
J
Klein
D000293:Adolescent; D000328:Adult; D003628:Database Management Systems; D018572:Disease-Free Survival; D005260:Female; D006680:HLA Antigens / Q000145:classification* / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006648:Histocompatibility; D006650:Histocompatibility Testing / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D014015:Tissue Banks; D014184:Transplantation, Homologous
D006680:HLA Antigens