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

Unrelated donor (URD) hematopoietic cell transplantation (HCT) is best performed using a donor who is allele-matched with the recipient at HLA-A,B,C and DR. Earlier reports analyzing outcomes of HCT have been limited by incomplete or lower resolution typing at some HLA loci. Excluding these incompletely typed pairs from studies decreases the power of analyses because of smaller sample size. If adjustment for known and unknown HLA-matching status could be accomplished, these patients could be retained in most analyses where HLA-matching is not the primary research focus. To understand the impact of incompletely characterized major histocompatibility antigens on the success of HCT, we analyzed 15,867 URD HCT using multivariable regression modeling adjusting for HLA and non-HLA factors affecting 1 year and 5 year survival. Of 26 independent matching groups defined by the completeness and resolution of donor:recipient pair matching we identified 3 distinct groups with significantly different outcomes: well matched, partially matched, and mismatched. Well-matched cases had no identified HLA mismatch and informative, though not necessary high-resolution data at all 4 loci or allele matching at HLA-A,B & DRB1 (n=7,753, 49% of the study population). Partially matched pairs had a defined, single locus mismatch at any of the 4 loci and/or missing HLA-C data [including 6/6 low/intermediate resolution A,B matched plus DRB1 allele matched] (n=5,396, 34%). Mismatched cases had 2 or more identified allele or antigen mismatches (n=2,692, 17%). Multiple-variable-adjusted one- and five-year survival estimates are shown in the Table. Using these HLA matching categories, we identified independently significant, 7–8% better 5 year survival using a better matched donor (between these 3 categories) stratified across patient subgroups of recipient age, disease stage, and using either myeloablative or non-ablative conditioning. Notably, the common term “6/6 antigen matched” [6/6 low/intermediate resolution A,B matched plus DRB1 allele matched] had survival outcomes within the partial matched cohort. We suggest that these HLA subgroups should be used in analyses of URD HCT outcomes when complete HLA typing is not available. This improved categorization of HLA matching status allows adequate adjustment for HLA donor-recipient HLA compatibility in retrospective studies and will help standardize interpretations of prior URD HCT experience.