EFFECT OF MATCHING OF CLASS-I HLA ALLELES ON CLINICAL OUTCOME AFTER TRANSPLANTATION OF HEMATOPOIETIC STEM-CELLS FROM AN UNRELATED DONOR

Background The requirements with respect to HLA compatibility and the relative importance of matching for individual class I and class II HL A alleles in the transplantation of hematopoietic stem cells from unre lated donors have not yet been established. Methods We performed retro spective DNA typing of alleles at 11 polymorphic loci of HLA genes in 440 recipients of hematopoietic stem cells from unrelated donors who w ere serologically identical with their respective recipients for HLA-A , B, and DR antigens. Of these recipients, 80 percent had leukemia; th e rest had lymphoma, marrow failure, or a congenital disorder. Results Multivariate analysis showed that incompatibility for HLA-A alleles a nd incompatibility for HLA-C alleles were independent risk factors for severe acute graft-versus-host disease (GVHD) (HLA-A, P=0.006; HLA-C, P=0.001). Mismatching of HLA-A, but not of HLA-C, alleles was an inde pendent risk factor for death (P<0.001). Mismatching of HLA-C alleles was a significant risk factor for relapse of leukemia (P=0.035). HLA-B disparity was a significant risk factor for both GVHD and death in th e univariate analysis, but not in the multivariate analysis. Dispariti es in class II HLA alleles of the DRB1, DQA1, DQB1, DPA1, and DPB1 loc i were not identified as significant risk factors for acute GVHD or de ath in the multivariate analysis. Conclusions Genomic typing of class I HLA alleles adds substantially to the success of transplantation of hematopoietic stem cells from unrelated donors, even if the donors are serologically identical to their recipients with respect to HLA-A, B, and DR antigens. (N Engl J Med 1998;339:1177-85.) (C) 1998, Massachus etts Medical Society.