THE SIGNIFICANCE OF HLA-DRB1 MATCHING ON CLINICAL OUTCOME AFTER HLA-A, HLA-B, HLA-DR IDENTICAL UNRELATED DONOR MARROW TRANSPLANTATION

Despite matching for serologically defined HLA-A, B, DR antigens, acut e graft-versus-host disease (GVHD) is a major complication contributin g to increased morbidity and mortality in patients who undergo marrow transplantation from unrelated donors. The extent to which unrecognize d mismatching for alleles that encode DR1-DR18 contribute to the incre ased risk of acute GVHD and overall survival is unknown, We analyzed 3 64 patients and their HLA-A, B, DR serologically matched donors to det ermine whether molecular typing of DRB1 alleles can allow more accurat e donor/ recipient matching and thereby improve clinical outcome after marrow transplantation. DRB1 alleles were typed by sequence-specific oligonudeotide probe hybridization methods, Selected alleles were conf irmed by DNA sequencing. Of the 364 pairs, 305 were matched and 59 wer e mismatched for DRB1. The probability of moderate to severe acute GVH D was .48 for the matched and .70 for the mismatched patients, Compare d with mismatched patients, the estimated relative risk (RR) of GVHD f or matched patients was .58 (95% confidence interval [Cl](r) .40 to .8 5), DRB1 matching decreased the risk of transplant-related mortality ( RR, .66; 95% Cl, .44 to .97) end was associated with decreased overall mortality (RR, .71; 95% Cl, .51 to 1.0). Therefore, matching DRB1 all eles of the donor and recipient decreases the risk of acute GVHD and i mproves survival after unrelated marrow transplantation. These results indicate that prospective matching of patients and donors for DRB1 al leles is warranted. (C) 1995 by The American Society of Hematology.