Correlation between disparity for the minor histocompatibility antigen HA-1 and the development of acute graft-versus-host disease after allogeneic marrow transplantation

Results of a previous study suggested that recipient mismatching for the mi nor histocompatibility antigen HA-1 is associated with acute graft-versus-h ost disease (GVHD) after allogeneic marrow transplantation. In that study, most patients received either cyclosporine or methotrexate for GVHD prophyl axis, and a cytotoxic T-cell clone was used to test for HA-1 disparity. To facilitate large-scale testing, we developed a method that uses genomic DNA to identify HA-1 alleles. A retrospective study was conducted to correlate HA-1 disparity and the occurrence of acute GVHD in 237 HLA-A2-positive whi te patients who had received a marrow or peripheral blood stem cell transpl ant from an HLA-identical sibling. All patients received both methotrexate and cyclosporine for GVHD prophylaxis. The presence of HLA-A*0201 was confi rmed in 34 of the 36 HA-1 disparate pairs by sequencing the HLA-A locus. Gr ades II-IV GVHD occurred in 22 (64.7%) of these 34 patients, compared with 86 (42.8%) of the 201 patients without HA-1 disparity (odds ratio, 2.45; 95 % confidence interval [CI], 1.15 to 5.23; P = .02). Recipient HA-1 disparit y showed a trend for association with acute GVHD (odds ratio, 2.1; 95% CI, 0.91 to 4.68; P = .08) when a multivariable logistic regression model was u sed to include additional risk factors. These data are consistent with resu lts of the previous study, suggesting an association between HA-1 disparity and risk of acute GVHD, but the strength of this association may be lower in patients who received both methotrexate and cyclosporine than in those w ho received methotrexate or cyclosporine alone. (C) 1999 by The American So ciety of Hematology.