The impact of T-cell depletion on the effects of HLA DRβ1 and DQβ allele matching in HLA serologically identical unrelated donor bone marrow transplantation

Unrelated donor bone marrow transplants have been associated with relatively high rates of acute graft-vs.-host disease and treatment-related mortality. These complications reflect histo-incompatibility between donor and recipient. Molecular technology has recently been applied to HLA typing to identify alleles not distinguishable with serologic typing techniques. We report results in 92 unrelated marrow transplant recipients who were HLA seroidentical with donor HLA-A, -B, and -DR antigens and assess the effect of DRβ1 and DQβ compatibility using sequence specific oligonucleotide primers. Forty-eight patients received T-cell depleted marrow grafts, and 44 received unmodified grafts. Among recipients of unmodified marrow grafts, matching for both DRβ1 and DQβ reduced the rate of grade 3-4 acute graft-vs.-host disease to 38 ± 20% vs. 73 * 20% among recipients mismatched for either allele (p = 0.02). This difference was not observed in recipients of T-cell depleted marrow grafts. Multivariate analysis confirmed matching for both DRβ1 and DQβ loci (p = 0.015), and receiving a T-cell depleted graft (p = 0.008) independently predicted for reduced risk of grade 3-4 acute graft-vs.-host disease. In conclusion, both DRβ1 and DQβ appear biologically important for development of acute graft-vs.-host disease in patients receiving unmanipulated marrow grafts for unrelated donor transplant.