Nonmyeloablative HLA-haploidentical bone marrow transplantation with high-dose posttransplantation cyclophosphamide: effect of HLA disparity on outcome

Abstract

Although some reports have found an association between increasing HLA disparity between donor and recipient and fewer relapses after allogeneic blood or marrow transplantation (BMT), this potential benefit has been offset by more graft-versus-host disease (GVHD) and nonrelapse mortality (NRM). However, the type of GVHD prophylaxis might influence the balance between GVHD toxicity and relapse. The present study analyzed the impact of greater HLA disparity on outcomes of a specific platform for nonmyeloablative (NMA), HLA-haploidentical transplantation. A retrospective analysis was performed of 185 patients with hematologic malignancies enrolled in 3 similar trials of NMA, related donor, haploidentical BMT incorporating high-dose posttransplantation cyclophosphamide for GVHD prophylaxis. No significant association was found between the number of HLA mismatches (HLA-A, -B, -Cw, and -DRB1 combined) and risk of acute grade II-IV GVHD (hazard ratio [HR] = 0.89; P = .68 for 3-4 vs fewer antigen mismatches). More mismatching also had no detrimental effect on event-free survival (on multivariate analysis, HR = 0.60, P = .03 for 3-4 vs fewer antigen mismatches and HR = 0.55, P = .03 for 3-4 vs fewer allele mismatches). Thus, greater HLA disparity does not appear to worsen overall outcome after NMA haploidentical BMT with high-dose posttransplantation cyclophosphamide.

Figure 1

Outcomes according to donor-recipient HLA mismatching. A, Event-free survival and B, cumulative incidences of relapse and nonrelapse mortality according to the number of antigen mismatches in either direction. C, Cumulative incidence of acute grade II–IV GVHD according to the number of antigen mismatches in the GVH direction. Cumulative incidences were estimated by competing risk analysis. Analyses are based upon the number of mismatches at HLA-A, -B, -Cw, and -DRB1 combined. Ag, antigen; MM, mismatch; NRM, nonrelapse mortality.