Haploidentical
hematopoietic stem cell transplantation (haplo-HSCT) with unmanipulated grafts is increasingly adopted for high-risk acute
leukemia, with acute
graft-versus-host disease (aGVHD) prophylaxis based on
antithymocyte globulin (ATG) or posttransplant
cyclophosphamide (PTCy) as main platforms. No consensus exists on selection criteria over several haploidentical donors. We evaluated the impact of donor-recipient antigenic and allelic
HLA-A, -B, -C, and -DRB1 mismatches on mismatched haplotype on outcomes of 509 unmanipulated haplo-HSCTs performed for acute
leukemia under a PTCy (N = 313) or ATG (N = 196) regimen. An antigenic but not allelic mismatch at the
HLA-DRB1 locus was an independent risk factor for grade ≥2 aGVHD in PTCy (hazard ratio [HR], 2.0; 95% confidence interval [CI], 1.2-4.0; P = .02) but not in ATG regimens (HR, 1.3; 95% CI, 0.4-3.4; P = .6). Moreover, the hazards of aGVHD were significantly associated with other factors influencing alloreactivity, including peripheral blood as stem cell source (HR, 2.2; 95% CI, 1.4-3; P < .01), reduced-intensity conditioning (HR, 0.6; 95% CI, 0.4-0.9; P = .04), and female donors (HR, 1.8; 95% CI, 1-3.2; P = .05), in PTCy but not ATG regimens. No significant associations were found between cumulative number of HLA mismatches and GVHD, or between HLA-matching status and other study end points including transplant-related mortality, disease-free survival, and relapse. Based on these data, the role of HLA mismatching on unshared haplotype appears not to be sufficiently prominent to justify its consideration in haploidentical
donor selection. However, the role of HLA matching in haploidentical HSCT might be modulated by GVHD prophylaxis, calling for further investigations in this increasingly relevant field.