The impact of HLA unidirectional mismatches on the outcome of myeloablative hematopoietic stem cell transplantation with unrelated donors.

The impact of HLA homozygosity at mismatched (MM) loci on the outcome of 2687 myeloablative unrelated donor hematopoietic cell transplantations performed for malignant disease was evaluated among 4 groups: 7/8 bidirectional MM transplants (donor and recipient heterozygous MM, n = 1393), 7/8 host-versus-graft (HVG) vector MM (recipient homozygous, n = 112), 7/8 graft-versus-host (GVH) vector MM (donor homozygous, n = 119), and 8/8 matches (n = 1063). Multivariate analyses found 7/8 GVH (P = .001) and bidirectional MM groups (P < .0001) had significantly worse transplant-related mortality and overall and disease-free survival than the 8/8 match group, a difference not observed with the 7/8 HVG MM group (P > .01). The 3 7/8 groups differed only for grades III-IV acute GVH disease (GVHD), where HVG MM had less GVHD than the 7/8 bidirectional MM (hazard ratio [HR] 0.52, P = .0016) and GVH MM (HR 0.43, P = .0009) groups but not the 8/8 group (HR 0.83, P = .39). There were no differences between the 7/8 groups for relapse, chronic GVHD, neutrophil engraftment, or graft failure. GVH MM have the same risk as 7/8 bidirectional MM. 7/8 HVG MM confer a reduced risk of acute GVHD without an increased risk of disease relapse or graft failure compared with a 7/8 bidirectional MM.