Hematologic tumors are increasingly being treated with hematopoietic cell transplantation from HLA-haploidentical related donors; nevertheless, the qualities of the ideal haploidentical donor have yet to be determined. For 1,434 acute leukemia or myelodysplastic syndrome patients reported to the Center for International Blood and Marrow Transplant Research, researchers investigated the role of donor HLA mismatching in graft-versus-host disease (GVHD), disease recurrence, and survival after haploidentical donor transplantation with posttransplantation cyclophosphamide (PTCy). 

Using multivariable regression approaches, the impact of mismatching in the graft-versus-host vector for the HLA-A, -B, -C, -DRB1, and -DQB1 alleles, the HLA-B leader, and the HLA-DPB1 T-cell epitope (TCE) was investigated. The HLA mismatches at individual loci were linked to the outcome rather than the total number of HLA mismatches. In addition, mismatches in the HLA-DRB1 gene were linked to a decreased likelihood of illness recurrence. 

Mismatching HLA-DRB1 with HLA-DQB1 was linked to a long, disease-free life. Overall survival was related to HLA-B leader matching and HLA-DPB1 TCE-nonpermissive mismatching. HLA-C matching reduced the incidence of persistent GVHD, and HLA-C expression was linked to transplant-related death. Patient and donor CMV serostatus, patient age, and comorbidity index all predicted disease-free survival, as did matching status at the HLA-B leader and HLA-DRB1, -DQB1, and -DPB1. By estimating disease-free survival based on these features, a web-based tool was built to aid in the selection of the best haploidentical-related donor. 

Finally, HLA variables had a role in the effectiveness of PTCy-based haploidentical transplantation. Mismatching of HLA-DRB1 and -DPB1 and HLA-C, -B leader, and -DQB1 matching were both beneficial. The use of HLA variables in selecting haploidentical related donors might be beneficial.