HLA and Non-HLA Factors for Donor Selection in Hematopoietic Stem Cell Transplantation with Post-Transplant Cyclophosphamide GvHD Prophylaxis

Human leukocyte antigen (HLA) mismatches in stem cell transplantation can be well-tolerated with the use of post-transplant cyclophosphamide (PTCy) for graft-versus-host-disease (GvHD) prophylaxis. Haploidentical (Haplo) and HLA-mismatched unrelated donors become acceptable donors. This review focuses on Haplo and unrelated donor selection in the context of PTCy-transplant for hematological malignancy, in comparison with conventional GvHD prophylaxis. Evaluating patient’s donor-specific antibody (DSA) is critical in donor selection regardless of donor type or the use of PTCy. High DSA levels and positive C1q increase the risk of engraftment failure and unsuccessful desensitization. On the other hand, the degree of donor HLA matching is less critical under PTCy compared to conventional GvHD prophylaxis. Donor age was found to be important, as younger donors improve survival outcomes. HLA-B leader match appears to be preferable. The impacts of donor gender, donor cytomegalovirus serostatus, and ABO mismatch are unclear or non-significant. Additionally, available studies suggest that, in PTCy-transplant, preferred Haplo-donors are HLA class II mismatched (DRB1 mismatch and DPB1 non-permissive), siblings or offspring over parents, and if parent, father over mother, while preferred unrelated donors are HLA class I matched. Further study is warranted.