SOHO State of the Art Updates and Next Questions | Current Status and Future Directions of Donor Selection

The landscape of HLA matching in hematopoietic cell transplantation (HCT) is continuously advancing, introducing more nuanced criteria beyond traditional 10/10 HLA-A, -B, -C, and -DRB1 allele matching. For 10/10 matched donors, prioritizing a donor with a "core" permissive HLA-DPB1 mismatch is recommended over "noncore" permissive mismatches, with nonpermissive mismatches being the least prefered. In the one-antigen mismatched setting (7/8 HLA-matched), HLA-C matching, particularly avoiding high-expression mismatches at residues 116 or 77/80, is preferred over HLA-A or HLA-B mismatches. HLA B-leader matching is beneficial in both one-antigen mismatched and haploidentical HCT. Additionally, specific HLA mismatches in haploidentical HCT, such as DRB1 mismatches with DQB1 matches and DPB1 nonpermissive mismatches are linked to better outcomes. Among non-HLA factors, evidence consistently underscores the pivotal impact of donor age on overall survival. For HLA-mismatched transplants, including haploidentical HCT, avoidance of donors against whom the recipient has preformed donor-specific antibodies is paramount. Selecting a cytomegalovirus (CMV) seronegative donor is important particularly for CMV-negative recipients; however, more research is needed in the letermovir prophylaxis era. The impact of ABO-matching on transplant outcomes is debatable. Other unanswered questions include defining "younger" donors and establishing hierarchy in donor selection based on factors like CMV status, ABO compatibility, or sex-mismatch, to name a few. Future research addressing these issues will refine donor selection algorithms and improve transplant success. In conclusion, selecting a donor for HCT requires multifaceted considerations, integrating evolving HLA-matching criteria and non-HLA factors, to optimize HCT outcomes in this rapidly advancing field.