Optimal Donor Selection for Allogeneic Stem Cell Transplantation in the Era of Post-transplant Cyclophosphamide: A Scoping Review

Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) remains a primary curative treatment for numerous hematologic disorders. Historically, the success of HSCT relied on HLA matching to mitigate Graft-versus-Host Disease (GVHD); however, since fewer than 30% of patients have a matched family member, the field has undergone a significant paradigm shift. The emergence of haploidentical HSCT, facilitated by the post-transplantation cyclophosphamide (PTCy) GVHD prophylaxis platform, has revolutionized donor availability, resulting in clinical outcomes for mismatched transplants that are comparable to those of matched sibling or unrelated donors. Beyond HLA compatibility, several non-HLA factors are now critical in donor selection. Younger donor age has emerged as a remarkable predictor of survival, reducing both relapse and non-relapse mortality; nevertheless, HLA matching and disease biology remain major drivers. Furthermore, considerations such as Cytomegalovirus (CMV) serostatus, the presence of donor-specific antibodies (DSA), and the urgency of the procedure—prioritizing time-to-transplant over a perfect HLA match—are essential. Ultimately, while histocompatibility remains a priority, modern HSCT leverages PTCy to balance biological compatibility with clinical speed, significantly expanding the curative potential for patients worldwide.