Donor selection for allogeneic hematopoietic cell transplantation in the posttransplant cyclophosphamide era

The adoption of posttransplant cyclophosphamide (PTCy) as graft-versus-host disease prophylaxis has reduced non-relapse mortality in allogeneic hematopoietic cell transplantation (allo-HCT) by overcoming the barrier of HLA disparity. Allo-HCT from an HLA-haploidentical-related donor with PTCy (PTCy-haplo) has become a feasible allo-HCT platform. Even in the PTCy era, allo-HCT from an HLA-matched related donor (MRD) has achieved the highest overall survival. However, the optimal donor choice when an MRD is unavailable remains a subject of debate. We discuss outcomes of PTCy-haplo compared with alternative donor sources, such as HLA-matched unrelated donors, HLA-mismatched unrelated donors, and cord blood, and propose a provisional donor selection matrix that combines HLA matching with clinical urgency. In clinical practice, even when multiple donor candidates are available, it is rare to find one with all favorable prognostic factors, including donor age, CD34⁺ cell dose, HLA-related factors, anti-HLA antibodies, donor sex, cytomegalovirus serostatus, and donor coordination period. Therefore, it is crucial to select the most suitable donor for each case rather than aiming for a perfect match. Further efforts should focus not only on identifying new prognostic factors but also on developing improved donor selection algorithms that account for the hierarchy among factors and integrate them effectively.