How I Treat: Selection of Hematopoietic Cell Donors in the Era of Post-Transplant Cyclophosphamide

Selection of a hematopoietic progenitor cell donor for allogeneic hematopoietic cell transplantation (allo HCT) is essential for treatment planning; however, the parameters that define an "optimal" donor in the modern era are not well defined. Historically, donor-recipient human leukocyte antigen (HLA) mismatching correlated strongly with risk for graft versus host disease (GVHD) and reduced survival. For this reason, donor selection was typically hierarchical: HLA matched related and unrelated donors were evaluated first, followed by HLA mismatched donors (or deferral of HCT altogether) in patients lacking an HLA matched donor. The advent of post-transplant cyclophosphamide (PTCy)-based GVHD prevention has changed this paradigm. Survival outcomes following HLA-mismatched donor HCT with PTCy, including from related haploidentical or HLA-mismatched unrelated donors, are not different than HLA matched donor recipients in recent clinical trials and retrospective studies. These encouraging results present a new challenge: In the PTCy era, how should donors be prioritized among the many potential sources available? Herein we review HLA and non-HLA parameters that inform donor selection and discuss approaches to increase donor availability. Case vignettes focusing on concepts that may be adapted to heterogenous clinical scenarios are presented.