Precision in donor selection: Identifying ideal stem-cell donors through their T cells

HLA-identical siblings have always been considered ideal donors for allogeneic hematopoietic stem-cell transplantation (allo-HSCT) in the treatment of hematologic cancers. Recent data suggest that we should rethink this paradigm. In "High Graft CD8+ Cell Dose Predicts Improved Survival and Enables Better Donor Selection in Allogeneic Stem-Cell Transplantation With Reduced-Intensity Conditioning," we identified a group of stem-cell donors whose grafts contain an optimal composition of T-cells, leading to a dramatic decrease in disease relapse risk and an improvement in overall survival following allo-HSCT. To demonstrate this, we analyzed the outcomes of 200 patients with hematologic malignancies who underwent allo-HSCT after reduced-intensity conditioning (RIC). The analysis focused on T-cell content of peripheral blood stem-cell grafts. We found that higher graft CD8+ T-cell dose (CD8hi), a trait found only in grafts collected from young donors, was associated with improved survival due to a reduction in the risk for cancer relapse without a significant increase in graft-versus-host disease (GVHD). Though not all young donors mobilized CD8hi grafts, we found that a low CD4:CD8 ratio in the peripheral blood could identify these ideal donors prior to transplant. The likelihood of finding CD8hi donors correlated inversely with age, and elderly RIC transplant recipients had a low chance of receiving an ideal graft from their similarly aged siblings. Here, we examine these findings and their implications on choosing donors according to age and relatedness. We also explore biological mechanisms that determine the CD4:CD8 ratio in healthy donors.