Donor selection in PTCy haploidentical transplant for acute lymphoblastic leukemia: a study from the ALWP of the EBMT

Haploidentical hematopoietic cell transplantation (HCT) is widely used in high-risk acute lymphoblastic leukemia (ALL), yet optimal donor selection remains unclear. We retrospectively analyzed 933 ALL patients receiving post-transplant cyclophosphamide (PTCy)-based GVHD prophylaxis to evaluate the impact of donor characteristics on outcomes. Donors had a median age of 36 years; 38% were female, including 23% who donated to male recipients. Peripheral blood (PB) was the graft source in 69%, and CMV-seronegative donors were used in 16% of CMV-negative recipients. Multivariate analysis showed that PB grafts were associated with inferior overall survival (OS) and GVHD-free/relapse-free survival. CMV-matched seronegative pairs had reduced non-relapse mortality and improved OS. Chronic GVHD was more frequent with older donors and in male recipients of female donor grafts, the latter also increasing extensive cGVHD risk. In conclusion, donor and graft selection significantly influence outcomes after haplo-HCT with PTCy. When feasible, bone marrow should be favored over PB grafts, and CMV-seronegative donors prioritized for CMV-seronegative recipients. Older donor age and female-to-male sex mismatch were associated with increased chronic GVHD risk.