Selection of unrelated donors for allogeneic transplantation using post-transplant cyclophosphamide in acute lymphoblastic leukemia: An analysis by the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

There are conflicting data on the impact of mismatched unrelated donor (MMUD) compared to matched unrelated donor (MUD) in hematopoietic cell transplantation (HCT) with post-transplant cyclophosphamide (PTCy), highlighting the need for disease-specific research. We conducted a retrospective analysis of donor characteristics in 350 patients with acute lymphoblastic leukemia (ALL) in complete remission (CR) who received 8/8 human leukocyte antigen (HLA)-matched MUD and 7/8 HLA-matched MMUD. The primary endpoint was leukemia-free survival (LFS). The median age was 37 years (range, 18-76), with 231 (66%) in first CR, and 280 (80%) diagnosed with B-cell ALL. The median donor age was 28 years (range, 18-57), with 237 (68%) MUD and 113 (32%) MMUD. The use of MUD or MMUD did not have a significant impact on LFS or other transplant outcomes. Among other donor-related variables, cytomegalovirus (CMV)-negative donor for a CMV-negative recipient was associated with improved LFS (Hazard Ratio [HR] 0.55; 95% Confidence Interval [CI]: 0.32-0.96) and overall survival (HR 0.52; 95% CI: 0.28-1), while older donor age showed an increased risk of acute graft-versus-host disease (aGvHD) grade III-IV (HR 1.7; 95% CI: 1.1-2.64) and female donor to male recipient combination increased the risk of grade II-IV aGvHD (HR 1.78; 95% CI: 1.05-3). In conclusion, non-HLA donor characteristics rather than HLA matching should be prioritized to guide unrelated donor selection for ALL patients in the PTCy HCT setting.