Retrospective cohort study of mismatched unrelated versus matched related donor transplant with posttransplant cyclophosphamide for blood cancers

Relapse limits survival after allogeneic hematopoietic cell transplant. Although HLA-matched related donors (MRDs) are traditionally preferred, mismatched unrelated donors (MMUDs) using posttransplant cyclophosphamide (PTCy) may provide stronger graft-versus leukemia effects. A retrospective cohort study compared outcomes between MRD and MMUD transplant in the PTCy era and assessed whether MMUD grafts are associated with lower relapse rates. The MRD cohort was from MD Anderson Cancer Center (Houston, TX) and the MMUD cohort was from the Center for International Blood and Marrow Transplant Research. The study included 1038 patients with hematologic malignant tumors undergoing transplant from MRD (n=306) or MMUD (n=732) between 2017 and 2024. Among patients with a high or very high Disease Risk Index (DRI), MMUD transplant was associated with significantly lower relapse hazard versus MRD (weighted HR 0.56; p=0.03), althoug disease-free survival (DFS; HR 0.71; p=0.14) and overall survival (OS; HR 0.85; p=0.51) were similar. Conversely, in patients with low to intermediate DRIs, hazard estimates for DFS (HR 1.24’; p=0.16) and OS (HR 1.36; p=0.06) lacked precision. MMUD was associated with lower risk of grade III-IV acute GVHD (HR 0.56; p=0.04) but higher risk of chronic CVHD (HR 2.82; p<0.001). The authors conclude that in this cohort study, MMUD transplant was associated with lower relapse rate compared with MRD in patients with high-risk malignant tumors, potentially reflecting enhanced alloreactivity, although accompanied by increased chronic GVHD. MMUD grafts offered a distinct risk-benefit profile that warrants further investigation.