Among patients with high-risk hematologic malignancies who underwent hematopoietic cell transplantation with posttransplant cyclophosphamide, mismatched unrelated donor (MMUD) transplantation was associated with lower relapse rates than matched related donor (MRD) transplantation while showing comparable disease-free and overall survival, according to a retrospective cohort study by Mehta et al published in JAMA Network Open. The relapse benefit was accompanied by a higher risk of chronic graft-vs-host disease (GVHD).
“For patients with aggressive disease, MMUD grafts may offer enhanced relapse protection, suggesting donor selection should align with disease risk rather than relying solely on historical hierarchies,” the investigators commented.
Study Details
The investigators focused on patients with acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome and/or myeloproliferative neoplasm who underwent their first peripheral blood hematopoietic cell transplant with posttransplant cyclophosphamide.
The MRD cohort included 306 consecutive patients who underwent transplantation at The University of Texas MD Anderson Cancer Center between January 1, 2017, and August 31, 2024. The MMUD cohort included 732 patients identified from a publicly available, deidentified Center for International Blood and Marrow Transplant Research data set who underwent transplantation between January 1, 2017, and December 31, 2021.
The main outcomes were disease-free survival, overall survival, relapse, nonrelapse mortality, and GVHD. To address structural confounding, particularly donor age, the investigators used inverse probability of treatment weighting with overlap weights and bootstrapping. They compared outcomes between the groups using Cox proportional hazards models.
Key Findings
Among patients with a high or very high Disease Risk Index (DRI), the 3-year cumulative incidences of relapse were 39.2% vs 58.6% with MMUD vs MRD transplantation, respectively (P = .004). Consistent with this difference, MMUD transplantation was found to be associated with a lower hazard of relapse than MRD transplantation (weighted hazard ratio [HR] = 0.56, 95% confidence interval [CI] = 0.33–0.94; P = .03), although disease-free (HR = 0.71, 95% CI = 0.46–1.11; P = .14) and overall (HR = 0.85, 95% CI = 0.53–1.37; P = .51) survival did not appear to differ significantly between the groups.
The investigators noted that the hazard estimates for disease-free (HR = 1.24, 95% CI = 0.92–1.66; P = .16) and overall (HR = 1.36, 95% CI = 0.99–1.88; P = .06) survival lacked precision among those with low to intermediate DRI scores.
MMUD transplantation seemed to be associated with a lower risk of grade III or IV acute GVHD (HR = 0.56, 95% CI = 0.32–0.98; P = .04) but an increased risk of chronic GVHD (HR = 2.82, 95% CI = 2.02–3.95; P < .001).
The investigators concluded, “In this cohort study…, the most consistent and clinically relevant signal that emerged was the reduction in relapse with MMUD HCT [hematopoietic cell transplant] compared with MRD HCT among patients with high- or very high–risk disease. Across analytic approaches, there was no indication that the MMUD group performed worse than the MRD group in this subgroup. Taken together, these data support the view that MMUD grafts may offer a biologically meaningful advantage for patients with aggressive disease.”
Looking ahead, they stated, “Validation in larger, independently assembled cohorts will be essential to determine whether this enhanced disease control ultimately translates into durable survival benefit.”
Rohtesh S. Mehta, MD, MPH, MS, of The University of Texas MD Anderson Cancer Center, Houston, is the corresponding author of the article in JAMA Network Open.
DISCLOSURE: For full disclosures of the study authors, visit jamanetwork.com. Part of the data set used in this study (the MMUD cohort) was provided by the Center for International Blood and Marrow Transplant Research, which is supported primarily by the U.S. Public Health Service; a grant from the National Cancer Institute; the National Heart, Lung, and Blood Institute; the National Institute of Allergy and Infectious Diseases; a grant from the Health Resources and Services Administration; grants from the Office of Naval Research; the National Marrow Donor Program; and the Medical College of Wisconsin.
