Impact of Measurable Residual Disease Status on Outcomes After HLA-Matched Donor Allogeneic Hematopoietic Cell Transplantation in Acute Myeloid Leukemia.
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BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HCT) is a key treatment for acute myeloid leukemia (AML). Measurable residual disease (MRD) predicts post-transplant outcomes. This study evaluates the impact of pretransplant MRD status on outcomes in AML patients undergoing allo-HCT. METHODS: We retrospectively analyzed AML patients who underwent allo-HCT from matched related or unrelated donors (2013-2018) using the CIBMTR P-5646 dataset. Patients were stratified by pretransplant MRD status. Outcomes included overall survival (OS), disease-free survival (DFS), relapse, nonrelapse mortality (NRM), acute graft-versus-host disease (aGVHD), GVHD-free relapse-free survival (GRFS), and engraftment. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated using multivariate Cox regression, adjusted for significant univariate variables (P < .05). RESULTS: Of 2404 AML patients (354 MRD-positive, 2050 MRD-negative), MRD-positive patients had a lower Karnofsky performance status (≥90%: 46.1% vs. 55.1%, P = .004) and were more likely to undergo myeloablative conditioning (66.6% vs. 52.7%, P < .001). MRD positivity predicted worse OS (HR 1.91, 95% CI 1.62-2.23, P < .001), DFS (HR 2.05, 95% CI 1.77-2.36, P < .001), relapse (HR 2.25, 95% CI 1.91-2.64, P < .001), aGVHD grade II to IV (HR 1.24, 95% CI 1.03-1.50, P = .024), GRFS (HR 1.59, 95% CI 1.41-1.81, P < .001), and slower platelet engraftment (HR 0.71, 95% CI 0.63-0.81, P < .001). NRM (P = .387) and neutrophil engraftment (P = .159) were similar. CONCLUSION: Pretransplant MRD status predicts post-allo-HCT outcomes, with MRD positivity associated with reduced overall and disease-free survival and increased relapse risk. Personalized MRD-directed strategies are needed to optimize outcomes in AML patients undergoing allogeneic transplantation.