Molecular measurable residual disease before transplantation independently predicts survival and relapse risk in adult lysine methyltransferase 2a‐rearranged acute myeloid leukemia

Abstract Background Patients with lysine methyltransferase 2a ( KMT2A )‐rearranged ( KMT2A ‐r) acute myeloid leukemia (AML) are assigned to intermediate‐risk and adverse‐risk categories at diagnosis. However, the value of molecular measurable residual disease (MRD) status in patients who have KMT2A ‐r AML before allogeneic hematopoietic stem cell transplantation (allo‐HSCT) in adult cohorts has rarely been evaluated. Methods Patients with KMT2A ‐r AML who achieved complete remission and subsequently underwent allo‐HSCT between January 2015 and January 2023 were included in this analysis. Real‐time quantitative polymerase chain reaction was used to detect molecular MRD in bone marrow samples. The end points were overall survival (OS), leukemia‐free survival (LFS), the cumulative incidence of relapse (CIR), and nonrelapse mortality (NRM). Results Pretransplantation molecular MRD was identified in 52 of 125 patients (42%) with KMT2A ‐r AML. The presence of KMT2A ‐r MRD was associated with inferior 3‐year OS (51% vs. 82%; p < .001), LFS (42% vs. 81%; p < .001), CIR (33% vs. 12%; p < .001), and NRM (11% vs. 5%; p = .12). In multivariate models, molecular MRD status before transplantation independently predicted OS, LFS, and CIR. The survival of adult patients with KMT2A ‐r AML was heterogeneous, depending on the KMT2A translocation partners, and was more favorable in patients who had t(9;11) and t(10;11) than in those who had t(11;19) and t(6;11). In addition, flow cytometry‐based MRD analysis conferred no additional prognostic value to the results of molecular MRD status. Conclusions Residual KMT2A ‐r before allo‐HSCT independently predicts the risk of survival and relapse, and donor lymphocyte infusion or posttransplantation maintenance therapies should be considered for patients who have AML with detectable molecular MRD.