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.