Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation in Adult Patients with Acute Myeloid Leukemia Harboring KMT2A Rearrangement and Its Prognostic Factors

Background:KMT2A rearrangement ( KMT2A-r) in patients with acute myeloid leukemia (AML) is associated with poor outcomes; the prognostic factors after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear.

Methods: We investigated 364 adults with AML who underwent allo-HSCT between April 2016 and May 2022, and 45 had KMT2A-r among them. Propensity score analysis with 1:1 matching and the nearest neighbor matching method identified 42 patients in KMT2A-r and non- KMT2A-r cohorts respectively.

Results: The 2-year overall survival (OS), relapse-free survival (RFS), cumulative incidence of relapse (CIR), and non-relapsed mortality (NRM) rates of patients with KMT2A-r were 59.1%, 49.6%, 41.5%, and 8.9%, respectively. With propensity score matching, the 2-year OS rate of KMT2A-r patients was lower than in those without KMT2A-r (56.1% vs. 88.1%, P=0.003), and in patients who achieved first complete remission (CR1), flow cytometry-based measurable residual disease (FCM-MRD) <1% and KMT2A-r negative before HSCT, the difference in the 2-year OS rate was reduced (71.5% vs. 93.9%, P=0.065). Patients with KMT2A-r exhibited the prognostic advantage from transplantation while in CR1 with FCM-MRD <1% and KMT2A-r negative which was reflected in OS, RFS, and CIR ( P<0.001, P<0.001, P=0.002, respectively). Besides, there were differences in OS, RFS, and CIR depending on KMT2A-r subtypes ( P=0.032, P=0.001, P=0.001, respectively). However, there was no difference regardless of the presence of mutations (all P>0.05). Univariate and multivariate analyses demonstrated that achieving CR1, FCM-MRD <1% and KMT2A-r negative before HSCT was a protective factor for OS (HR=0.242, P=0.007), RFS (HR=0.350, P=0.036), and CIR (HR=0.271, P=0.021), while AF6 was a risk factor for RFS (HR=2.985, P=0.028) and CIR (HR=4.675, P=0.004).

Conclusion: The poor prognosis of patients with KMT2A-r AML is associated with KMT2A-r subtypes, but not the presence of mutations. These patients can benefit from achieving CR1, FCM-MRD <1% and KMT2A-r negative before HSCT.