Allogeneic transplantation for AML with RUNX1::RUNX1T1 fusion: a time-dependent analysis in a retrospective study

Abstract

The prognostic significance of measurable residual disease (MRD) in guiding allogeneic hematopoietic cell transplantation (Allo-HCT) in acute myeloid leukemia (AML) with RUNX1::RUNX1T1 fusion in first complete remission (CR1) requires further elucidation. This retrospective study analyzed 246 patients diagnosed AML with RUNX1::RUNX1T1 fusion to evaluate the prognostic impact of MRD following the second consolidation therapy and the effectiveness of Allo-HCT after achieving CR1. Our findings indicated that 64/246 patients (26%) had a MRD reduction less than 3-log post-second consolidation therapy and it is an independent adverse factor for both CIR (HR = 6.93, P < 0.001) and OS (HR = 6.97, P < 0.001). Then the impact of Allo-HCT in CR1 on outcome was analyzed by univariate, multivariate time-dependent model and multistate model. Results suggested Allo-HCT in CR1 was significantly associated with better DFS and OS (DFS: HR = 0.21, P < 0.001; OS: HR = 0.27, P = 0.002) for patients with MRD reduction less than 3-log in univariate time-dependent analyses and was an favorable factor for survival in multivariate model adjusted for MRD and KIT mutation (DFS: HR = 0.21, P < 0.001; OS:HR = 0.31, P = 0.002) without increasing NRM (HR = 0.85, P = 0.75). In multistate model, the 5-year predicted probability of remaining in CR without undergoing Allo-HCT is significantly lower for patients with MRD reduction less than 3-log compared with those achieved MRD reduction ≥ 3-log (5.2% vs. 50.0%). These findings support MRD-directed Allo-HCT to exert a substantial influence on outcomes for AML patients with RUNX1::RUNX1T1 fusion. These results advocate for the incorporation of MRD status in the criteria for transplantation eligibility to enhance survival rates.