Pre-transplant immunotherapy and MRD dynamics affect post-transplant prognosis in KMT2A-rearranged B-ALL patients

To explore factors affecting post-transplant outcomes in patients with KMT2A-rearranged (KMT2A-r) B-cell acute lymphoblastic leukemia (B-ALL), we performed a retrospective study including 44 newly diagnosed KMT2A-r B-ALL patients treated at the First Affiliated Hospital of Soochow University from 2018 to 2025. KMT2A-r and MFC-MRD were assessed at four time points: post-induction (MRD1), post-first consolidation (MRD2), post-second consolidation (MRD3), and pre-transplant (MRD4). Incorporation of immunotherapy (CAR-T or blinatumomab) into induction and consolidation regimens enhanced remission depth at all MRD1 to MRD4 time points. Immunotherapy bridging to transplantation was associated with superior overall survival (OS) compared with direct transplantation (P = 0.03), with a trend toward longer median relapse-free survival (RFS) of 39.0 (95% CI: 3.9-74.1) vs. 5.0 (95% CI: 1.6-8.4) months (P = 0.10). In addition, the cumulative incidence of relapse (CIR) was lower in the immunotherapy bridging to transplantation group (P = 0.02). KMT2A-r and MFC-MRD negativity peaked pre-transplant. Four dynamic patterns were identified; sustained or converted negativity correlated with better prognosis, and sustained positivity with poor outcomes. Multivariate analysis revealed that sustained KMT2A positivity and the absence of pre-transplant immunotherapy were independent adverse risk factors. In conclusion, first-line immunotherapy yields deeper remission; immunotherapy bridging to transplantation is superior; dynamic KMT2A-r and MFC-MRD strongly predict post-transplant prognosis.