Integrating cytogenetic profiling, MRD dynamics, and HSCT outcomes in adult Ph-negative B-ALL

Results from a single-center retrospective study, evaluating the impact of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on cytogenetics, measurable residual disease (MRD), and survival in 368 patients with Philadelphia chromosome-negative (Ph−) B-cell acute lymphoblastic leukemia (B-ALL), were published in Clinical Lymphoma, Myeloma and Leukemia by Liu et al. Key outcomes included disease-free survival (DFS) and overall survival (OS).

Key data: Overall, 48.1% of patients had cytogenetic abnormalities. Among patients who underwent allo-HSCT, the 5-year OS and DFS rates were 58.8% and 42.0%, respectively; rates did not differ between patients with and without cytogenetic abnormalities in the HSCT group. Among patients who did not undergo allo-HSCT, those with KMT2A-rearrangement (KMT2A-r) (DFS, p = 0.021; OS, p = 0.036), 14q32/IGH (DFS, p = 0.004; OS, p = 0.047), and t(1;19) (DFS, p < 0.001; OS, p < 0.001) had significantly worse DFS and OS vs those without cytogenetic abnormalities. Post-consolidation MRD positivity independently predicted DFS impairment in non-transplant patients (p = 0.012), while reduced-intensity conditioning (RIC) was the only independent risk factor for DFS in allo-HSCT recipients (p = 0.011). 

Key learning: Results suggest that allo-HSCT mitigates the adverse prognosis of high-risk cytogenetic abnormalities in adult Ph− B-ALL, supporting a dual approach of allo-HSCT for high-risk or MRD-positive patients and MRD-guided therapy for transplant-ineligible patients.