Peri-transplant molecular MRD monitoring by targeted NGS in patients with FLT3-ITD mutated acute myeloid leukemia

Relapse is the predominant cause of treatment failure after allogeneic hematopoietic cell transplantation (allo-HCT) in FLT3-ITD-mutated AML. Although measurable residual disease (MRD) is increasingly used for risk stratification, optimal FLT3-ITD MRD assessment, the prognostic value of peri-transplant MRD dynamics, and their implications to transplant-related decision-making remain unclear. We conducted a multicenter retrospective study of 219 patients with FLT3-ITD-mutated AML in morphologic complete remission at transplantation, assessing peri-transplant MRD by PCR-next-generation sequencing (PCR-NGS). Pre-transplant MRD positivity (≥ 0.001% by PCR-NGS) was associated with inferior outcomes versus MRD negativity (2-year relapse-free survival [RFS], 56.8% vs. 86.5%; cumulative incidence of relapse [CIR], 30.0% vs. 6.9%; overall survival [OS], 65.9% vs. 88.4%; all p<0.001). Peri-transplant MRD dynamics outperformed single time-point assessments, identifying high-risk patients such as those with post-HCT MRD conversion. And post-HCT FLT3 inhibitor maintenance independently improved RFS (p = 0.003), with greatest benefit observed in MRD-positive patients. These findings support PCR-NGS-based molecular MRD assessment to refine risk stratification and guide individualized transplant strategies in FLT3-ITD-mutated AML.