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

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ABSTRACT: Relapse is the predominant cause of treatment failure after allogeneic hematopoietic cell transplantation (HCT) in FLT3 gene internal tandem duplication (FLT3-ITD)-mutated acute myeloid leukemia (AML). Although measurable residual disease (MRD) is increasingly used for risk stratification, optimal FLT3-ITD MRD assessment, the prognostic value of peritransplant MRD dynamics, and their implications in 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 peritransplant MRD by polymerase chain reaction (PCR)-next-generation sequencing (NGS). Pretransplant MRD positivity (≥0.001% by PCR-NGS) was associated with inferior outcomes vs MRD negativity (2-year relapse-free survival [RFS], 56.8% vs 86.5%; cumulative incidence of relapse, 30.0% vs 6.9%; overall survival, 65.9% vs 88.4%; all P< .001). Peritransplant MRD dynamics outperformed single time point assessments, identifying patients at high risk such as those with post-HCT MRD conversion. Post-HCT FLT3 inhibitor maintenance independently improved RFS (P = .003), with greatest benefit observed in patients who were MRD-positive. These findings support PCR-NGS-based molecular MRD assessment to refine risk stratification and guide individualized transplant strategies in FLT3-ITD-mutated AML.

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