Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has improved the prognosis of patients with acute myeloid leukemia (AML) harboring FLT3-internal tandem duplication (FLT3-ITD) mutations. However, relapse still occurs in 15–35% of these patients post-transplant. Currently, capillary electrophoresis (CE)-based fragment analysis is widely used to detect FLT3-ITD post-transplant, but it lacks sufficient sensitivity, often detecting FLT3-ITD only after relapse. This limitation underscores the need for more sensitive detection techniques to identify minimal residual disease earlier, allowing for timely intervention and potentially improving patient outcomes. We enrolled 2,711 patients with malignant hematologic diseases who underwent HSCT between September 2017 and September 2024 in the NICHE-BMT cohort. We then evaluated whether ultra-sensitive next-generation sequencing (NGS) for FLT3-ITD (limit of detection: 10⁻⁶) on day +30 post-HSCT could identify patients at a high risk of relapse and inform decisions regarding maintenance therapy. Among the 136 patients, all of whom were CE-negative for FLT3-ITD, thirty-seven patients (27.2%) were found to have detectable FLT3-ITD clones on day +30 using high-sensitivity NGS. These patients exhibited a significantly higher cumulative incidence of post-HSCT measurable residual disease (MRD) positivity by multiparameter flow cytometry (40.3% vs. 18.8%, p = 0.001). Notably, FLT3-ITD–positive patients who received maintenance therapy had a significantly lower 2-year cumulative incidence of relapse (CIR) compared to those who did not (8.3% vs. 54.3%, p = 0.006). Conversely, FLT3-ITD–negative patients without pre-transplant high-risk features (2022 European LeukemiaNet adverse-risk group, relapsed/refractory AML, MRD or molecular positivity pre-HSCT) had comparable 2-year CIR regardless of maintenance therapy (6.3% vs. 4.8%, p = 0.784). This is the first study to demonstrate that the detection of minimal FLT3-ITD clones at day +30 post-HSCT can reliably stratify relapse risk in AML patients and provide a strong rationale for personalized post-transplant maintenance therapy.

This content is only available as a PDF.
2025
Sign in via your Institution