Integrating FLT3-ITD molecular features with clinical risk factors improves risk stratification in acute myeloid leukemia

This study aimed to investigate the prognostic value of FLT3-ITD molecular features such as allelic ratio (AR), variant allele frequency (VAF), insertion length, insertion number and insertion site in patients with de novo acute myeloid leukemia (AML). Next-generation sequencing (NGS) was used to detect FLT3-ITD mutations in 170 patients with newly diagnosed AML (except acute promyelocytic leukemia). FLT3-ITD patients with longer insertion lengths, higher allelic ratio, and more mutations had relatively shorter overall survival(OS), though not statistically significant. Early transplantation or FLT3 inhibitor therapy led to longer OS and event-free survival(EFS). Insertion sites located in Hinge Region(HR)/β1 domain and juxtamembrane domain (JMD) derived significantly greater benefit from early FLT3 inhibitor therapy(primarily sorafenib), showing significantly prolonged overall survival. HR/β1 insertion and multiple insertions showed a trend toward being risk factors for EFS. While white blood cell count > 30 × 10⁹/L and insertion of FLT3-ITD in the HR/β1 site were independent risk factors affecting patients' overall survival. Patients with high white blood cell counts and HR/β1 insertions demonstrated shorter overall survival, while early administration of FLT3 inhibitors resulted in significantly prolonged overall survival in this population. Early transplantation and FLT3 inhibitor therapy significantly improved prognosis in AML patients. In the era of FLT3-ITD targeted drug therapy combined with transplantation, the insertion site of FLT3-ITD based on high throughput sequencing results helps predict the efficacy of FLT3 inhibitors. Integrating white blood cell count with HR/β1 insertion site can identify a high-risk patient subgroup likely to benefit from FLT3 inhibitor therapy.