Clinical Significance of FLT3-ITD Variation Allele Frequency in Acute Myeloid Leukemia: A Multicenter Study

The specific prognostic impact of FLT3-ITD variant allele frequency (VAF) in acute myeloid leukemia (AML) remains unclear. In this multi-center study of 190 AML patients harboring FLT3-ITD mutations, a VAF cut-off of 40% was applied. Patients with high VAF (≥ 40%) exhibited significantly higher white blood cell counts, lactate dehydrogenase levels, and bone marrow blast percentages, alongside markedly shorter median overall survival (OS). Although high VAF was independently associated with inferior outcomes in the overall multivariate Cox regression analysis, its effect was profoundly amplified in the presence of co-mutations in NPM1 or DNMT3A. This suggests that high VAF may function not as an absolute, independent determinant, but primarily as a potent "risk amplifier." Notably, allogeneic hematopoietic stem cell transplantation (allo-HSCT) effectively mitigated this survival disadvantage. Furthermore, we characterized a non-linear relationship between VAF and mortality risk, with a sharp increase observed once the VAF burden exceeded 34%. In conclusion, a quantitative VAF ≥ 40% should be considered a context-dependent prognostic marker for risk stratification. Allo-HSCT represents a critical intervention capable of overcoming the exceedingly poor prognosis associated with high VAF.