Sensitive measurement of quantity dynamics of FLT3 internal tandem duplication at early time points provides

W-C Chou1, H-A Hou2, C-Y Liu3

  • 1Department of Laboratory Medicine; Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University, Taipei.

Abstract

Insights

Minimal residual disease (MRD) levels of FLT3-ITD in acute myeloid leukemia (AML) after chemotherapy are prognostic. Lower FLT3-ITD levels at early time points predict better survival, especially when combined with NPM1 mutations.

Area of Science:

  • Hematology
  • Oncology
  • Molecular Biology

Background:

  • Minimal residual disease (MRD) is a key prognostic factor in acute myeloid leukemia (AML).
  • The stability of FLT3-internal tandem duplication (FLT3-ITD) as an MRD marker has been debated due to semi-quantitative methods.
  • Early assessment of FLT3-ITD dynamics using sensitive methods may offer prognostic value.

Purpose of the Study:

  • To investigate the prognostic significance of FLT3-ITD dynamics in AML.
  • To evaluate FLT3-ITD levels at early time points after chemotherapy as predictive markers.
  • To assess the stability of FLT3-ITD in relation to NPM1 mutations.

Main Methods:

  • Quantitative real-time PCR was used to measure FLT3-ITD levels in 493 serial samples from 55 AML patients.
  • FLT3-ITD quantities were analyzed at two early time points: after induction (TP1) and after the first post-induction chemotherapy (TP2).
  • Median follow-up was 64.8 months.

Main Results:

  • Lower FLT3-ITD levels at TP2 correlated with longer overall survival (OS) and disease-free survival (DFS), irrespective of cytogenetic risk.
  • A ≥3 log reduction in FLT3-ITD at TP2 independently predicted better DFS and showed a trend toward better OS.
  • FLT3-ITD disappeared at relapse in 16.7% of patients, notably less frequent in those with mutant NPM1 (0%) compared to wild-type NPM1 (29.4%).

Conclusions:

  • Early FLT3-ITD levels post-chemotherapy provide significant prognostic information in AML.
  • FLT3-ITD is more stable in patients with concurrent NPM1 mutations.
  • Despite occasional disappearance at relapse, FLT3-ITD dynamics are valuable for predicting AML patient outcomes.