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Updated: Jun 10, 2026

Detection and Monitoring of Tumor Associated Circulating DNA in Patient Biofluids
Published on: June 8, 2019
Sensitive measurement of quantity dynamics of FLT3 internal tandem duplication at early time points provides
1Department of Laboratory Medicine; Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University, Taipei.
Background:
The level of minimal residual disease (MRD) in acute myeloid leukemia (AML) at early time points (TPs) may be an important prognostic factor. Although internal tandem duplication of FLT3 (FLT3-ITD) as an MRD marker has been questioned for its instability based on semi-quantitative methods, we hypothesized that FLT3-ITD dynamics measured by sensitive quantitative real-time PCR at early TPs before appearance of instability may provide prognostic information.
Patients And Methods:
We measured mutant quantity in 493 serial samples from 55 patients with a median follow-up time of 64.8 months. The FLT3-ITD quantities after induction (TP1) and after the first post-induction chemotherapy (TP2) were analyzed.
Results:
We found that lower FLT3-ITD levels at TP2 predicted longer overall survival (OS) and disease-free survival (DFS) regardless of cytogenetic risk. Multivariate analysis showed that ≥3 log reduction of FLT3-ITD at TP2 independently predicted better DFS and a trend toward better OS. FLT3-ITD disappeared at relapse in 16.7% of patients and none in those harboring mutant NPM1 compared with 29.4% in those with wild-type NPM1 (P = 0.032).
Conclusions:
Though the mutation may disappear at relapse in a few patients, FLT3-ITD levels at early TPs after chemotherapy provide prognostic information. FLT3-ITD is significantly more stable in those with mutant NPM1.
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.

