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Updated: Jun 19, 2026
Comet Assay to Quantify DNA Damage in FLT3 Mutant-expressing 32D Cells after Exposure to Type I and Type II FLT3 Inhibitors
Published on: October 17, 2025
Outcome of patients with FLT3-mutated acute myeloid leukemia in first relapse
Farhad Ravandi1, Hagop Kantarjian, Stefan Faderl
1Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. fravandi@mdanderson.org
Abstract:
Mutations of Fms-like tyrosine kinase-3 (FLT3) have been described in about 30% of patients with acute myeloid leukemia (AML) and are associated with a shorter disease-free and overall survival after initial therapy. We sought to examine whether the presence of these mutations in relapsed disease was also associated with a poor response to salvage chemotherapy by comparing the outcome of 34 patients with diploid cytogenetics and mutated FLT3 (internal tandem duplication mutation, ITD) to 69 patients with normal karyotype and wild-type FLT3 (FLT3-WT) in first relapse. On univariate analysis, patients with mutated FLT3 were less likely to achieve a CR to first salvage compared to FLT3-WT patients (24% vs. 41%; P=0.09). Furthermore, survival was longer for the FLT3-WT patients achieving a second CR after salvage compared to FLT3-mutated patients (P=0.017). Overall, patients with mutated FLT3 had a shorter survival from the time of relapse compared to those with FLT3-WT (P<0.001). The adverse prognostic impact of FLT3 mutations appears to persist beyond the initial treatment.
Insights
Fms-like tyrosine kinase-3 (FLT3) mutations in relapsed acute myeloid leukemia (AML) patients are linked to poorer outcomes. These FLT3 mutations negatively impact response to salvage chemotherapy and overall survival.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- Fms-like tyrosine kinase-3 (FLT3) mutations occur in ~30% of acute myeloid leukemia (AML) patients.
- These mutations are associated with reduced disease-free and overall survival post-initial therapy.
Purpose of the Study:
- To investigate the prognostic significance of FLT3 mutations in patients with relapsed AML.
- To compare the efficacy of salvage chemotherapy in FLT3-mutated versus FLT3-wild-type patients.
Main Methods:
- Retrospective analysis of 34 FLT3-mutated (ITD) AML patients versus 69 FLT3-wild-type (FLT3-WT) AML patients in first relapse.
- Comparison of complete remission (CR) rates and survival outcomes between the two groups.
Main Results:
- Patients with FLT3 mutations showed a trend towards lower CR rates (24% vs. 41%, P=0.09) after first salvage chemotherapy.
- FLT3-WT patients had significantly longer survival after achieving a second CR compared to FLT3-mutated patients (P=0.017).
- Overall survival from relapse was significantly shorter for FLT3-mutated patients (P<0.001).
Conclusions:
- The adverse prognostic impact of FLT3 mutations persists in relapsed AML.
- FLT3 mutation status is a significant predictor of poor response to salvage chemotherapy and reduced survival in relapsed AML.
