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Impact of FLT3(ITD) mutant allele level on relapse risk in intermediate-risk acute myeloid leukemia

David C Linch1, Robert K Hills2, Alan K Burnett2

  • 1Department of Haematology, University College London Cancer Institute, London, United Kingdom; and.

Blood
|May 24, 2014
PubMed

Insights

Patients with acute myeloid leukemia (AML) and NPM1 mutations may face increased relapse risk if FLT3 internal tandem duplications (FLT3(ITD)) are present, regardless of FLT3(ITD) levels. Further research is needed before classifying these cases as low-risk.

Area of Science:

  • Hematology
  • Oncology
  • Molecular Biology

Background:

  • The prognostic significance of FLT3 internal tandem duplications (FLT3(ITD)) in acute myeloid leukemia (AML) with concomitant NPM1 mutations is debated.
  • Previous studies suggest that low FLT3(ITD) levels might not worsen prognosis in NPM1-mutated AML, but this remains controversial.

Purpose of the Study:

  • To investigate the impact of FLT3(ITD) levels on relapse risk in younger adult patients with intermediate-risk AML and NPM1 mutations.
  • To clarify the therapeutic implications of FLT3(ITD) and NPM1 mutation status in AML prognosis.

Main Methods:

  • Analysis of FLT3(ITD) and NPM1(MUT) levels in 1609 younger adult cases of cytogenetically intermediate-risk AML.
  • Assessment of cumulative incidence of relapse based on FLT3(ITD) and NPM1(MUT) status.
  • Adjustment of FLT3(ITD) levels for leukemic cell purity using NPM1(MUT) levels.

Main Results:

  • The presence of FLT3(ITD) increased the cumulative incidence of relapse in NPM1(MUT) cases.
  • Relapse risk did not significantly differ based on FLT3(ITD) levels, even after adjusting for NPM1(MUT) levels.
  • Low-level FLT3(ITD) in NPM1(MUT) AML did not appear to confer a good prognosis.

Conclusions:

  • NPM1-mutated AML cases with low-level FLT3(ITD) should not be automatically classified as low-risk for consolidation therapy decisions.
  • Further studies are required to accurately stratify relapse risk in this AML subgroup.
  • The findings highlight the complex interplay between FLT3(ITD) and NPM1 mutations in AML prognosis.

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