Detectable FLT3-ITD or RAS mutation at the time of transformation from MDS to AML predicts for very poor outcomes

Talha Badar, Keyur P. Patel, Philip A. Thompson, Courtney DiNardo, Koichi Takahashi, Monica Cabrero, Gautam Borthakur, Jorge Cortes, Marina Konopleva, Tapan Kadia, Zach Bohannan, Sherry Pierce, Elias J. Jabbour, Farhad Ravandi, Naval Daver, Raja Luthra, Hagop Kantarjian, Guillermo Garcia-Manero

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Background: The molecular events that drive the transformation from myelodysplastic syndromes (MDS) to acute myeloid leukemia (AML) have yet to be fully characterized. We hypothesized that detection of these mutations at the time of transformation from MDS to AML may lead to poorer outcomes. Methods: We analyzed 102 MDS patients who were admitted to our institution between 2004 and 2013, had wild-type (wt) FLT3-ITD and RAS at diagnosis, progressed to AML, and had serial mutation testing at both the MDS and AML stages. Results: We detected FLT3-ITD and/or RAS mutations in twenty-seven (26%) patients at the time of transformation to AML. Twenty-two patients (81%) had RAS mutations and five (19%) had FLT3-ITD mutations. The median survival after leukemia transformation in patients who had detectable RAS and/or FLT3-ITD mutations was 2.4 months compared to 7.5 months in patients who retained wt RAS and FLT3-ITD (hazard ratio [HR]: 3.08, 95% confidence interval [CI]: 1.9-5.0, p < 0.0001). In multivariate analysis, FLT3-ITD and RAS mutations had independent prognostic significance for poor outcome.

Original languageEnglish (US)
Pages (from-to)1367-1374
Number of pages8
JournalLeukemia Research
Volume39
Issue number12
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

Keywords

  • AML
  • FLT3-ITD
  • Leukemic transformation
  • MDS
  • RAS

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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    Badar, T., Patel, K. P., Thompson, P. A., DiNardo, C., Takahashi, K., Cabrero, M., Borthakur, G., Cortes, J., Konopleva, M., Kadia, T., Bohannan, Z., Pierce, S., Jabbour, E. J., Ravandi, F., Daver, N., Luthra, R., Kantarjian, H., & Garcia-Manero, G. (2015). Detectable FLT3-ITD or RAS mutation at the time of transformation from MDS to AML predicts for very poor outcomes. Leukemia Research, 39(12), 1367-1374. https://doi.org/10.1016/j.leukres.2015.10.005