Literature DB >> 21523727

Prognostic value of FLT3 mutations among different cytogenetic subgroups in acute myeloid leukemia.

Fabio P S Santos1, Dan Jones, Wei Qiao, Jorge E Cortes, Farhad Ravandi, Elihu E Estey, Dushyant Verma, Hagop Kantarjian, Gautam Borthakur.   

Abstract

BACKGROUND: The impact of FMS-like tyrosine kinase 3 (FLT3) mutations and mutation burden among cytogenetic subgroups of patients with acute myeloid leukemia (AML) other than normal karyotype (NK) AML is unclear.
METHODS: Patients with newly diagnosed AML were divided among 3 cytogenetic subgroups: core binding factor (CBF) AML, NK-AML, and poor-risk AML.
RESULTS: In total, 481 patients were included: 13% had, CBF-AML, 57% had NK-AML, and 30% had poor risk AML, and the frequency of any FLT3 mutations was 20%, 32%, and 7.6% in the respective cytogenetic subgroups. FLT3 mutation did not have an impact on event-free survival (EFS) in patients with CBF-AML (P = .84) and poor-risk AML (P = .37). In patients with NK-AML, EFS was worse in the FLT3-internal tandem duplication (ITD) group (20 weeks vs 41 weeks; P < .00,001) but not in the FLT3-tyrosine kinase domain (TKD) point mutation group (61 weeks vs 41 weeks; P = .15). Worse EFS and overall survival (OS) were observed among patients with NK-AML and higher FLT3-ITD burden but not among patients with FLT3-TKD mutation. In multivariate analysis, FLT3-ITD mutation was prognostic of EFS in patients with NK-AML (hazard ratio, 3.1; P = .03).
CONCLUSIONS: FLT3 mutations did not have a prognostic impact in patients with AML who had good-risk and poor-risk karyotypes. In patients with NK-AML, FLT3-ITD mutations led to worse survival, which was even worse among patients who had high mutation burden. 2010 American Cancer Society.

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Year:  2010        PMID: 21523727      PMCID: PMC4184429          DOI: 10.1002/cncr.25670

Source DB:  PubMed          Journal:  Cancer        ISSN: 0008-543X            Impact factor:   6.860


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