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. 2011 May 15;117(10):2145-55.
doi: 10.1002/cncr.25670. Epub 2010 Nov 29.

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

Fabio P S Santos  1 , Dan Jones, Wei Qiao, Jorge E Cortes, Farhad Ravandi, Elihu E Estey, Dushyant Verma, Hagop Kantarjian, Gautam Borthakur
Affiliations

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

Fabio P S Santos et al. Cancer. .

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.

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Figures

Figure 1
Figure 1
Event Free Survival (EFS) curves. (a). Core Binding Factor associated acute myeloid leukemia (AML). (b). Normal Karyotype-AML (wt-FLT3, FLT3-ITD and FLT3-TKD). (c). Poor Risk AML.
Figure 1
Figure 1
Event Free Survival (EFS) curves. (a). Core Binding Factor associated acute myeloid leukemia (AML). (b). Normal Karyotype-AML (wt-FLT3, FLT3-ITD and FLT3-TKD). (c). Poor Risk AML.
Figure 1
Figure 1
Event Free Survival (EFS) curves. (a). Core Binding Factor associated acute myeloid leukemia (AML). (b). Normal Karyotype-AML (wt-FLT3, FLT3-ITD and FLT3-TKD). (c). Poor Risk AML.
Figure 2
Figure 2
Overall Survival (OS) curves. (a). CBF-AML (b). NK-AML (wt-FLT3, FLT3-ITD and FLT3-TKD). (c). Poor Risk AML.
Figure 2
Figure 2
Overall Survival (OS) curves. (a). CBF-AML (b). NK-AML (wt-FLT3, FLT3-ITD and FLT3-TKD). (c). Poor Risk AML.
Figure 2
Figure 2
Overall Survival (OS) curves. (a). CBF-AML (b). NK-AML (wt-FLT3, FLT3-ITD and FLT3-TKD). (c). Poor Risk AML.
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