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  • Title: Influence of FLT3-internal tandem duplication allele burden and white blood cell count on the outcome in patients with intermediate-risk karyotype acute myeloid leukemia.
    Author: How J, Sykes J, Gupta V, Yee KW, Schimmer AD, Schuh AC, Minden MD, Kamel-Reid S, Brandwein JM.
    Journal: Cancer; 2012 Dec 15; 118(24):6110-7. PubMed ID: 22736495.
    Abstract:
    BACKGROUND: In patients with acute myeloid leukemia (AML), testing for fms-like tyrosine kinase-3 (FLT3)-internal tandem duplication (FLT3-ITD) and nucleophosmin-1 (NPM1) mutations can allow for further prognostic subclassification, but less is known about the effects of FLT3-ITD allele burden and presenting white blood cell count (WBC) within molecular subgroups. METHODS: The authors retrospectively assessed 206 adult patients who had AML with an intermediate-risk karyotype and who received treatment on a uniform induction and consolidation chemotherapy regimen. RESULTS: The presenting WBC was a prognostic factor for survival only in patients who had an FLT3-ITD mutation. On multivariate analysis, after correcting for age, WBC, secondary AML, and blast percentage, nucleophosmin-1 (NPM1)-mutated/FLT3-ITD-negative patients had superior overall survival compared with patients in the other molecular subgroups. Patients who had FLT3-ITD mutations had an inferior overall survival compared with patients who had NPM1 wild-type/FLT3-negative disease, and patients who had low or intermediate levels of the FLT-ITD of mutant allele had overall and disease-free survival similar to those in patients who had high-level mutations. CONCLUSIONS: NPM1 and FLT3-ITD status, age, WBC, and secondary AML were identified as important prognostic variables that can help to risk stratify patients with AML who have intermediate-risk cytogenetics. FLT3 allele burden had no significant influence on outcomes after correcting for other variables.
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