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

Authors

  • Jonathan How MD,

    1. Department of Medical Oncology and Hematology, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada
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  • Jenna Sykes MMath,

    1. Department of Biostatistics, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada
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  • Vikas Gupta MD,

    1. Department of Medical Oncology and Hematology, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada
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  • Karen W. L. Yee MD,

    1. Department of Medical Oncology and Hematology, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada
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  • Aaron D. Schimmer MD, PhD,

    1. Department of Medical Oncology and Hematology, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada
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  • Andre C. Schuh MD,

    1. Department of Medical Oncology and Hematology, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada
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  • Mark D. Minden MD, PhD,

    1. Department of Medical Oncology and Hematology, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada
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  • Suzanne Kamel-Reid PhD,

    1. Department of Pathology, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada
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  • Joseph M. Brandwein MD

    Corresponding author
    1. Department of Medical Oncology and Hematology, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada
    • Department of Medical Oncology and Hematology, Princess Margaret Hospital, 610 University Avenue, Room 5-109, Toronto, Ontario M5G 2M9, Canada

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    • Fax: (416) 946-6546


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. Cancer 2012. © 2012 American Cancer Society.

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