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Prognostic significance of NPM1 mutations in the absence of FLT3-internal tandem duplication in older patients with acute myeloid leukemia: A SWOG and UK National Cancer Research Institute/Medical Research Council report

Ostronoff, F., Othus, M., Lazenby, Michelle, Estey, E., Appelbaum, F. R., Evans, Anna, Godwin, J., Gilkes, Amanda F., Kopecky, K. J., Burnett, Alan, List, A. F., Fang, M., Oehler, V. G., Petersdorf, S. H., Pogosova-Agadjanyan, E. L., Radich, J. P., Willman, C. L., Meshinchi, S. and Stirewalt, D. L. 2015. Prognostic significance of NPM1 mutations in the absence of FLT3-internal tandem duplication in older patients with acute myeloid leukemia: A SWOG and UK National Cancer Research Institute/Medical Research Council report. Journal of Clinical Oncology 33 (10) , pp. 1157-1164. 10.1200/JCO.2014.58.0571

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Abstract

Purpose Younger patients with acute myeloid leukemia (AML) harboring NPM1 mutations without FLT3–internal tandem duplications (ITDs; NPM1-positive/FLT3-ITD–negative genotype) are classified as better risk; however, it remains uncertain whether this favorable classification can be applied to older patients with AML with this genotype. Therefore, we examined the impact of age on the prognostic significance of NPM1-positive/FLT3-ITD–negative status in older patients with AML. Patients and Methods Patients with AML age ≥ 55 years treated with intensive chemotherapy as part of Southwest Oncology Gorup (SWOG) and UK National Cancer Research Institute/Medical Research Council (NCRI/MRC) trials were evaluated. A comprehensive analysis first examined 156 patients treated in SWOG trials. Validation analyses then examined 1,258 patients treated in MRC/NCRI trials. Univariable and multivariable analyses were used to determine the impact of age on the prognostic significance of NPM1 mutations, FLT3-ITDs, and the NPM1-positive/FLT3-ITD–negative genotype. Results Patients with AML age 55 to 65 years with NPM1-positive/FLT3-ITD–negative genotype treated in SWOG trials had a significantly improved 2-year overall survival (OS) as compared with those without this genotype (70% v 32%; P < .001). Moreover, patients age 55 to 65 years with NPM1-positive/FLT3-ITD–negative genotype had a significantly improved 2-year OS as compared with those age > 65 years with this genotype (70% v 27%; P < .001); any potential survival benefit of this genotype in patients age > 65 years was marginal (27% v 16%; P = .33). In multivariable analysis, NPM1-positive/FLT3-ITD–negative genotype remained independently associated with an improved OS in patients age 55 to 65 years (P = .002) but not in those age > 65 years (P = .82). These results were confirmed in validation analyses examining the NCRI/MRC patients. Conclusion NPM1-positive/FLT3-ITD–negative genotype remains a relatively favorable prognostic factor for patients with AML age 55 to 65 years but not in those age > 65 years.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Publisher: American Society of Clinical Oncology
ISSN: 0732-183X
Last Modified: 25 Dec 2017 21:14
URI: http://orca.cf.ac.uk/id/eprint/84638

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