Fabiana Ostronoff1, Megan Othus2, Michelle Lazenby2, Elihu Estey2, Frederick R Appelbaum2, Anna Evans2, John Godwin2, Amanda Gilkes2, Kenneth J Kopecky2, Alan Burnett2, Alan F List2, Min Fang2, Vivian G Oehler2, Stephen H Petersdorf2, Era L Pogosova-Agadjanyan2, Jerald P Radich2, Cheryl L Willman2, Soheil Meshinchi2, Derek L Stirewalt2. 1. Fabiana Ostronoff, Megan Othus, Elihu Estey, Frederick R. Appelbaum, Kenneth J. Kopecky, Min Fang, Vivian G. Oehler, Era L. Pogosova-Agadjanyan, Jerald P. Radich, Soheil Meshinchi, and Derek L. Stirewalt, Fred Hutchinson Cancer Research Center; Fabiana Ostronoff, Elihu Estey, Frederick R. Appelbaum, Min Fang, Vivian G. Oehler, Jerald P. Radich, and Derek L. Stirewalt, University of Washington; Stephen H. Petersdorf, Seattle Genetics, Seattle, WA; Michelle Lazenby, Anna Evans, Amanda Gilkes, and Alan Burnett, Cardiff University School of Medicine, Cardiff, United Kingdom; John Godwin, Providence Cancer Center Group and Earle A. Chiles Research Institute, Portland, OR; Alan F. List, H. Lee Moffitt Cancer Center, Tampa, FL; and Cheryl L. Willman, University of New Mexico, Albuquerque, NM. fostrono@fhcrc.org. 2. Fabiana Ostronoff, Megan Othus, Elihu Estey, Frederick R. Appelbaum, Kenneth J. Kopecky, Min Fang, Vivian G. Oehler, Era L. Pogosova-Agadjanyan, Jerald P. Radich, Soheil Meshinchi, and Derek L. Stirewalt, Fred Hutchinson Cancer Research Center; Fabiana Ostronoff, Elihu Estey, Frederick R. Appelbaum, Min Fang, Vivian G. Oehler, Jerald P. Radich, and Derek L. Stirewalt, University of Washington; Stephen H. Petersdorf, Seattle Genetics, Seattle, WA; Michelle Lazenby, Anna Evans, Amanda Gilkes, and Alan Burnett, Cardiff University School of Medicine, Cardiff, United Kingdom; John Godwin, Providence Cancer Center Group and Earle A. Chiles Research Institute, Portland, OR; Alan F. List, H. Lee Moffitt Cancer Center, Tampa, FL; and Cheryl L. Willman, University of New Mexico, Albuquerque, NM.
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 Group (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.
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 Group (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.
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