TY - JOUR
T1 - Prognostic significance of NPM1 mutations in the absence of FLT3-internal tandem duplication in older patients with acute myeloid leukemia
T2 - A SWOG and UK national cancer research institute/medical research council report
AU - Ostronoff, Fabiana
AU - Othus, Megan
AU - Lazenby, Michelle
AU - Estey, Elihu
AU - Appelbaum, Frederick R.
AU - Evans, Anna
AU - Godwin, John
AU - Gilkes, Amanda
AU - Kopecky, Kenneth J.
AU - Burnett, Alan
AU - List, Alan F.
AU - Fang, Min
AU - Oehler, Vivian G.
AU - Petersdorf, Stephen H.
AU - Pogosova-Agadjanyan, Era L.
AU - Radich, Jerald P.
AU - Willman, Cheryl L.
AU - Meshinchi, Soheil
AU - Stirewalt, Derek L.
N1 - Publisher Copyright:
© 2015 by American Society of Clinical Oncology.
PY - 2015/4/1
Y1 - 2015/4/1
N2 - 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.
AB - 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.
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U2 - 10.1200/JCO.2014.58.0571
DO - 10.1200/JCO.2014.58.0571
M3 - Article
C2 - 25713434
AN - SCOPUS:84927647785
SN - 0732-183X
VL - 33
SP - 1157
EP - 1164
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 10
ER -