Details

Autor(en) / Beteiligte

• Ostronoff, Fabiana
• Othus, Megan
• Lazenby, Michelle
• Estey, Elihu
• Appelbaum, Frederick R
• Evans, Anna
• Godwin, John
• Gilkes, Amanda
• Kopecky, Kenneth J
• Burnett, Alan
• List, Alan F
• Fang, Min
• Oehler, Vivian G
• Petersdorf, Stephen H
• Pogosova-Agadjanyan, Era L
• Radich, Jerald P
• Willman, Cheryl L
• Meshinchi, Soheil
• Stirewalt, Derek L

Titel

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

Ist Teil von

• Journal of clinical oncology, 2015-04, Vol.33 (10), p.1157-1164

Ort / Verlag

United States: American Society of Clinical Oncology

Erscheinungsjahr

2015

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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 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. 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. 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.