Journal
BLOOD
Volume 126, Issue 17, Pages 2062-2069Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2015-06-651562
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Funding
- Novartis Inc.
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To analyze the influence of distinct combinations of molecular aberrations on outcome after allogeneic hematopoietic stem cell transplantation (HSCT) for cytogenetically normal acute myeloid leukemia (CN-AML), a retrospective registry analysis was performed on 702 adults undergoing HSCT in first complete remission (CR). Patients were grouped according to presence or absence of NPM1 mutations (NPM1(mut)) and FLT3 internal tandem duplications (FLT3-ITD). Double-negative patients were evaluated for mutations of the CCAAT/enhancer binding protein a gene (CEBP alpha). The influence of genotypes on relapse, non-relapse mortality, leukemia-free survival (LFS) and overall survival (OS), and a prognostic classification combining NPM1/FLT3-ITD profile and classical risk factors were calculated. Two-year OS from HSCT was 81 +/- 5% in NPM1(mut)/FLT3(wt), 75 +/- 3% in NPM1(wt)/FLT3(wt), 66 +/- 3% in NPM1(mut)/FLT3-ITD, and 54 +/- 7% in NPM1(wt)/FLT3-ITD (P = .003). Analysis of CEBP alpha among patients with NPM1(wt)/FLT3(wt) revealed excellent results both in patients with CEBP alpha(mut) and with a triple negative genotype (2-year OS: 100%/77 +/- 3%). In a Cox-model of predefined variables, age, FLT3-ITD and >1 course of chemotherapy to reach CR were risk factors associated with inferior outcome, regardless of NPM1 mutational status, variations of transplant protocols, or development of graft-versus-host disease. In a prognostic risk classification, 2-year OS/LFS rates were 88 +/- 3%/79 +/- 4% without any, 77 +/- 2%/73 +/- 3% with one, and 53 +/- 4%/50 +/- 4 with >= 2 risk factors (P = .003/.002).
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