Publication Date:
2015-10-23
Description:
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 α gene (CEBPα). 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 CEBPα among patients with NPM1 wt / FLT3 wt revealed excellent results both in patients with CEBPα 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).
Keywords:
Transplantation, Free Research Articles, Myeloid Neoplasia, Clinical Trials and Observations
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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