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Outcome of patients with distinct molecular genotypes and cytogenetically normal AML after allogeneic transplantation.

Abstract
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).
AuthorsChristoph Schmid, Myriam Labopin, Gerard Socié, Etienne Daguindau, Liisa Volin, Anne Huynh, Jean Henri Bourhis, Noel Milpied, Jan Cornelissen, Patrice Chevallier, Johan Maertens, Pavel Jindra, Didier Blaise, Stig Lenhoff, Norbert Ifrah, Frédéric Baron, Fabio Ciceri, Claude Gorin, Bipin Savani, Sebastian Giebel, Emmanuelle Polge, Jordi Esteve, Arnon Nagler, Mohamad Mohty,
JournalBlood (Blood) Vol. 126 Issue 17 Pg. 2062-9 (Oct 22 2015) ISSN: 1528-0020 [Electronic] United States
PMID26351297 (Publication Type: Journal Article)
Copyright© 2015 by The American Society of Hematology.

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