Article (Scientific journals)
Outcome and risk factor analysis of molecular subgroups in cytogenetically normal AML treated by allogeneic transplantation
SCHMID, Christoph; LABOPIN, Myriam; SOCIE, Gerard et al.
2015In Blood, 126, p. 2062-2069
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Abstract :
[en] Patients with cytogenetically normal acute myeloid leukemia (CN-AML) can be subdivided by molecular mutations. However, data on the influence of combinations of different aberrations on outcome after allogeneic hematopoietic stem cell transplantation (HSCT) is limited. Therefore, we performed a retrospective registry analysis on 702 adults with CNAML undergoing HSCT in first complete remission (CR). Patients were grouped according to presence or absence of NPM1 mutations (NPM1mut) 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. 2y-OS from HSCT was 81±5% in NPM1mut/FLT3wt (n=68), 75±3% in NPM1wt/FLT3wt (n=290), 66±3% in NPM1mut/FLT3-ITD (n=269) and 54±7% in NPM1wt/FLT3-ITD (n=75; p=0.003). Analysis of CEBPα among patients with NPM1wt/FLT3wt revealed excellent results both in patients with CEBPα mut (n=13, 2y-OS:100%), and with a triple negative genotype (n=138, 2y-OS:77±3%). In a Cox-model of predefined factors, older age, presence of FLT3-ITD and >1 course of chemotherapy to reach CR were associated with inferior outcome. 2y-OS/LFS were 88±3%/79±4% in patients without any, 77±2%/73±3% with one, and 53±4%/50±4 with>=2 risk factors (p=0.002 for LFS, p=0.003 for OS). Hence, FLT3-ITD proofed to be the decisive molecular marker for outcome after HSCT for CN-AML in CR1, regardless of NPM1 mutational status, variations of transplant protocols, or development of GvHD. Age, FLT3-ITD and response to induction chemotherapy allow for a prognostic risk classification.
Disciplines :
Hematology
Author, co-author :
SCHMID, Christoph
LABOPIN, Myriam
SOCIE, Gerard
DAGUINDAU, Etienne
VOLIN, Liisa
HUYNH, Anne
BOURHIS, Jean Henri
MILPIED, Noel
CORNELISSEN, Jan
CHEVALLIER, Patrice
MAERTENS, Johan
JINDRA, Pavel
BLAISE, Didier
LENHOFF, Stig
IFRAH, Norbert
BARON, Frédéric  ;  Centre Hospitalier Universitaire de Liège - CHU > Hématologie clinique
CICERI, Fabio
GORIN, Claude
SAVANI, Bipin
GIEBEL, Sebastian
POLGE, Emmanuelle
ESTEVE, Jordi
NAGLER, Arnon
MOHTY, Mohamad
More authors (14 more) Less
Language :
English
Title :
Outcome and risk factor analysis of molecular subgroups in cytogenetically normal AML treated by allogeneic transplantation
Publication date :
September 2015
Journal title :
Blood
ISSN :
0006-4971
eISSN :
1528-0020
Publisher :
American Society of Hematology, Washington, United States - District of Columbia
Volume :
126
Pages :
2062-2069
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 12 November 2015

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