[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