Outcome and risk factor analysis of molecular subgroups in cytogenetically normal AML treated by allogeneic transplantation
Menée sur 702 patients atteints d'une leucémie myéloïde chronique sans anomalie cytogénétique ayant reçu une greffe allogénique de cellules souches hématopoïétiques, cette étude rétrospective met notamment en évidence une association entre la présence de duplications internes en tandem de FLT3 et la survie des patients
In AML with normal cytogenetics, age, response to induction, and FLT3-ITD allow for an estimate of outcome after allogeneic HSCT in CR1.Neither variation of classical transplant techniques, nor development of cGvHD outweighs the negative impact of FLT3-ITD. 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 CN-AML 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 CEBPαmut (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.
Blood , résumé, 2014