[Prognostic significance of early assessment of minimal residual disease in acute myeloid leukemia with mutated NPM1 patients].

To explore prognostic significance of early assessment of minimal residual leukemia (MRD) in adult patients with acute myeloid leukemia (AML) with mutated NPM1. The response, NPM1 mutated transcript level after induction chemotherapy and the first 2 cycles of consolidation chemotherapy, disease-free survival (DFS) and overall survival (OS) in 137 patients with AML with NPM1 mutations of A, B and D were retrospectively analyzed. Data of 137 patients were collected, 67 were male, the median age was 49 years (16-67 years) , 107 (78.1%) had normal karyotype, 57 (41.6%) had positive FLT3-ITD mutation, the median NPM1 mutated transcript level at diagnosis was 84.1%. Among the 134 evaluable patients, 115 (85.8%) achieved a complete remission (CR) . Multivariate analyses revealed that WBC<100×10(9)/L (=0.3, 95% 0.1-0.9, =0.027) and first induction therapy with "IA10" protocol (=0.3, 95% 0.1-0.8, =0.015) were factors associated with achieving a CR. With a median follow-up period of 24 months (range, 2 to 91 months) in 77 survived CR patients, the probabilities of DFS and OS at 3 years were 48.0% and 63.9%, respectively. Multivariate analyses showed that positive FLT3-ITD (=3.2, 95% 1.6-6.7, =0.002) , high MRD level after 2 cycles of consolidation chemotherapy (NPM1 mutation transcript level <3-log reduction from the individual baseline, =23.2, 95% 7.0-76.6, <0.001) and chemotherapy or autologous hematopoietic stem cell transplantation (auto-HSCT) rather than allogeneic HSCT (allo-HSCT) (=2.6, 95% 1.0-6.6, =0.045) were the unfavorable factors affecting DFS, high MRD level at the time of achieving the first CR (NPM1 mutation transcript level <2-log reduction from the individual baseline, =2.5, 95% 1.0-6.1, =0.040) and after 2 cycles of consolidation chemotherapy (=4.5, 95% 2.0-10.3, <0.001) were the unfavorable factors affecting OS. Furthermore, DFS and OS rates at 3 years in those receiving chemotherapy or auto-HSCT were 39.7% and 59.1%, respectively; positive FLT3-ITD and high MRD level after 2 cycles of consolidation chemotherapy were independent factors associated with both shorter DFS (=3.5, 95% 1.6-7.6, =0.002 and =8.9, 95% 3.8-20.7, <0.001) and OS (=2.7, 95% 1.1-6.9, =0.036 and =3.1, 95% 1.2-8.0, =0.021) ; meanwhile, high MRD level at the time of achieving the first CR associated with shorter OS (=3.1, 95% 1.2-8.0, =0.022) . Positive FLT3-ITD mutation and high MRD level after induction or consolidation chemotherapy associated with poor outcomes in AML patients with mutated NPM1.