ELN Genetic Risk Stratification Not Affect the Mid-Term Survival in Childhood AML: Report from Southern China Childhood AML Group

OBJECTIVE: To evaluate the survival of children with acute myeloid leukemia (AML) in the ELN genetic risk stratification. To explore the precise treatment and efficacy in childhood AML.

Methods: The information of genetics of 151 newly diagnosed AML children enrolled in the Southern China Childhood AML Collaboration Group from December 2014 to June 2017 were retrospectively analyzed. These patients was divided into low-risk, intermediate-risk and high-risk groups according to the ELN genetic risk stratification. All cases were treated with the Southern China Childhood AML Collaborative Group protocol. The induction of remission was not randomized using FLAG-IDA and DAE regimens for 2 courses of treatment. The consolidation therapy was performed using HAE and MidAC regimens. 20 cases underwent hematopoietic stem cell transplantation. The mediate follow-up time was 18 months. Survival analysis and Log-Rank test were investigated by Graphpad Prism software.

RESULTS: Of 151 children with AML, AML1/ETO positive in 46(30.5%) cases, CBFβ/MYH11 positive in 12(7.9%) cases, MLL gene in 18(11.9%) cases (including MLLT3-KMT2A in 7 cases). There were mutation gene FTL3/ITD in 24(15.9%) cases, ASXL1 mutation In 10(6.6%) cases, NPM1 mutation in 3(2.0%) cases and CEBPA double mutation in 4(2.6%) cases. Chromosome -7 or 7q- was found in 5(3.3%) cases. According to the ELN genetic risk stratification, 60/151(39.7%), 52/151(34.4%) and 39/151(25.8%) of patients were classified as low-risk, intermediate-risk and high-risk respectively. In the cohort of DAE induction, the CR+CRi rate was 95%, 69% and 80% in the low-risk, intermediate-risk and high-risk group. In the cohort of FLAG-IDA induction, the CR+CRi rate was 100%, 95% and 100% in the low-risk, intermediate-risk and high-risk group. The significance of CR+CRi rate only were be seen in the intermediate-risk group( P=0.02). The 2 year overall OS and DFS were 82.56% and 75.74% respectively. The 2-year DFS of the FLAG-IDA and DAE groups were 85.38% and 53.72% respectively (P=0.0004). The 2-year DFS of the LR, IR, and HR groups in the FLAG-IDA group were 89.23%, 92.29%, and 91.67% respectively, and no statistical difference was found among the groups (P=0.909). The 2-year DFS of the chemotherapy group and the hematopoietic stem cell transplantation group were 82.24% and 63.38%. There were no statistical differences between the groups.

Discussion: The FLAG-IDA induction group significantly improved DFS compared with the DAE group. Hematopoietic stem cell transplantation failed to improve the survival of children with AML in the short period in our multicentre study. Our mid-term results show that the ELN genetic risk stratification had not a significant impact on the prognosis of newly diagnosed childhood AML with high-intensity therapy.