Childhood AML Combined with AML1-ETO Fusion Gene and c-KIT or Other Mutations Had Favorable Survival Treated By the C-Huanan AML 2015 Protocol: Study in Multicenter of South of China

Abstract

Objective: To analyze the impact of AML1-ETO combined with other gene mutations on survival prognosis in children with acute myeloid leukemia (AML) who received the C-HUANAN AML 2015 protocol. Methods: Total 363 children with AML (non APL) who received chemotherapy only from 9 medical centers in South China from January 2015 to December 2020 were retrospective analyzed. The fusion genes and mutation genes spectrum in the bone marrow samples of these children were detected by the first generation and next generation gene sequencing methods. One hundred and fourteen patients had been detected the AML1-ETO fusion gene positive. All of them were treated with the C-HUANAN AML 2015 protocol including 2 groups in which each group contained 4 courses of chemotherapy(FLAG-IDA1,FLAG-IDA2,HAE MidAC versus DAE1,DAE2,HAE,MidAC). The impact of AML1-ETO fusion gene combined with other gene mutations on the prognosis and survival of children was analyzed. Result: A total of 114 AML patients with AML1-ETO fusion gene were included in this study, with a male to female ratio of 1.48:1 and a median age of 85.5 (7-169) months. Among them, there were 35 cases in the DAE group and 79 cases in the FLAG-IDA group. As of April 2021, with a median follow-up time of 21 months (1m-75ms ), 101 cases survived and 13 cases died. OS and EFS were 87.0 ± 3.4%, respectively, with EFS=85.0 ± 3.6%. There was no significant difference in overall survival (OS) and disease-free survival (EFS) between the DAE and FLAG-IDA group of (OS: 86.0 ± 6.5% vs 87.4 ± 4.0%)（ χ 2=0.000, P=0.995), EFS: 79.0 ± 7.6% vs 87.6 ± 3.9%（ χ 2=0.636, P=0.425). Survival analysis of AML1-ETO combined with c-KIT mutation negative or positive(n=33) showed no difference in prognosis (OS: 85.0 ± 4.2% vs 92.4 ± 5.3%)（ χ 2=0.967, P=0.325), EFS: 82.2 ± 4.5% vs 92.4 ± 5.3%（ χ 2=1.602, P=0.206); There was no difference in the prognosis between FLT3-ITD mutation negative and FLT3-ITD gene positive patients(n=8) (OS: 88.0 ± 3.4% vs 75.0 ± 15.3%)（ χ 2=1.516, P=0.218), EFS: 85.5 ± 3.7% vs 75.0 ± 15.3%（ χ 2=1.128, P=0.288); There was no difference in the prognosis between ASXL1 mutation negative and ASXL1 gene positive patients(n=14) (OS: 85.3 ± 3.8% vs 100.0%)（ χ 2=1.872, P=0.171), EFS: 83.0 ± 4.0% vs 100.0%（ χ 2=2.169, P=0.141); There was no difference in the prognosis between WT1 mutation negative and positive patients (n=34) (OS: 86.9 ± 3.9% vs 87.1 ± 7.0%)（ χ 2=0.156, P=0.693), EFS: 85.6 ± 4.0% vs 84.1 ± 7.3%（ χ 2=0.021, P=0.885); There was no difference in the prognosis between negative and positive NRAS mutations (n=13)(OS: 86.6 ± 3.6% vs 92.3 ± 7.4%)（ χ 2=0.033, P=0.856), EFS: 84.4 ± 3.9% vs 92.3 ± 7.4%（ χ 2=0.118，P=0.731). Conclusion: Combination of c-KIT or FLT3-ITD or ASXL1 or WT1 or NRAS gene mutations with AML1-ETO fusion gene in Childhood AML treated by the C-HUANAN AML protocol did not affected patients'survival.