Clinical characteristics and prognosis analysis of patients with de novo ASXL1- mutated AML treated with the C- HUNAN-AML-15 protocol: A multicenter study by the South China Pediatric AML Collaborative Group

Background: ASXL1 mutation is an independent prognostic factor in adult acute myeloid leukemia (AML), but its effect on the prognosis of pediatric AML is poorly understood. Aims: This study aimed to investigate the clinical characteristics and prognostic factors of ASXL1-mutant pediatric AML from a large Chinese multicenter cohort. Methods: A total of 584 pediatric patients with newly diagnosed AML from 10 centers in South China were enrolled. The exon 13 of ASXL1 was amplified by polymerase chain reaction (PCR), and then analyzed the mutation status of the locus. (n = 59 for ASXL1-mut group, n = 487 for ASXL1-wt group). Results: ASXL1 mutations were found in 10.81% of all patients with AML. A complex karyotype was significantly less common in the ASXL1-mut AML group than in the ASXL1-wt group (1.7% vs. 11.9%, p = 0.013). Furthermore, TET2 or TP53 mutations were predominantly found in the ASXL1+ group (p = 0.003 and 0.023, respectively). The 5-year overall survival (OS) and event-free survival (EFS) of the total cohort were 76.9% and 69.9%. In ASXL1-mut AML patients, a white blood cell (WBC) count >= 50 x 10(9)/L had significantly poorer 5-year OS and EFS than a WBC count <50 x 10(9)/L (78.0% vs. 44.6%, p = 0.001; 74.8% vs. 44.6%, p = 0.003, respectively), while receiving hematopoietic stem cell transplantation (HSCT) had a higher 5-year OS and EFS (84.5% vs. 48.5%, p = 0.024; 79.5% vs. 49.3%, p = 0.047, respectively). In the multivariate Cox regression analysis, patients with high-risk AML undergoing HSCT tended to have a better 5-year OS and EFS than those receiving chemotherapy as a consolidation (HR = 0.168 and 0.260, both p < 0.001), and WBC count >= 50 x 10(9)/L or failure to achieve complete response after the first course were independent adverse predictors of OS and EFS (HR = 1.784 and 1.870, p = 0.042 and 0.018; HR = 3.242 and 3.235, both p < 0.001). Conclusion: The C-HUANA-AML-15 protocol is a well-tolerated and effective in the treatment of pediatric AML. ASXL1 mutation is not an independent adverse prognosis predictor for survival in AML, whereas ASXL1-mut patients tend to have a poor prognosis if WBC count >= 50 x 10(9)/L, but they can benefit from HSCT.

Automated summary

This study investigated the clinical characteristics and prognostic factors of ASXL1-mutant pediatric AML in a large Chinese multicenter cohort. The prevalence of ASXL1 mutations in pediatric AML patients was 10.81%. ASXL1 mutations were associated with a lower incidence of complex karyotype and a higher prevalence of TET2 or TP53 mutations. ASXL1-mutant AML patients with a high WBC count had a poorer prognosis, but could benefit from HSCT. HSCT and WBC count were independent predictors of survival in multivariate analysis.