Disease free survival
The DFS was significantly higher in pediatric group than in adult group (children 74.3%±5.6% vs. adults 58.2%±5.4%, P=0.021, figure 1B1). The DFS benefit in children was also seen at 2 year interim (children 66.9%±6.1% vs. adults 55.3%±5.5%, P=0.014, supplemental figure 1B). However, when consolidation regimens were taken into consideration, the DFS was comparable between the two age groups (MDAC-based regimen: children 86.2%±5.3%, P=0.959 vs. adults 83.7%±6.7%, figure 1B2; SDAC-based regimen: children 50.3%±11.8% vs. adults 50.0%±7.7%, P=0.581, figure 1B3).
Based on multivariate analysis, both EML (with vs. without, HR 1.88, 95% CI 0.97-3.64, P=0.048) and consolidation regimens (MDAC-based vs. SDAC-based, HR 0.22,95% CI 0.12-0.42, P<0.001) were independent risk factors for DFS. Being positive in c-KIT mutations (mutant vs.WT, HR 1.80, 95% CI 0.95-3.40, P=0.095) was also associated with a trend toward lower DFS. Variables, including gender (male vs. female), age (≥14 vs. <14 years), WBC count at the time of diagnosis (≥20×109/L vs. <20×109/L), immunphenotype including CD34, CD33, CD13, CD117, HLA-DR, CD19 and CD56 (positive vs. negative), additional chromosome abnormalities (with vs. without) and FLT3-ITD status (mutant vs. WT) did not affect DFS. Detail was shown in table 3.
Multivariate analysis revealed that the adverse effects of EML and c-KIT mutations on DFS were only seen in adults (EML: with 38.7%±9.7% vs. without 66.6%±6.2%, P=0.003, figure 2B2; c-KIT mutations: mutant 44.5%±9.7% vs. WT 68.5%±7.8%, P=0.015, figure 3B2), but not in children (EML: with 61.7%±18.0% vs. without 76.2%±5.8%, P=0.205, figure B3; c-KIT mutations: mutant 68.6%±18.6% vs. WT 73.3%±6.4%, P=0.602, figure 3B3). The inferior outcome in adult cohort with EML and c-KIT mutations was not improved by consolidation treatment (supplemental figure 5 and 6).