Abstract
ABSTRACT
This retrospective secondary analysis of the multicenter randomized CALS III‐AML18 trial evaluated the efficacy and safety of low‐dose chemotherapy (LDC) compared with standard‐dose chemotherapy (SDC) in children with M2 acute myeloid leukemia (AML‐M2). A total of 221 children were included, with 109 in the LDC arm and 112 in the SDC arm. The complete remission (CR)/CR with incomplete recovery (CRi) rates after induction I and II were 67.0% versus 70.5% (
p
= 0.568) and 84.4% versus 89.3% (
p
= 0.740), respectively. The 3 year overall survival (OS) rates were 81.2% ± 3.9% and 86.9% ± 3.3% in the LDC and SDC arms, respectively (
p
= 0.304). The corresponding 3 year relapse‐free survival (RFS) rates were 82.0% ± 3.8% and 88.1% ± 3.1% (
p
= 0.205), and the 3 year event‐free survival (EFS) rates were 62.1% ± 4.8% and 70.8% ± 4.4% (
p
= 0.218). Among patients with KIT mutations, outcomes were poorer in the LDC arm than in the SDC arm, including 3 year OS (67.1% ± 8.7% vs. 91.5% ± 4.1%,
p
= 0.011), RFS (70.6% ± 7.8% vs. 87.5% ± 4.8%,
p
= 0.038), and EFS (49.2% ± 8.7% vs. 81.0% ± 5.7%,
p
= 0.002). Among patients who developed sepsis, grade 3–5 events were less frequent in the LDC arm than in the SDC arm (33.3% vs. 78.8%,
p
< 0.001). LDC was also associated with faster neutrophil and platelet recovery, lower transfusion requirements, and reduced treatment costs during induction. No statistically significant differences in remission or survival outcomes were observed between LDC and SDC, while the LDC regimen showed a lower treatment‐related burden. These findings support further evaluation of LDC as a toxicity‐sparing induction strategy in selected pediatric patients with AML‐M2. The poorer outcomes observed among patients with KIT mutations warrant caution when considering treatment de‐intensification in this subgroup.