Minhui Zeng

Background: Chronic myeloid leukemia (CML) is rare in children and often shows more aggressive features than in adults. Real‐world data on the efficacy and safety of frontline nilotinib in pediatric CML in chronic phase (CML‐CP) remain limited. Methods: This prospective multicenter real‐world study evaluated the efficacy, safety, and pharmacokinetics of frontline nilotinib in newly diagnosed pediatric CML‐CP across 26 hospitals in China between January 2023 and April 2025. Patients received nilotinib 230 mg/m ² twice daily. Primary end points were complete cytogenetic response (CCyR) at six cycles and major molecular response (MMR) at 12 cycles. Secondary end points included time to MMR, event‐free survival (EFS), and safety. Results: Among 59 enrolled patients (median age, 10.6 years), 71.8% (28/39) achieved MMR at 12 cycles and all achieved CCyR at six cycles. Median time to MMR was 6.2 (3.3, 12.2) months, and 2‐year EFS was 93.3% (84.4%–100%). Nilotinib trough concentrations (Ctrough) correlated negatively with BCR::ABL1 transcript levels at cycles 6 and 12. Patients with Ctrough >950 ng/mL were three to five times more likely to reach MMR, whereas those with Ctrough ≥1500 ng/mL had a 6.5‐fold higher risk of hyperbilirubinemia. Conclusions: Frontline nilotinib thus shows strong efficacy and manageable safety in pediatric CML‐CP. Higher drug exposure predicts deeper molecular responses but increases toxicity, supporting the potential role of therapeutic drug monitoring.

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 × 10⁹/L had significantly poorer 5‐year OS and EFS than a WBC count 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 × 10⁹/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 × 10⁹/L, but they can benefit from HSCT.