MRD-guided azacitidine maintenance improves outcomes in molecularly persistent pediatric core-binding factor AML: A retrospective cohort study

Abstract Background: Relapse remains a major challenge in pediatric acute myeloid leukemia (AML), particularly in non-transplant-eligible patients. Although hypomethylating agents, such as azacitidine, are hypothesized to target residual disease, their efficacy and safety in de novo pediatric AML maintenance therapy require validation. Procedure: In this retrospective cohort study, 78 pediatric patients with de novo AML in remission after the C-HUANAN-AML 15 protocol were stratified into azacitidine maintenance (n=27; subcutaneous 75 mg/m²/day, days 1–14/cycle for 6 cycles) or observation (n=51) groups. Measurable residual disease (MRD) was longitudinally monitored using multiparameter flow cytometry (<0.1% threshold) and PCR for fusion transcripts. Outcomes included disease-free survival (DFS), overall survival (OS), and safety. Results: At a median 34.6-month follow-up, azacitidine maintenance therapy showed comparable OS (89.7% vs. 85.0%, p=0.368) and DFS (77.7% vs. 79.0%, p=0.838) to observation overall. However, intermediate-risk patients exhibited improved DFS (85.1% vs. 73.1%, p=0.305) and OS (92.9% vs. 81.6%, p=0.304). In core-binding factor-AML with baseline fusion transcripts ≥0.1%, azacitidine significantly prolonged DFS (100% vs. 62.5%, p=0.045). MRD negativity persisted in 92.6% of the azacitidine-treated patients, with one molecular relapse (0.02% blasts). Therapy was well tolerated: 40.7% had grade 2–4 myelosuppression, but all patients completed the treatment without dose reductions. Conclusions: Azacitidine maintenance is safe and is associated with sustained MRD suppression in pediatric AML, particularly in the intermediate-risk and molecularly persistent core-binding factor-AML subgroups. These findings support the use of risk-adapted MRD-guided maintenance strategies to reduce relapse and warrant validation in larger cohorts.