Azacitidine as maintenance therapy in pediatric de novo acute myeloid leukemia

Chunping Wu¹Chunxia Cai¹Mei Li¹Nainong Li²Yongzhi Zheng^1*Hao Zheng^1*

• ¹Department of Paeditric Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou, China
• ²Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou, China

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. 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 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. 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. Subgroup analysis suggested a trend toward improved DFS (85.1% vs. 73.1%, p=0.305) and OS (92.9% vs. 81.6%, p=0.304) in patients with intermediate risk, although the This is a provisional file, not the final typeset article difference was not significant. Among 17 patients with core-binding factor-AML with baseline fusion transcripts ≥0.1%, azacitidine maintenance therapy (n=9) significantly prolonged DFS compared to observation (n=8) (100% vs. 62.5%, p=0.045). Although 40.7% had grade 2–4 myelosuppression, all patients completed the treatment without dose reductions. In conclusion, our study suggests that azacitidine maintenance therapy may confer a benefit in sustaining molecular remission for specific subgroups of pediatric AML, particularly patients with CBF-AML and persistent measurable residual disease after induction who are ineligible for HSCT. However, the observed incidence of grade 2-4 myelosuppression underscores that the potential benefits must be weighed against the associated toxicities. The optimal dosing and scheduling of azacitidine in this setting require further investigation. Ultimately, the decision to employ maintenance therapy should be individualized, and its broader application in pediatric AML warrants validation through larger, prospective, randomized controlled trials to definitively establish its risk-benefit profile.