Clinical Study of Induction Therapy Options Based on Molecular Subtyping and MRD in Children and Adolescents With AML

Advances in risk stratification and therapy, have improved the event-free survival (EFS) and overall survival (OS) for pediatric acute myeloid leukemia (AML) with current treatment strategies. Investigators previously conducted a multicenter, randomized controlled trial (AML18) to compare the efficacy and safety of low-dose chemotherapy versus standard-dose chemotherapy. The results showed that low-dose chemotherapy was non-inferior to standard-dose chemotherapy in terms of efficacy and had fewer adverse events. However, different subtypes exhibited varying treatment responses to both chemotherapy regimens. The MRD (Measurable Residual Disease) after induction therapy in both groups had an impact on prognosis. According to the backbone of the 2018 protocol, investigators decide whether to use low-dose or standard-dose for the first induction according to the patient's fusion gene, and the second induction and subsequent treatment are adjusted according to the treatment response. Patients with the following 5 fusion genes RUNX1: RUNX1T1, CBFβ: MYH11, KMT2A: MLLT3 (AF9), KMT2A: MLLT10 (AF10), KMT2A: MLLT4 (AF6) fusion or KIT mutation will be assigned to the standard dose remission induction regimen (HHT + Ara-C + VP16), others will be assigned to the standard dose regimen (Mitoxantrone/Idarubicin + Ara-C + G-CSF). At the same time, investigators will add targeted drugs such as venetoclax, avaptitinib, and gilteritinib/sorafenib to the chemotherapy regimen and assess their safety and efficacy. Post-induction consolidation consisted of 3 to 4 cycles of standard-dose chemotherapy according to risk classification. Patients classified as high-risk are candidates for allogeneic bone marrow transplantation after 1 or 2 courses of consolidation.