The goal of this clinical trial is to estimate the rate (probability) of complete remission or complete remission with incomplete count recovery (CR/CRi) with negative MRD after induction I and II, event-free survival (EFS), and cumulative incidence (probability) of relapse (CIR), in patients receiving molecular/precision medicine and MRD-driven remission inductions, and to assess secondarily if there is an improvement over the AML2018 protocol.

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.

Inclusion Criteria:

• 1、Newly diagnosed, untreated AML；
• 2、Under 18 years old;
• 3、Patients who have used hydroxyurea or cytarabine before diagnosis, but the dosage of cytarabine does not exceed 5 days, and the total dose does not exceed 500 mg/m2 (50 mg/m2, q12h × 5d)；
• 4、 Liver function：Tbil≤2×ULN, ALT/AST≤3×ULN, creatinine clearance ≥50ml/min；Cardiac NYHA grading<3；SaO2>92%;
• 5、No active infection (symptoms resolved for more than 3 days if infected)
• 6、ECOG<2;
• 7、Expected survival time greater than 12 weeks;
• 9、Obtain the consent of the child and/or guardian and sign the informed consent form.

Exclusion Criteria:

• 1、Acute megakaryocytic leukemia (AMKL)；
• 2、Acute promyelocytic leukemia (APL);
• 3、Treatment-related secondary AML and AML with definite MDS transformation；
• 4、Myeloproliferative neoplasm (such as Juvenile myelomonocytic leukemia, JMML);
• 5、AML secondary to congenital bone marrow failure (such as AML secondary to Fanconi anemia (FA)；
• 6、AML secondary to Down syndrome;
• 7、Only temporary chemotherapy, radiotherapy, or immunotherapy, but not systematic treatment according to the treatment plan;
• 8、 Temporary chemotherapy, radiotherapy, or immunotherapy only, not systemic therapy per protocol;
• 9、Having any significant abnormal concurrent disease or mental illness that impacts the life safety and compliance of the patient and impacts informed consent, study participation, follow-up, or interpretation of results. In this case, all the participating units are required to report directly to the responsible person for this project to jointly decide whether they meet the exclusion criteria；
• 10、Patients with very poor nutritional status, severe infection, cardiac insufficiency, and intolerance to chemotherapy;
• 11、Relapsed AML at any time；
• 12、The attending physician considers that the patient is not suitable for entering the study protocol based on the patient's physical condition, economic status, and other factors.