UPDATE AML: UPdated Disease Monitoring And Treatment for Enhanced Outcomes for Pediatric AML

Inclusion Criteria: * Age Patients ≥ 1 months old to ≤ 30 years old are eligible Patients must be diagnosed with AML or myeloid sarcoma according to the 2022 WHO classification with or without extramedullary disease. Patients with AML must have 1 of the following at initial diagnosis: \- Diagnosis 1. ≥ 20% bone marrow blasts • In cases where extensive fibrosis may result in a dry tap, blast count can be obtained from touch imprints or estimated from an adequate bone marrow core biopsy. 2. \< 20% bone marrow blasts with one or more of the genetic abnormalities below: * t(8;21)(q22;q22.1) RUNX1::RUNX1T1 * inv(16)(p13.1q22) or t(16;16)(p13.1;q22) CBFB::MYH11 * Translocation involving 11q23.3 KMT2A rearrangement * t(6;9)(p23;q34.1) DEK::NUP214 * inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2) MECOM rearrangement * Megakaryoblastic with t(1;22)(p13.3;q13.3) RBM15::MRTFA * Mutated NPM1 * CEBPA bZIP mutation * t(1;22)(p13.3;q13.1) RBM15(OTT) fusion * t(7;12)(q36.3;p13.2) MNX1::ETV6 * t(8;16)(p11.2;p13.3) KAT6A::CREBBP - t(5;11)(q35.3;p15.5) NUP98::NSD1 * inv(16)(p13.3q24.3) CBFA2T3::GLIS2 * t(11;12)(p15.5;p13.5) NUP98::KDM5A * 11q23.3 partial tandem duplication (PTD) KMT2A PTD 3. A complete blood count (CBC) documenting the presence of at least 1,000/µL circulating leukemic cells (blasts) if a bone marrow aspirate or biopsy cannot be performed (i.e., a WBC count ≥ 10,000/μL with ≥ 10% blasts or a WBC count of ≥ 5,000/μL with ≥ 20% blasts). 4. Biopsy-proven myeloid sarcoma with or without bone marrow involvement. Note: patients with newly diagnosed AML, myelodysplasia-related (that are not from conditions listed in protocol section 4.2.1) ARE eligible while patients with therapy-related AML are excluded. \- Prior Therapy Patients must receive DA10+GO (Cytarabine days 1-10 + Daunorubicin days 1,3,5 \[DA10\] + Gemtuzumab ozogamcin \[GO\]) as prescribed in AAML1831 or the TXCH practice standard for Induction 1. Patients may have received any number of intrathecal treatments and have any CNS status at the time of enrollment. * Performance Status Patients must have a performance status corresponding to Karnofsky/Lansky score \>/=40. (Use Karnofsky for patients ≥16 years of age and Lanksy for patients \<16 years of age.) * Organ Function Requirements All laboratory studies to determine eligibility must be performed within seven (7) days prior to enrollment unless otherwise indicated. Laboratory values used to assess eligibility must be no older than 7 days at the start of Induction 2 therapy and need not be repeated if therapy starts within 7 days of the eligibility labs. If a post-enrollment lab value is outside the limits of eligibility, or laboratory values are \>7 days old, then the following laboratory evaluations must be re-checked within 48 hours prior to initiating therapy: bilirubin, ALT (SGPT) and serum creatinine. If the recheck is outside the limits of eligibility, the patient should be followed with periodic labs but may not receive protocol therapy until the bilirubin, ALT, and/or serum creatinine meet eligibility criteria. If \>14 days have passed from the planned start of protocol therapy and the bilirubin, ALT, and/or serum creatinine are still outside the limits of eligibility, the patient may not receive protocol therapy and rather will be considered a screen failure. Adequate renal function defined as: • An estimated creatinine clearance or GFR ≥ 60 ml/min/1.73m2. Any calculation method is acceptable, including the automatic creatinine clearance provided within the Epic EMR. Adequate liver function defined as: * A direct bilirubin \< 2 mg/dL * ALT \<5x ULN or 225 U/L, with the ULN being 45 U/L for the purpose of this study. Adequate coagulation defined as: • INR ≤ 1.5 Adequate cardiac function defined as: * Ejection fraction (EF) ≥ 50% (preferred method Biplane Simpson's EF) or if EF unavailable, shortening fraction (SF) ≥ 24%, within 14 days prior to planned start of Induction 2 therapy. * For patients with cardiac dysfunction (EF \< 50% or SF \<24% if EF is unavailable) prior to enrollment, if clinically safe and feasible, repeat echocardiogram is strongly advised in order to confirm cardiac dysfunction following clinical stabilization, particularly if occurring in the setting of sepsis or other transient physiologic stressor. If the repeat echocardiogram demonstrates an EF ≥ 50%, the patient is eligible to enroll. * Informed Consent All patients and/or their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines. Exclusion Criteria: * Patients with the following constitutional conditions are not eligible: • Fanconi anemia • Schwachman Diamond Syndrome • Telomere Disorders * Patients with constitutional trisomy 21 or with constitutional mosaicism of trisomy 21 * Germline predispositions known, or suspected by the treating physician, to increase risk of toxicity with AML therapy * Therapy-related AML * Patients with any of the following oncologic diagnoses are not eligible: • Any concurrent malignancy • Juvenile myelomonocytic leukemia • Philadelphia chromosome positive AML • Mixed phenotype acute leukemia • Acute promyelocytic leukemia • AML with FLT3 internal tandem duplication (FLT3-ITD) allelic ratio \>0.1 * Pregnancy and Breastfeeding • Female patients who are pregnant may not participate. A pregnancy test is required for female patients of childbearing potential. * Lactating females who plan to breastfeed their infants are not eligible. * Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation are not eligible.