• Baseline left ventricular ejection fraction (LVEF) is greater than or equal to 50% by echocardiography (echo) or multigated acquisition (MUGA) scan.

• Patients of child bearing potential should use contraception.

• Patients with a diagnosis of acute myeloid leukemia (AML), or high risk myelodysplastic syndrome (MDS) (\>= 10% blasts or International Prognostic Scoring System \[IPSS\] \>= intermediate-2) or high-risk myeloproliferative neoplasm will be eligible.

• Patients with untreated or previously untreated chronic myeloid leukemia (CML) in myeloid blast phase or (Philadelphia chromosome-positive (Ph+) AML are also eligible.

• Patients with myeloproliferative neoplasms in blast phase will be eligible.

• Patients with isolated extramedullary myeloid neoplasm will be eligible.

• Patients with active CNS (central nervous system) disease are eligible.

• Bilirubin \< 2mg/dL.

• AST (aspartate aminotransferase) and/or ALT (alanine aminotransferase) \< 3 x ULN (upper limit of normal) - or \< 5 x ULN if related to leukemic involvement.

• Creatinine \< 1.5 x ULN.

• Hyperbilirubinemia is allowed if due to Gilbert's hyperbilirubinemia.

• A negative urine pregnancy test is required within 1 week for all women of childbearing potential prior to enrolling on this trial.

• Women of childbearing potential and men must agree to use contraception prior to study entry and for the duration of study participation.

• Patient must have the ability to understand the requirements of the study and signed informed consent. A signed informed consent by the patient or his legally authorized representative is required prior to their enrollment on the protocol.

• Prior therapy for any of the cohorts may include with hydroxyurea, rescue doses of cytarabine, various combination-chemotherapy regimens, hematopoietic growth factors, azacytidine, decitabine, ATRA (all-trans retinoic acid).

• Cohort 1: Frontline cohort patients are eligible in the frontline cohort if they are untreated or previously treated already in CR if they received 3 or fewer cycles of previous chemotherapy (including either 1 induction and 2 consolidations or 2 inductions and 1 consolidation).

• Cohort 2: Salvage cohort in 1st and 2nd salvage patients are eligible in the salvage cohort 2 if they have active disease after first or second relapse or if they are in CR after previously documented first or second relapse as long as they if they have received 3 or fewer cycles of chemotherapy to achieve the most current CR.

• Cohort 3: Salvage cohort in 3rd salvage and beyond patients may be eligible in salvage cohort 3 if they have active disease after 3rd or greater relapse or if they are in CR after a previously documented relapse (3rd or greater), but may have only received 3 or fewer cycles of chemotherapy to achieve the most current CR.

• Cohort 4: Maintenance cohort: Patients in CR who are considered by treating physician to benefit from maintenance therapy are eligible for maintenance therapy with dexrazoxane combined with idarubicin plus cytarabine.