• Eligible patients with a histopathological confirmed diagnosis of hematologic malignancy in one of the following categories:

‣ Acute myelogenous leukemia:

• Patients with de novo or secondary disease in unfavorable risk group including poor risk cytogenetics according to National Comprehensive Cancer Network (NCCN) guidelines for AML i.e., monosomal karyotype, -5, 5q-, -7, 7q-, 11q23-non t (9;11), inv (3), t (3;3),t (6;9), t (9;22) and complex karyotypes (≥ 3 unrelated abnormalities), or all patient in intermediate risk groups accept patients with FLT3-NPM1+ disease

∙ Patients with active disease

∙ Patients with chemosensitive active disease

⁃ Acute lymphocytic leukemia:

• Patients with de novo or secondary disease according to NCCN guidelines for ALL hypoploidy (\< 44 chromosomes); t (v;11q23): MLL rearranged; t (9;22) (q34;q11.2); complex cytogenetics (5 or more chromosomal abnormalities); high white blood cell (WBC) at diagnosis (≥ 30,000 for B lineage or ≥ 50,000 for T lineage); iAMP21loss of 13q, and abnormal 17p

∙ Patients with active disease

∙ Patients with chemosensitive active disease

⁃ Myelodysplastic syndrome in high-intermediate (int-2) and high risk categories

• Patients ≥ 12 years and \< 55 years are also included if they are not candidates for myeloablative conditioning regimens due to comorbidities

• Karnofsky or Lansky performance status of ≥ 70

• A pretreatment measured creatinine clearance (absolute value) of ≥ 60 ml/minute

• Patients must have a serum bilirubin ≤ 2.0 mg/dl

• Serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamic-pyruvic transaminase (SGPT) ≤ 2.5 times the institutional upper limits of normal

• Ejection fraction measured by echocardiogram or multigated acquisition (MUGA) ≥ 50%

• Carbon monoxide diffusing capacity (DLCO) and forced expiratory volume FEV1 \> 50% predicted

• PATIENT-SPECIFIC INCLUSION CRITERIA

• Patients should have discontinued all previous intensive therapy, chemotherapy or radiotherapy for 2 weeks prior to commencing therapy on this study

‣ NOTE: low dose chemotherapy or maintenance chemotherapy given within 7 days of planned study enrollment is permitted; these include hydroxyurea, 6-meraptopurine, oral methotrexate, vincristine, oral etoposide, and tyrosine kinase inhibitors (TKIs); FLT-3 inhibitors can also be given up to 3 days before conditioning regimen

⁃ All patients with prior radiation treatment to the lung, liver, and kidney will be excluded; for other scenarios of prior radiation treatment, up to 2000 cGY at 2 gray Gy per day will be allowed; inclusion of patients with previous radiation exposure will be determined based on the radiation oncologist MD evaluation and judgment

• DONOR: Arm A: All candidates for this study must have an human leukocyte antigen (HLA) (A, B, C, and DR) identical sibling who is willing to donate primed blood stem cells (preferred) or bone marrow, or have a 10/10 (A, B, C, DR and DQ) allele matched unrelated donor; DQ or DP mismatch is allowed per discretion of the principal investigator

• DONOR: Arm B: The recipient must have a related donor genotypically HLA-A, B, C and DRB1 loci haploidentical to the recipient; no HLA matched sibling or matched unrelated donor is available; DSA is allowed with desensitization done if recommended by donor selection committee (DSC) per City of Hope (COH) standard operating procedures (SOP)

• DONOR: Both arms: All donors in both arms should be evaluated and approved by DSC