Personalized r-ATG for the Improvement of Survival through Enhanced Immune Reconstitution in Patients with Acute Leukemia or Myelodysplastic Syndrome Undergoing Ex-Vivo CD34-Selected Allogeneic-HCT, (PRAISE-IR)

Inclusion Criteria

• Patients receiving first peripheral blood mobilized ex-vivo CD34-selected T cell depleted allo-HCT for the following hematologic malignant conditions: * Acute myeloid leukemia (AML) with intermediate or high-risk features in complete remission (CR)1 or relapse AML in >= CR2 ** Must have minimal residual disease (MRD) < 5% (flow cytometry, molecular and/or cytogenetics accepted) * Acute leukemias of ambiguous lineage in >= CR1 ** Must have MRD < 5% (flow cytometry, molecular and/or cytogenetics accepted) * Acute lymphoid leukemia (ALL) in CR1 with clinical, flow cytometric, or molecular features indicating a high risk for relapse, or ALL in >= CR2 ** Adult patients – recommended but not required to be MRD negative (by flow cytometry, molecular and/or cytogenetics) ** Pediatric patients – must be MRD-negative by flow cytometry, molecular and/or cytogenetics * Myelodysplastic syndromes (MDS) with least one of the following: ** Revised International Prognostic Scoring System risk score of intermediate or higher at the time of transplant evaluation ** Life-threatening cytopenia ** Karyotype or genomic changes that indicate high risk for progression to acute myelogenous leukemia, including abnormalities of chromosome 7 or 3, mutations of TP53, or complex or monosomal karyotype ** Therapy related disease or disease evolving from other malignant processes
• Able to tolerate cytoreduction (based on adequate organ function)
• Patients age: * Regimen A: 4 - 60 years * Regimen B - no age restriction
• Serum bilirubin =< 2 mg/dL, unless benign congenital hyperbilirubinemia. Patients with hyperbilirubinemia related to paroxysmal nocturnal hemoglobinuria or other hemolytic disorders are eligible with principal investigator (PI) approval
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT) < 2.5 times the upper limit of normal unless thought to be disease-related
• Alkaline phosphatase < 2.5 times the upper limit of normal unless thought to be disease-related
• Serum creatinine < 1.5 x normal for age. If serum creatinine is outside the normal range, then creatinine clearance (CrCl) > 50 mL/min/1.73 m^2 (calculated or estimated) or glomerular filtration rate (GFR) (mL/min/1.72m^2) > 30% of predicted normal for age * Age: Mean GFR +/- standard deviation (SD) (mL/min/1.73 m^2) * 1 week: 40.6 + / - 14.8 * 2 – 8 weeks: 65.8 + / - 24.8 * > 8 weeks: 95.7 +/- 21.7 * 2 – 12 years: 133 +/- 27 * 13 – 21 years (males): 140 +/- 30 * 13 – 21 years (females): 126.0 +/- 22.0
• Left ventricular ejection fraction (LVEF) >= 50% by multi-gated acquisition (MUGA) or resting echocardiogram
• Pulmonary function testing (forced expiratory volume in 1 second [FEV1] and corrected diffusion capacity of the lung for carbon monoxide [DLCO]) >= 50% predicted (pediatric patients unable to complete pulmonary function test [PFT]s will need oxygen saturation as recorded by pulse oximetry of >= 92% on room air)
• Adequate performance status: * Age >= 16 years: Eastern Cooperative Oncology Group (ECOG) =< 1 or Karnofsky 70% * Age < 16 years: Lansky 70%
• Each patient must be willing to participate as a research subject and must sign an informed consent form or legal guardian with assent as appropriate
• DONOR
• Related or Unrelated Donors: * 8/8 HLA matched at A, B, C, and DRB1 loci, as tested by deoxyribonucleic acid (DNA) analysis
• Able to provide informed consent for the donation process per institutional standards
• Meet standard criteria for donor collection (e.g. National Marrow Donor Program Guidelines or collecting center guidelines as approved by treating physician)
• Provide granulocyte colony-stimulating factor (GCSF) mobilized peripheral blood stem cells

Exclusion Criteria

• Patients with active extramedullary disease
• Patients with active central nervous system malignancy
• Uncontrolled infection at the time of allo-HCT
• Patients who have undergone previous allo-HCT
• Patient seropositivity for human immunodeficiency virus (HIV) I/II and/or human T-lymphotropic virus (HTLV) I/II
• Females who are pregnant or breastfeeding
• Patients unwilling to use contraception during the study period
• Patient or parent or guardian unable to give informed consent or unable to comply with the treatment protocol including research tests