A Modified Dose of Rabbit Anti-thymocyte Globulin (rATG) in Children and Adults Receiving Treatment to Help Prepare Their Bodies for a Bone Marrow Transplant

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 CR1 or Relapse AML in ≥ CR2.
  * Must have 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 MRDnegative (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
* Patients age:

  * Regimen A: 4 - 60 years
  * Regimen B - no age restriction
* Adequate organ function is required, defined as follows:

  * Hepatic: Serum bilirubin ≤ 2 mg/dL, unless benign congenital hyperbilirubinemia. Patients with hyperbilirubinemia related to paroxysmal nocturnal hemoglobinuria or other hemolytic disorders are eligible with PI approval.
  * Hepatic: AST, ALT, and alkaline phosphatase \< 2.5 times the upper limit of normal unless thought to be disease-related.
  * Renal: serum creatinine \<1.5x normal for age. If serum creatinine is outside the normal range, then CrCl \> 50 mL/min/1.73m2 (calculated or estimated) or GFR (mL/min/1.72m2) \>30% of predicted normal for age.
* Normal GFR by Age

  * 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
* Cardiac: LVEF ≥ 50% by MUGA or resting echocardiogram.
* Pulmonary: Pulmonary function testing (FEV1 and corrected DLCO) ≥ 50% predicted (pediatric patients unable to complete PFTs will need oxygen saturation as recorded by pulse oximetry of ≥92% on room air).
* Adequate performance status:

  * Age ≥ 16 years: 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.

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 HIV I/II and/or 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.

Donor Inclusion Criteria:

* Related or Unrelated Donors:

  °8/8 HLA matched at A, B, C, and DRB1 loci, as tested by 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 GSCF mobilized peripheral blood stem cells