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 celldepleted allo-HCT for the following hematologic malignant conditions:

• Acute myeloid leukemia (AML) with intermediate or high-risk features in CR1 orRelapse 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, ormolecular features indicating a high risk for relapse, or ALL in ≥ CR2.

• Adult Patients - recommended but not required to be MRDnegative (by flowcytometry, molecular and/or cytogenetics).

• Pediatric Patients - Must be MRD-negative by flow cytometry, molecular and/orcytogenetics.

• Myelodysplastic syndromes (MDS) with least one of the following:

• Revised International Prognostic Scoring System risk score of intermediate orhigher at the time of transplant evaluation.

• Life-threatening cytopenia.

• Karyotype or genomic changes that indicate high risk for progression to acutemyelogenous leukemia, including abnormalities of chromosome 7 or 3, mutationsof 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 congenitalhyperbilirubinemia. Patients with hyperbilirubinemia related to paroxysmalnocturnal hemoglobinuria or other hemolytic disorders are eligible with PIapproval.

• Hepatic: AST, ALT, and alkaline phosphatase < 2.5 times the upper limit ofnormal unless thought to be disease-related.

• Renal: serum creatinine <1.5x normal for age. If serum creatinine is outsidethe 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 recordedby 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 aninformed 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 complywith 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 institutionalstandards.

• Meet standard criteria for donor collection (e.g. National Marrow Donor ProgramGuidelines or collecting center guidelines as approved by treating physician).

• Provide GSCF mobilized peripheral blood stem cells