In Vivo Treg Expansion and Graft-Versus-Host Disease Prophylaxis

1) Determine if a GVHD prophylaxis regimen of IL-2/SIR/TAC enhances in vivo Treg
differentiation and growth; 2) Study the safety and effects of IL-2/SIR/TAC on the incidence
of acute and chronic GVHD; 3) Evaluate the influence of dual IL-2 supplementation and
mammalian target of rapamycin (mTOR) inhibition on T cell-specific signaling pathways and
the polarization of emerging T helper cells.

Inclusion Criteria:

- Patients must have an available 8/8 human leukocyte antigen (HLA)-A, -B, -C, and
-DRB1 matched-related or unrelated donor allogeneic hematopoietic peripheral blood
stem cell graft.

- Acute myeloid leukemia, myelodysplasia, acute lymphoblastic leukemia, chronic myeloid
leukemia, or myeloproliferative neoplasms requiring a matched allogeneic HSCT.

- Acute Leukemia (AML or ALL) must be in complete remission defined as: <5% marrow
blasts with no morphologic evidence of leukemia, no peripheral blasts, marrow
>20% cellular, and peripheral absolute neutrophil count >1000/µL (platelet
recovery is not required).

- Myelodysplasia (MDS) and chronic myeloid leukemia (CML): Must have <5% marrow
blasts.

- Myeloproliferative neoplasms (MPN): Must have <5% peripheral / marrow blasts.

- Adequate vital organ function:

1. Left ventricular ejection fraction (LVEF) ≥ 45% by multi gated acquisition
(MUGA) scan or ECHO

2. Forced expiratory volume at one second (FEV1), forced vital capacity (FVC), and
adjusted diffusing lung capacity oxygenation (DLCO) ≥ 50% of predicted values on
pulmonary function tests

3. Transaminases (AST, ALT) < 2 times upper limit of normal values

4. Creatinine clearance ≥ 50 cc/min.

- Performance status: Karnofsky Performance Status Score ≥ 80%

- Donor eligibility: Eligible donors will include healthy sibling, relative or
unrelated donors that are matched with the patient at HLA-A, B, C, and DRB1 by high
resolution typing.

Exclusion Criteria:

- Active infection not controlled with appropriate antimicrobial therapy

- History of HIV, hepatitis B, or hepatitis C infection

- Anti-thymocyte globulin, alemtuzumab, bortezomib, or cyclophosphamide administered
within 14 days before or planned to receive with HCT conditioning or as part of GVHD
prophylaxis in the 14 days after HCT.

- Hypersensitivity to recombinant human IL-2

- Chronic lymphocytic leukemia, Hodgkin lymphoma, and non-hodgkin lymphoma are excluded
as these malignancies may express the IL-2 receptor and pose a potential growth
signal to any present disease.

- Sorror's co-morbidity factors with total score >4