Umbilical Cord Blood T-Regulatory Cell Infusion Followed by Donor Umbilical Cord Blood Transplant in Treating Patients With High-Risk Leukemia or Other Hematologic Diseases

Inclusion Criteria: Patient and Donor Demographic Criteria

• Patient must be 18-45 years of age.

• Patients must have three partially HLA matched UCB units. Units identified as the HSCsource must be HLA matched at 4-6 HLA- A and B (at low to intermediate resolution) andDRB1 (at high resolution), and the units must be HLA matched at 4-6 HLA- A, B, DRB1antigens with each other. Total cryopreserved HSC graft cell dose must be >2.5 x 107nucleated cells per kilogram recipient body weight. Also, the two umbilical cord blood (UCB) units must be ABO-matched.

• The UCB unit identified as the Treg source must be HLA matched at 4-6 HLA antigenswith the patient (without an HLA or ABO matching criterion with the UCB HSC source). Disease Criteria

• Patients must have a hematological malignancy as listed below:

• Acute myelogenous leukemia: high risk CR1 (as evidenced by precedingmyelodysplastic syndrome (MDS), high risk cytogenetics such as those associatedwith MDS or complex karyotype, or >2 cycles to obtain complete remission (CR);second or greater CR. Must be in remission by morphology (<5% blasts withinnormocellular marrow).

• Acute lymphocytic leukemia: high risk CR1 as evidenced by high risk cytogenetics [t(9;22), t (1:19), t(4;11) or other MLL rearrangements] or > 1 cycle to obtain CR;second or greater CR.

• Chronic myelogenous leukemia resistant to imatinib therapy

• Myelodysplasia (MDS) IPSS Int-2 or High risk (i.e. RAEB, RAEBt) or refractory anemiawith severe pancytopenia or high risk cytogenetics. Blasts must be < 10% by arepresentative bone marrow aspirate morphology (otherwise induction chemotherapy toachieve < 10% blasts is required pre-transplant).

• Advanced myelofibrosis

• Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), marginal zoneB-cell lymphoma or follicular lymphoma that have progressed after at least two priortherapies. Patients with bulky disease (nodal mass greater than 5 cm) should beconsidered for debulking chemotherapy before transplant.

• Lymphoplasmacytic lymphoma, mantle-cell lymphoma, prolymphocytic leukemia are eligibleafter initial therapy in CR1+ or PR1+.

• Large cell non-Hodgkins lymphoma (NHL) > CR2/> PR2. Patients in CR2/PR2 with initialshort remission(<6 months) are eligible.

• Lymphoblastic lymphoma, Burkitt's lymphoma, and other high-grade NHL after initialtherapy if stage III/IV in CR1/PR1 or after progression if stage I/II <1 year.

• Multiple myeloma beyond PR2. Patients with chromosome 13 abnormalities, first responselasting less than 6 months, or β-2 microglobulin > 3 mg/L, may be considered for thisprotocol after initial therapy.

• Recipients will have a Karnofsky score > 80% and have acceptable organ function iecreatinine < 2.0, bilirubin, AST/ALT, ALP < 2 x normal, pulmonary function > 50%normal, left ventricular ejection fraction > 45%. Note: All patients with a creatinine > 1.2 or a history of renal dysfunction must have creatinine clearance (must be > 40ml/min to be eligible).

• Recipients will sign informed consent approved by the Committee on the Use of HumanSubjects at the University of Minnesota.

Exclusion Criteria:

• Pregnant or breastfeeding

• Evidence of HIV infection or known HIV positive serology

• Current active infection

• Available HLA matched sibling donor.

• CML in active blast crisis