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

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 HSC source must be HLA matched at 4-6 HLA- A and B (at low to intermediate resolution) and DRB1 (at high resolution), and the units must be HLA matched at 4-6 HLA- A, B, DRB1 antigens with each other. Total cryopreserved HSC graft cell dose must be \>2.5 x 107 nucleated 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 antigens with 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 preceding myelodysplastic syndrome (MDS), high risk cytogenetics such as those associated with MDS or complex karyotype, or \>2 cycles to obtain complete remission (CR); second or greater CR. Must be in remission by morphology (\<5% blasts within normocellular 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 anemia with severe pancytopenia or high risk cytogenetics. Blasts must be \< 10% by a representative bone marrow aspirate morphology (otherwise induction chemotherapy to achieve \< 10% blasts is required pre-transplant).

Advanced myelofibrosis

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

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

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

Lymphoblastic lymphoma, Burkitt's lymphoma, and other high-grade NHL after initial therapy 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 response lasting less than 6 months, or β-2 microglobulin \> 3 mg/L, may be considered for this protocol after initial therapy.

Recipients will have a Karnofsky score \> 80% and have acceptable organ function ie creatinine \< 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 \> 40 ml/min to be eligible).

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

What this study is about