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

This is an interventional treatment trial for Graft Versus Host Disease focused on measuring graft versus host disease, adult acute lymphoblastic leukemia in remission, adult acute myeloid leukemia in remission, secondary acute myeloid leukemia, refractory anemia with excess blasts, myelodysplastic syndromes, chronic myelogenous leukemia, refractory anemia, prolymphocytic leukemia, stage IV adult lymphoblastic lymphoma, recurrent adult Burkitt lymphoma, stage I adult Burkitt lymphoma, stage III adult Burkitt lymphoma, stage IV adult Burkitt lymphoma, follicular lymphoma, mantle cell lymphoma, chronic idiopathic myelofibrosis, secondary myelofibrosis, refractory chronic lymphocytic leukemia, recurrent small lymphocytic lymphoma, recurrent marginal zone lymphoma, marginal zone lymphoma, diffuse large cell lymphoma, anaplastic large cell lymphoma, lymphoblastic lymphoma, immunoblastic large cell lymphoma, multiple myeloma Read More

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 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.

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