CD8+ T Cell Depletion for GVHD Prophylaxis After Peripheral Blood Stem Cell Transplantation

CD8+ T Cell Depletion as Graft Versus Host Disease Prophylaxis After HLA-Matched Unrelated Donor Non-myeloablative Peripheral Blood Stem Cell Transplantation

The purpose of this trial is to determine if selectively removing only a small subset of T cells, called CD8+ T cells, is safe and if it can reduce the risk of graft versus host disease (GVHD) without losing the anti-cancer effects.

The patient will be admitted to the hospital once a good donor is found for chemotherapy and stem cell transplant. The patient will remain in the hospital for 8 days and will receive two chemotherapy drugs (fludarabine and Busulfex) intravenously once each day for 4 days. On the third day after the patient has finished chemotherapy, the donor cells should arrive at Dana-Farber Cancer Institute and the lab will remove CD8 cells. Then the product will be given to the patient through a central line. If there are not enough stem cells in the donor product, then the CD8 cells will not be taken out, and the patient will get the whole product. Just before and after the transplant, the patient will also take tacrolimus and methotrexate to help prevent GVHD. Tacrolimus is a pill that will be taken orally two times a day. Methotrexate is a chemotherapy drug that is given intravenously on days 1, 3 and 6 after the transplant. In addition to the these drugs, participants will also take antibiotics to prevent infection and Filgrastim (G-CSF, neupogen) until their white blood cell counts are better. After the stem cell infusion, check-ups and blood tests will be performed at least once a week for 1 month. At about one month, a bone marrow biopsy to look for the donor's cells in the participants bone marrow will be performed. After the 1-month evaluation, the patient will be seen at least every 2 weeks with another bone marrow biopsy at 3-4 months after the transplant. After the patient is past 100 days since transplant, they will be followed in the clinic and have blood work done at least once a month until 6 months post transplant. The trial will end at 6 months after the transplant, but patients will be tracked for the rest of their life to look at long-term effects of this transplant.

CD8 depleted product Given through central line after treatment with fludarabine and busulfex intravenously for 4 days

To assess the initial engraftment of HLA matched unrelated donor mobilized peripheral blood stem cells depleted of CD+8 cells.

Inclusion Criteria: Hematologic malignancies that are candidates for allogeneic non-myeloablative stem cell transplantation AML or ALL in first or subsequent remission, or in resistant or untreated relapse with marrow blast < 20% of cellularity CML in first or subsequent chronic phase, or accelerated phase Myelodysplastic syndrome with < 20% marrow blasts NHL or Hodgkin's lymphoma in second or greater remission, or partial remission after salvage therapy, and in patients with marrow involvement, <20% involvement in BM CLL RAI stage 2-4, which has progressed after initial fludarabine containing therapy, and BM involvement of < 20% Multiple myeloma stage II-III, in first or subsequent plateau phase with <20% BM plasma cells Available unrelated donor who is fully HLA matched at HLA-A,B,C and DRB1 Age 18 or greater Performance status 0-2 Life expectancy of > 100 days No HLA-matched related donor available Exclusion Criteria: Myeloproliferative disorders other than CML MDS with myeloproliferative features, or CMML High grade Burkitts or Burkitts-like Non-Hodgkin's lymphoma Prior allogeneic stem cell transplant Active CNS involvement with disease Uncontrolled infection Pregnancy Evidence of HIV infection Heart failure uncontrolled my medications Total bilirubin > 2.0 mg/dl that is due to hepatocellular dysfunction AST > 2 x institutional upper limit of normal Serum creatinine > 2.0 mg/dl