cd8+ t cell depletion for gvhd prophylaxis after peripheral blood stem cell transplantation

Conditions: Hematologic Malignancy; AML; ALL; CML; Multiple Myeloma; NHL; Hodgkin's Lymphoma

Summary: 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.

Eligibility criteria:
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

Keywords: stem cell transplant graft versus host disease gvhd cd+8 t cell depletion