Tacrolimus, Sirolimus and Methotrexate as Graft Versus Host Disease Prophylaxis After Blood Stem Cell Transplantation

Tacrolimus, Sirolimus and Methotrexate as Graft Versus Host Disease Prophylaxis After Allogeneic Non-Myeloablative Peripheral Blood Stem Cell Transplantation

The purpose of this study is to determine if the incidence of Graft vs. Host Disease (GVHD) after non-myeloablative transplantation can be reduced by using a combination of three immune suppressive medication; sirolimus, tacrolimus and methotrexate.

• Patients will be admitted to the hospital and receive chemotherapy and stem cell transplant(SCT). The total duration of hospitalization for the procedure is approximately 8 days. Once admitted the patient will receive fludarabine daily for 4 days, busulfex once daily for 4 days. Two days after chemotherapy has ended, the patient will receive the infusion of donor cells.
• Just prior to the transplant and following the transplant, patients will receive sirolimus (orally), tacrolimus (orally) and low doses of methotrexate (chemotherapy). Methotrexate will be given on days 1,3 and 6 after transplant.
• Sirolimus will be tapered beginning week 9 after transplant if there is no evidence of GVHD and will be eliminated on week 26 if clinically feasible.
• Tacrolimus will be tapered beginning week 9 after transplant if there is no evidence of GVHD and will be eliminated on week 26 if clinically feasible.
• Patients will also receive medication to help prevent possible infection.
• After stem cell infusion, patients will be examined and have blood tests weekly for 1 month. At the 1 month visit, a bone marrow biopsy will performed looking for evidence of donor cells in the bone marrow. After the one month evaluation the patient will be examined every 2 weeks and a repeat bone marrow performed 3-4 months after transplant.

Inclusion Criteria:

• Patients with hematologic malignancies who are at a high risk of complications after conventional transplantation.
• Donors (both related and unrelated) who are identical at 6 HLA loci.
• Age greater than 18
• ECOG Performance Status 0-2
• Life expectancy of greater than 100 days.

Exclusion Criteria:

• Pregnancy
• Evidence of HIV infection
• Heart failure uncontrolled by medications
• Total Bilirubin > 2.0mg/dl due to hepatocellular dysfunction
• AST > 90
• Serum creatinine > 2.0
• Cholesterol > 300 mg/dl