Combination Chemotherapy, Tacrolimus, and Mycophenolate Mofetil in Treating Patients Who Are Undergoing a Donor Bone Marrow Transplant For Hematologic Cancer

• Dose Finding [ Time Frame: Day 100 ] [ Designated as safety issue: Yes ]

  To find the optimal dose of post-grafting immunosuppression with high-dose cyclophosphamide (Cy), FK-506 and MMF following myeloablative fully HLA-matched related or unrelated BMT for the patients with hematological malignancies who are at high risk of relapse.

  To estimate the incidence and severity of acute GVHD and other toxicities following myeloablative fully HLA-matched related or unrelated BMT using this approach for the patients with hematological malignancies

  
  

• Immune reconstitution and disease control [ Time Frame: Survival ] [ Designated as safety issue: No ]

  To evaluate immune reconstitution following HLA-matched related or unrelated myeloablative BMT and post-grafting immunossuppression with high dose Cy, FK-506 and MMF.

  To evaluate disease control after myeloablative fully HLA-matched related or unrelated BMT for the patients with hematological malignancies who are at high risk of relapse when Cy is included in the post-grafting immune suppression

  
  

OBJECTIVES:

Primary

• Determine the optimal dose of post-transplant immunosuppression comprising high-dose cyclophosphamide, tacrolimus, and mycophenolate mofetil administered after myeloablative conditioning chemotherapy comprising busulfan and cyclophosphamide followed by allogeneic bone marrow transplantation in patients with high-risk hematologic malignancies.
• Determine the incidence and severity of acute graft-versus-host disease in patients treated with this regimen.
• Determine other toxic effects of this regimen in these patients.

Secondary

• Determine immune reconstitution in patients treated with this regimen.
• Determine disease control in patients treated with this regimen.

OUTLINE: This is a pilot study. Patients are stratified according to age (≤ 19 years old vs > 19 years old).

• Myeloablative conditioning chemotherapy: Patients receive busulfan IV or orally 4 times daily on days -7 to -4 OR days -6 to -3 and cyclophosphamide IV over 1 hour once daily on days -3 to -1 OR days -2 and -1.
• Allogeneic bone marrow transplantation: Patients undergo allogeneic bone marrow transplantation on day 0.

• Immunosuppression therapy: Patients receive 1 of the following immunosuppressive treatment regimens:

  • Regimen 1: Patients receive high-dose cyclophosphamide IV over 1 hour on day 3.
  • Regimen 2: Patients receive high-dose cyclophosphamide IV over 1 hour on days 3 and 4.
  • Regimen 3: Patients receive high-dose cyclophosphamide as in regimen 2 and oral mycophenolate mofetil three times daily on days 5-35.
  • Regimen 4: Patients receive high-dose cyclophosphamide as in regimen 2 and mycophenolate mofetil as in regimen 3. Patients also receive tacrolimus IV or orally twice daily on days 5-50.

After completion of study transplantation, patients are followed at 30 and 60 days, 6 months, 1 year, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 30-60 patients (approximately 5 per immunosuppressive treatment regimen) will be accrued for this study.