Busulfan, Fludarabine, and Total-Body Irradiation in Treating Patients Who Are Undergoing a Donor Stem Cell Transplant for Hematologic Cancer

OBJECTIVES:

Primary

To assess safety and toxicity of the addition of busulfan added to an established fludarabine and low-dose total-body irradiation (TBI) conditioning regimen for non-myeloablative allogeneic transplantation in patients with hematologic malignancies. (Phase I)
To assess the non-relapse mortality 1-year after conditioning with busulfan and fludarabine/TBI in patients with hematologic malignancies at moderate to high risk for graft rejection and/or relapse of underlying disease. (Phase II)

Secondary

To assess overall survival 1-year survival. (Phase II)
To assess the incidence of graft rejection. (Phase II)
To assess the incidence of grade II-IV acute graft-vs-host disease (GVHD) and chronic extensive GVHD. (Phase II)
To assess rates of disease progression and/or relapse-related mortality. (Phase II)
To determine non-hematologic grade III-IV organ specific toxicity. (Phase II)

OUTLINE:

Nonmyeloablative-conditioning regimen: Patients receive busulfan IV on day -5 and fludarabine IV over 30 minutes on days -4 to -2. Patients undergo total body irradiation on day 0.
Allogeneic peripheral blood stem cell transplantation (PBSC): Patients undergo donor PBSC infusion on day 0.
Graft-versus-host disease prophylaxis: Patients receive oral cyclosporine twice daily on days -3 to 56 followed by a taper to day 180. Patients with a related stem cell donor receive oral mycophenolate mofetil twice daily on days 0-28. Patients with an unrelated stem cell donor receive oral mycophenolate mofetil 3 times daily on days 0-28 followed by a taper twice daily to day 56. Patients with evidence of relapse or persistent disease may also receive up to 3 donor lymphocyte infusions.

PROJECTED ACCRUAL: A total of 225 patients will be accrued for this study; 25 patients accrued into the Phase I and 200 patients into Phase II.