• Engraftment of HLA-identical peripheral blood stem cell allografts [ Designated as safety issue: No ]
  
• Non-relapse mortality at day 100 [ Designated as safety issue: Yes ]
  

OBJECTIVES:

Primary

• Assess engraftment of HLA-identical peripheral blood stem cell (PBSC) allografts given after conditioning with total body irradiation with or without fludarabine and postgrafting immunosuppression with cyclosporine and mycophenolate mofetil in patients with refractory or relapsed lymphoma treated with initial autologous PBSC transplantation.
• Determine nonrelapsed mortality at day 100 in patients treated with this regimen.

Secondary

• Determine disease-free and overall survival of patients treated with this regimen.

OUTLINE: This is a multicenter study. Patients are stratified according to response to prior chemotherapy (sensitive vs resistant).

Patients who do not have autologous peripheral blood stem cells (PBSC) stored receive mobilization on another protocol, then have PBSC collected and stored. Patients then proceed to conditioning and transplantation.

Patients may receive one of two conditioning regimens.

• Regimen 1: Patients receive cyclophosphamide IV on days -6 and -5 followed by total body irradiation (TBI) twice a day on days -3 to -1.

• Regimen 2: Patients receive carmustine IV over 3 hours on day -7, etoposide IV over 2 hours and cytarabine IV over 3 hours twice a day on days -6 to

  • 3, and melphalan IV over 30 minutes on day -2. After completion of conditioning therapy, all patients undergo reinfusion of autologous PBSC or syngeneic PBSC on day 0. Some patients may receive involved field irradiation to bulky disease after autologous PBSC reinfusion or syngeneic PBSC and before nonmyeloablative allograft.

Within 40-120 days after autologous or syngeneic PBSC transplantation, patients proceed to nonmyeloablative allograft. Cyclosporine administered orally twice daily on days -3 to 56 or days -3 to 100, then tapered until day 180. Some patients receive fludarabine IV over 30 minutes on days -4, -3, and -2.

TBI is administered on day 0 followed by allogeneic PBSC infusion. Patients also receive oral mycophenolate mofetil twice a day beginning on day 0 and continuing until day 27 or three times a day or twice a day beginning on day 0 and continuing until day 28, then tapered on day 40 and discontinued after day 96.

Based on day 56 disease status, patients may receive donor lymphocyte infusion (DLI) if there is evidence of disease progression and no evidence of graft-vs-host disease. DLI may be repeated every 65 days for up to 4 doses.

Patients are followed weekly for 3 months, at 4 and 6 months, every 6 months for 2 years, and then annually until 5 years after transplantation.

PROJECTED ACCRUAL: A total of 110 patients will be accrued for this study within 11 years.