• 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 ]

• Engraftment of HLA-identical peripheral blood stem cell allografts
• Non-relapse mortality at day 100

RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with autologous or syngeneic and allogeneic peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs to kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects of autologous peripheral stem cell transplantation followed by allogeneic peripheral stem cell transplantation and to see how well they work in treating patients with refractory or relapsed lymphoma.

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.

• Graft Versus Host Disease
• Lymphoma

• Drug: carmustine
• Drug: cyclophosphamide
• Drug: cytarabine
• Drug: etoposide
• Drug: melphalan
• Radiation: radiation therapy

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

  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.

DISEASE CHARACTERISTICS:

• Primary Hodgkin's or non-Hodgkin's lymphoma

  • Refractory or relapsed disease after standard chemotherapy
  • At high-risk of relapse with conventional autografting
  • Tumor detectable by radiograph or bone marrow biopsy

• Must have an HLA-identical related donor or, at a minimum, a high likelihood of identifying an HLA-matched unrelated donor

  • Not identical twin
  • Age 12 and over

• Grades 1.0 to 2.1 FHCRC matching allowed for unrelated donors who meet the following criteria:

  • Matched for HLA-A, B, C, DRB1 and DQB1 by high resolution typing
  • Only a single allele disparity will be allowed for HLA-A, B, or C as defined by high resolution typing
• No preexisting donor immunoreactivity that would jeopardize donor hematopoietic cell engraftment as determined by institutional standard practice
• No patient and donor pairs homozygous at a mismatched allele in the graft rejection vector (i.e., two-allele mismatch [the patient is A*0101 and the donor is A*0102])
• G-CSF mobilized PBMC only will be allowed as a hematopoietic stem cell source on this protocol

PATIENT CHARACTERISTICS:

Age:

• 65 and under

Performance status:

• Karnofsky 60-100%

Life expectancy:

• At least 3 months
• No life expectancy severely limited by disease other than lymphoma

Hematopoietic:

• Not specified

Hepatic:

• Not at high risk for veno-occlusive disease of the liver
• Bilirubin no greater than 2.0 mg/dL
• SGOT or SGPT no greater than 2 times normal

Renal:

• Creatinine no greater than 2.0 mg/dL
• Creatinine clearance at least 50 mL/min

Cardiovascular:

• Cardiac ejection fraction at least 45% by MUGA or cardiac echo (for patients with a history of cardiac disease or anthracycline use)
• No poorly controlled hypertension

Pulmonary:

• DLCO at least 50% of predicted

Other:

• HIV negative
• Not pregnant
• Fertile patients must use effective contraception during and for 1 year after study participation
• No donor or centers allowed who will exclusively donate marrow

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior autologous stem cell transplantation using CD34-positive PBSC
• No concurrent growth factors during mycophenolate mofetil administration

Chemotherapy:

• See Disease Characteristics

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 3 months since prior radiotherapy to the mediastinum

Surgery:

• Not specified