OBJECTIVES:

• Compare the 1-year overall survival rate of patients with relapsed low-grade non-Hodgkin's lymphoma or chronic lymphocytic leukemia treated with fludarabine and total body irradiation vs cyclophosphamide and fludarabine followed by allogeneic peripheral blood stem cell transplantation and donor lymphocyte infusions.
• Compare the toxic effects of these regimens in these patients.
• Compare the incidence and severity of acute and chronic graft-versus-host disease in patients treated with these regimens.
• Compare the 1-year treatment-related mortality and infectious complications in patients treated with these regimens.
• Compare the efficacy of these treatment regimens, in terms of 1-year disease-free survival, of these patients.
• Compare the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to disease, age (less than 55 vs over 55), and participating transplantation center. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive fludarabine IV on days -4 to -2. Patients undergo total body irradiation followed by allogeneic peripheral blood stem cell transplantation (PBSCT) on day 0. Patients receive graft-versus-host disease (GVHD) prophylaxis comprising oral cyclosporine twice daily on days -2 to 90 followed by a taper on days 90-150 and oral mycophenolate mofetil twice daily on days 0-28.
• Arm II: Patients receive fludarabine IV on days -6 to -2 and cyclophosphamide IV on days -3 to -2. Patients undergo PBSCT on day 0. Patients receive GVHD prophylaxis comprising methotrexate IV on days 1, 3, 6, and 11 and tacrolimus IV continuously and then orally on days -2 to 90 followed by a taper on days 90-150.

At approximately day 180, patients with persistent disease, evidence of T-cell chimerism, and no GVHD may receive up to 3 donor lymphocyte infusions administered every 1-2 months.

Quality of life is assessed at baseline, 1 month, every 3 months for 1 year, and then every 6 months for 1 year.

Patients are followed at 1 month, every 3 months for 1 year, and then annually for 2 years.

PROJECTED ACCRUAL: A total of 100 patients (50 per treatment arm) will be accrued for this study.

DISEASE CHARACTERISTICS:

• Diagnosis of chronic lymphocytic leukemia OR

• Diagnosis of non-Hodgkin's lymphoma

  • Lymphoplasmacytic lymphoma
  • Grade I follicular small cleaved cell lymphoma
  • Grade II follicular mixed cell lymphoma
  • Diffuse small cleaved cell lymphoma
  • Small lymphocytic lymphoma
• Relapsed after at least 1 course of prior therapy
• Availability of a 6/6 HLA A, B, and DR identical sibling donor
• Nonmyeloablative transplantation candidate
• No clinically significant effusions or ascites that would preclude administration of methotrexate

PATIENT CHARACTERISTICS:

Age:

• 18 to 75

Performance status:

• ECOG 0-2 OR
• Zubrod 0-2

Life expectancy:

• At least 6 months

Hematopoietic:

• Not specified

Hepatic:

• Bilirubin no greater than 3 mg/dL

Renal:

• Creatinine no greater than 2 mg/dL

Cardiovascular:

• LVEF at least 40% on MUGA scan or echocardiogram

Pulmonary:

• DLCO at least 50% of predicted

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No uncontrolled bacterial, viral, fungal, or parasitic infection
• HIV1 and HIV2 negative
• No other active malignancy except basal cell skin cancer
• No recent history of drug or alcohol abuse
• No other primary disease or comorbid illness that would severely limit life expectancy

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Disease Characteristics
• Prior autologous bone marrow transplantation allowed if disease has progressed after transplantation
• No entry on study as part of a tandem autologous transplantation followed by nonmyeloablative allograft protocol

Chemotherapy:

• Not specified

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• Not specified