RATIONALE: Peripheral stem cell or bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy used to kill tumor cells. Sometimes the transplanted cells from a donor can be rejected by the body's normal cells. Mycophenolate mofetil and cyclosporine may prevent this from happening.

PURPOSE: Phase I/II trial to study the effectiveness of radiation therapy and fludarabine followed by donor peripheral stem cell transplantation, mycophenolate mofetil, and cyclosporine in treating patients who have hematologic cancer.

OBJECTIVES:

• Determine the rate of grade III/IV graft-versus-host disease (GVHD) in patients with hematologic malignancies treated with low-dose radiotherapy and fludarabine followed by allogeneic peripheral blood stem cell transplantation, mycophenolate mofetil, and cyclosporine.
• Determine the risk of graft rejection and GVHD in patients treated with this regimen.
• Determine the non-relapse mortality and disease response in patients treated with this regimen.
• Determine the incidence and severity of infectious complications in patients treated with this regimen.

OUTLINE: This is a multicenter study. Patients are assigned to one of two treatment regimens according to disease risk (indolent vs aggressive).

Patients may receive cytoreductive chemotherapy and/or radiotherapy to high-risk sites of bulky disease. All patients then receive conditioning therapy comprising fludarabine IV on days -4 to -2. Patients undergo low-dose total body irradiation followed by unmodified allogeneic peripheral blood stem cell or bone marrow transplantation on day 0. Patients receive oral mycophenolate mofetil (MMF) daily on days 0-27.

Regimen A

• Indolent disease including:

  • Chronic lymphocytic leukemia, chronic myelogenous leukemia (CML) in first chronic phase
  • Acute myeloid leukemia (AML) in first complete remission (CR)
  • Refractory anemia with ringed sideroblasts (RARS)
  • Myeloma in CR or partial remission (PR)
  • Low-grade non-Hodgkin's lymphoma (NHL)
  • Aggressive NHL in first CR Patients receive oral cyclosporine twice daily beginning on day -3. If there is no evidence of graft-versus-host disease (GVHD), cyclosporine is tapered from day 56 until discontinuation by day 180. Beginning at least 2 weeks after completion of cyclosporine, patients with progressive disease receive donor lymphocyte infusion (DLI) IV over 30 minutes for up to 3 infusions. Patients with stable disease may receive DLI at 9-12 months post-transplantation.

Regimen B

• Aggressive disease including:

  • CML in accelerated phase or greater than first CR
  • AML beyond first CR
  • Myelodysplastic syndrome other than RARS
  • Myeloma not in CR/PR
  • Other NHL Patients receive oral cyclosporine twice daily beginning on day -3. If there is no evidence of GVHD, cyclosporine is tapered from day 56 until discontinuation by day 77. Beginning at least 2 weeks after the completion of cyclosporine, patients with persistent disease receive DLI IV over 30 minutes for up to 3 infusions.

Patients are followed at day 84, months 4, 6, 12, 18, and 24, and then annually thereafter.

PROJECTED ACCRUAL: A total of 160 patients (80 per risk group) will be accrued for this study within 3 years.

• Chronic Myeloproliferative Disorders
• Leukemia
• Lymphoma
• Multiple Myeloma and Plasma Cell Neoplasm
• Myelodysplastic Syndromes
• Myelodysplastic/Myeloproliferative Diseases

• Biological: therapeutic allogeneic lymphocytes
• Drug: cyclosporine
• Drug: fludarabine phosphate
• Drug: mycophenolate mofetil
• Procedure: allogeneic bone marrow transplantation
• Procedure: peripheral blood stem cell transplantation
• Radiation: radiation therapy

DISEASE CHARACTERISTICS:

• Over 49 and under 75 years of age with diagnosis of non-Hodgkin's lymphoma (NHL), chronic lymphocytic leukemia (CLL), or multiple myeloma

  • Ineligible for curative autologous peripheral blood stem cell (PBSC) or bone marrow transplantation (BMT) OR
  • Failed prior autologous PBSC or BMT

  • NHL and CLL patients:

    • Failed prior therapy with an alkylating agent and/or fludarabine OR
    • At high risk of relapse

  • Multiple myeloma patients:

    • Stage II or III disease
    • Prior chemotherapy required OR

• Under 50 years of age with diagnosis of NHL, Hodgkin's lymphoma, CLL, or multiple myeloma

  • High risk of regimen-related toxicity due to prior autologous PBSC or BMT or pre-existing medical conditions OR

• Under 75 years of age with diagnosis of other malignant disease amenable to treatment with allogeneic BMT

  • High risk for regimen-related toxicity with standard high-dose regimens due to pre-existing chronic disease of the kidneys, liver, lungs, or heart

  • Including, but not limited to, the following diseases:

    • Myelodysplastic syndromes
    • Myeloproliferative syndromes
    • Acute leukemia with less than 10% blasts in bone marrow
    • Amyloidosis
    • Hodgkin's lymphoma
• Ineligible for high-priority curative autologous PBSC or BMT
• No rapidly progressive aggressive NHL unless in minimal disease state
• No CNS involvement

• Must have genotypically or phenotypically HLA identical related donor that meets all of the following criteria:

  • 12 to 74 years of age
  • Not an identical twin
  • Not pregnant
  • HIV negative
  • No know allergy to filgrastim (G-CSF)
  • No concurrent serious systemic illness

PATIENT CHARACTERISTICS:

Age:

• Under 75

Performance status:

• Karnofsky 50-100%

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Bilirubin no greater than 2 times upper limit of normal (ULN)
• SGPT and SGOT no greater than 4 times ULN

Renal:

• Renal failure allowed
• Creatinine no greater than 2.0 mg/dL

Cardiovascular:

• No poorly controlled hypertension (blood pressure 150/90 or greater while receiving standard medication)
• Ejection fraction at least 40%

Pulmonary:

• No supplementary continuous oxygen
• DLCO at least 30%
• Total lung capacity (TLC) at least 30%
• FEV_1 at least 30%

Other:

• Not pregnant or nursing
• Fertile patients must use effective contraception during and for 12 months after study
• HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Disease Characteristics
• No concurrent growth factors on days 0-27

Chemotherapy:

• See Disease Characteristics

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• Not specified