OBJECTIVES:

Primary

• Determine whether the incidence of life-threatening graft-versus-host disease (GVHD) can be reduced after unrelated donor peripheral blood mononuclear cell hematopoietic stem cell transplantation using nonmyeloablative conditioning with truncated cyclosporine and prolonged administration of mycophenolate mofetil in patients with hematologic malignancies or metastatic renal cell carcinoma.

Secondary

• Compare the incidence of acute and chronic GVHD in patients treated with this regimen vs patients treated on protocols FHCRC-1463.00 and FHCRC-1641.00.
• Compare the utilization of corticosteroids in patients treated with this regimen vs patients treated on protocols FHCRC-1463.00 and FHCRC-1641.00.
• Compare the survival of patients treated with this regimen vs patients treated on protocols FHCRC-1463.00 and FHCRC-1641.00.

OUTLINE: This is a multicenter study.

• Conditioning regimen: Patients receive fludarabine IV over 30 minutes on days -4 to -2 and low-dose total body irradiation (TBI) on day 0.
• Allogeneic hematopoietic stem cell transplantation (HSCT): After the completion of TBI, patients undergo allogeneic HSCT on day 0.
• Immunosuppression: Patients receive oral cyclosporine twice daily on days -3 to 80 in the absence of acute graft-versus-host disease (GVHD). Patients also receive oral mycophenolate mofetil (MMF) 3 times daily on days 0-29 and then, in the absence of GVHD, twice daily on days 30-149. MMF is tapered beginning on day 150 and continuing until day 180.

Patients are followed at 6 months, 12 months, 18 months, and 24 months and then annually for 5 years after HSCT.

PROJECTED ACCRUAL: A total of 70 patients will be accrued for this study within 1.5 years.

DISEASE CHARACTERISTICS:

• Diagnosis of either of the following:

  • Hematologic malignancy

    • Meeting 1 of the following criteria:

      • Over 50 years of age with a hematologic malignancy treatable by unrelated hematopoietic stem cell transplantation (HSCT) = 50 years of age and under with a hematologic malignancy treatable by allogeneic HSCT and considered to be at high risk for regimen-related toxicity associated with a conventional transplantation (greater than 40% risk of transplant-related mortality) due to a preexisting medical condition or prior therapy OR refused a conventional HSCT

    • Including, but not limited to the following:

      • Intermediate- or high-grade non-Hodgkin's lymphoma (NHL)

        • Not eligible for autologous HSCT or failed autologous HSCT

      • Low-grade NHL

        • Less than 6 months duration of complete remission (CR) between courses of conventional therapy

      • Chronic lymphocytic leukemia

        • Refractory to fludarabine

      • Hodgkin's lymphoma

        • Failed prior front-line therapy

      • Multiple myeloma

        • Received prior chemotherapy (consolidation of chemotherapy by autografting prior to nonmyeloablative HSCT is allowed)

      • Acute myeloid leukemia (AML)

        • Less than 5% marrow blasts at the time of transplantation

      • Acute lymphoblastic leukemia

        • Less than 5% marrow blasts at the time of transplantation

      • Chronic myelogenous leukemia (CML)

        • Chronic phase or accelerated phase
        • Prior autografts after high-dose therapy OR prior intensive chemotherapy with filgrastim (G-CSF)-mobilized peripheral blood mononuclear cell autologous or conventional HSCT for advanced CML allowed provided disease is in CR or chronic phase and there are less than 5% marrow blasts at the time of transplantation

      • Myelodysplastic syndromes (MDS) or myeloproliferative disorder

        • Refractory anemia (RA)
        • RA with ringed sideroblasts
        • Patients with greater than 5% marrow blasts (including those with transformation to AML) must receive cytotoxic chemotherapy and achieve less than 5% marrow blasts at the time of transplantation

  • Metastatic renal cell carcinoma (RCC) not amenable to surgical cure OR history of or active histologically or radiologically confirmed metastatic disease, including 1 of the following histological types:

    • Clear cell
    • Papillary
    • Medullary
• No rapidly progressive intermediate- or high-grade NHL
• No history of brain metastases (RCC patients)
• No CNS involvement with disease refractory to intrathecal chemotherapy
• No other non-hematological tumors except RCC

• Available unrelated donor

  • Matched for HLA-A, B, C, DRB1, and DQB1
  • Only a single allele disparity is allowed for HLA-A, B, or C
  • No positive anti-donor cytotoxic crossmatch
  • No patient and donor pairs homozygous at a mismatched allele in the graft rejection vector
  • No marrow donors NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS:

Age

• See Disease Characteristics
• Any age

Performance status

• Karnofsky 60-100% (70-100% for RCC patients)

Life expectancy

• At least 6 months (RCC patients)

Hematopoietic

• Not specified

Hepatic

• No fulminant liver failure
• No cirrhosis of the liver with evidence of portal hypertension
• No alcoholic hepatitis
• No hepatic encephalopathy
• No uncorrectable hepatic synthetic dysfunction evidenced by prolongation of the PT
• No ascites related to portal hypertension
• No bacterial or fungal liver abscess
• No biliary obstruction
• No chronic viral hepatitis with bilirubin greater than 3 mg/dL
• No symptomatic biliary disease
• No esophageal varices
• No history of bleeding esophageal varices

Renal

• Not specified

Cardiovascular

• Cardiac ejection fraction at least 35%*
• No hypertension greater than grade II NOTE: *Ejection fraction required for patients with a history of anthracycline exposure or cardiac disease

Pulmonary

• DLCO at least 40%
• No requirement for continuous supplementary oxygen
• Pulmonary nodules allowed provided study enrollment is approved by the principal investigator

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception during and for 1 year after study participation
• HIV negative
• No fungal infection with radiological progression after prior amphotericin B or active triazole therapy for more than 1 month
• No vertebral instability (RCC patients)

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics
• Prior cytokine therapy allowed
• Prior rituximab allowed
• No concurrent growth factors for 1 month after HSCT

Chemotherapy

• See Disease Characteristics
• More than 2 weeks since prior intensive chemotherapy, excluding low-dose cytarabine and chlorambucil

Endocrine therapy

• Not specified

Radiotherapy

• Prior radiotherapy for advanced malignancy or to reduce tumor bulk allowed

Surgery

• Not specified

Other

• More than 2 weeks since prior cytotoxic agents for cytoreduction, excluding hydroxyurea and imatinib mesylate