OBJECTIVES:

• Determine whether stable unrelated peripheral blood stem cell grafts can be safely established using fludarabine, total-body irradiation, and peripheral blood stem cell transplantation with enhanced post-grafting immunosuppression comprising mycophenolate mofetil and cyclosporine in patients with hematologic malignancies or renal cell carcinoma.
• Determine whether the incidence and severity of acute grades II-IV graft-versus-host disease can be reduced in patients with sustained engraftment when treated with mycophenolate mofetil every 8 hours.
• Determine whether engraftment can be maintained in patients with low chimerism and high risk of rejection with a single dose of fludarabine followed by donor lymphocyte infusion while on continued mycophenolate mofetil and cyclosporine.
• Compare disease-free and overall survival in patients treated with this regimen to those treated on protocol FHCRC-1463.00.

OUTLINE: This is a multicenter study.

• Cytoreduction: Patients with advanced malignancies may receive cytoreduction and/or radiotherapy at the discretion of the attending physician and protocol chairperson.
• Conditioning: Patients receive fludarabine IV on days -4 to -2. Patients undergo low-dose total-body irradiation followed by allogeneic peripheral blood stem cell (PBSC) transplantation on day 0.
• Immunosuppression (graft-vs-host disease prophylaxis): Patients receive oral cyclosporine (CSP) twice daily on days -3 to 100 and then tapered to day 177. Patients also receive oral mycophenolate mofetil (MMF) every 8 hours beginning on day 0 (4-6 hours after PBSC transplantation), continuing to day 40, and then tapered off by day 96.
• Donor lymphocyte infusion (DLI): Patients are evaluated for lymphoid and myeloid chimerism on days 28, 56, and 84. Patients without disease progression presenting with low-donor T-cell chimerism (less than 40%), no evidence of graft-versus-host disease requiring therapy, and no active infection revert CSP and MMF doses to their original strength (if tapering has begun) and receive fludarabine IV on day -2 (of DLI). Patients receive DLI on day 0. MMF is continued for 28 days and tapered for 28 days. CSP is continued during MMF therapy and then tapered over 3 months.

Patients are followed weekly until day 90, at 4, 6, 12, 18, and 24 months, and then annually thereafter.

PROJECTED ACCRUAL: A maximum of 150 patients will be accrued for this study within 2 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed metastatic renal cell carcinoma not amenable to surgical cure

  • Clear cell, papillary, or medullary
  • No other solid tumors OR

• Histologically proven hematologic malignancy including, but not limited to, the following:

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

    • Ineligible for autologous hematopoietic stem cell transplantation (HSCT) or failed prior autologous HSCT

  • Low-grade NHL

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

  • Chronic lymphocytic leukemia

    • Failed 2 lines of conventional therapy and refractory to fludarabine

  • Hodgkin's lymphoma

    • Failed front-line therapy

  • Multiple myeloma

    • Prior chemotherapy required
    • Consolidation of chemotherapy by prior autografting allowed

  • Acute myeloid leukemia (AML)

    • Less than 5% blasts at time of transplantation

  • Acute lymphoblastic leukemia

    • Less than 5% blasts at time of transplantation

  • Chronic myelogenous leukemia (CML)

    • Chronic or accelerated phase
    • Patients who have received autografts after high-dose therapy or have undergone intensive chemotherapy with autologous or conventional HSCT for advanced CML are allowed if in complete remission or chronic phase and have less than 5% blasts at time of transplantation

  • Myelodysplastic syndromes (MDS) or myeloproliferative disorders (MPD)

    • Refractory anemia
    • Refractory anemia with ringed sideroblasts
    • Patients with MDS or MPD with transformation to AML must receive cytotoxic chemotherapy and achieve less than 5% blasts at time of transplantation

• Over age 50:

  • Hematologic malignancy treatable by unrelated HSCT

• Age 50 and under:

  • Hematologic disease treatable by allogenic HSCT who, through pre-existing medical conditions or prior therapy, are considered at high risk for regimen-related toxicity associated with or who refuse conventional transplantation
• No rapidly progressive intermediate or high-grade NHL
• No CNS involvement refractory to intrathecal chemotherapy
• No history of brain metastases (for renal cell carcinoma patients)

• Availability of unrelated donor

  • Matched for HLA-DRB1 and DQB1 alleles AND
  • Matched for all serologically recognized HLA-A or B or C antigens and at least 5 of 6 HLA-A or B or C alleles
  • 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 renal cell carcinoma patients)

Life expectancy:

• At least 6 months for renal cell carcinoma patients

Hematopoietic:

• See Disease Characteristics

Hepatic:

• No fulminant liver failure
• No cirrhosis of the liver with portal hypertension
• No alcoholic hepatitis
• No esophageal varices
• No history of bleeding esophageal varices
• No hepatic encephalopathy
• No uncorrectable hepatic synthetic dysfunction evidenced by prolonged 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

Renal:

• Not specified

Cardiovascular:

• No hypertension greater than grade II
• Cardiac ejection fraction at least 35%
• No cardiac failure requiring therapy

Pulmonary:

• DLCO at least 40% and/or receiving supplemental continuous oxygen
• Pulmonary nodules allowed at discretion of principal investigator

Other:

• HIV negative
• Not pregnant or nursing
• Fertile patients must use effective contraception during and for 12 months after study participation
• No fungal infections with radiologically confirmed progression after receipt of amphotericin B or active triazole for more than 1 month
• No vertebral instability for renal cell carcinoma patients

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics

Chemotherapy

• See Disease Characteristics
• Prior hydroxyurea allowed

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• Prior imatinib mesylate allowed
• No other cytoreductive cytotoxic agents within 2 weeks of initiation of conditioning