RATIONALE: Drugs used in chemotherapy such as cyclophosphamide, prednisone, and methylprednisolone use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Combining cyclophosphamide and either prednisone or methylprednisolone with rituximab may be effective in treating lymphoproliferative disease following organ transplantation.

PURPOSE: Phase II trial to study the effectiveness of combining cyclophosphamide and either prednisone or methylprednisolone with rituximab in treating patients who have Epstein-Barr virus-positive lymphoproliferative disease following organ transplantation.

OBJECTIVES:

• Determine the safety and toxicity of cyclophosphamide, rituximab, and prednisone or methylprednisolone in patients with CD20-positive and Epstein-Barr virus-positive post-transplant lymphoproliferative disease (PTLD) after solid organ transplantation.
• Determine the 2-year event-free survival, defined as alive and in continuous complete remission with a functioning original allograft, of patients treated with this regimen.
• Determine the response rate in patients treated with this regimen.
• Determine the PTLD gene expression profile by microarray analysis and fluorescent in situ hybridization in patients treated with this regimen.
• Determine the accrual rate of patients to this study.

OUTLINE: This is a multicenter study.

Patients receive cyclophosphamide IV over 30-60 minutes on day 1 and oral prednisone or methylprednisolone IV twice daily on days 1-5. During courses 1 and 2 only, patients also receive rituximab IV over 2-5 hours on days 1, 8, and 15. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression, a new primary or secondary malignancy, or unrelated disease.

After finishing study treatment, patients are followed periodically for at least 5 years.

PROJECTED ACCRUAL: A total of 60 patients (50 with non-fulminant post-transplant lymphoproliferative disease [PTLD] and 10 fulminant PTLD) will be accrued for this study within 2.5-3 years.

• Biological: rituximab
• Drug: cyclophosphamide
• Drug: methylprednisolone
• Drug: prednisone

DISEASE CHARACTERISTICS:

• Histologically confirmed post-transplant lymphoproliferative disease (PTLD)

  • Presents with 1 of the following:

    • Fulminant PTLD (F-PTLD)

      • Fever greater than 38°C
      • Hypotensive (for age)

      • Evidence of multiple organ involvement/failure, including at least 2 of the following:

        • Marrow (including pancytopenia without detectable B-cell proliferation)
        • Liver (coagulopathy, transaminitis, and/or hyperbilirubinemia)
        • Lungs (interstitial pneumonitis with or without pleural effusions)
        • Gastrointestinal tract hemorrhage

    • Non-fulminant PTLD (NF-PTLD)

      • Does not meet the above F-PTLD criteria
      • Considered medically refractory to reduced immune suppression (50% or more reduction of immunosuppression) for at least 1 week
• CD20 positive AND Epstein-Barr virus positive
• Must have received prior solid organ transplantation
• Must have residual disease after biopsy and/or surgery
• No PTLD CNS disease, defined as positive cytology and/or radiographic evidence

PATIENT CHARACTERISTICS:

Age

• Under 31

Performance status

• Not specified

Life expectancy

• NF-PTLD patients:

  • At least 8 weeks

Hematopoietic

• See Disease Characteristics

Hepatic

• See Disease Characteristics

Renal

• Not specified

Pulmonary

• See Disease Characteristics

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy

• More than 1 month since prior rituximab

Chemotherapy

• More than 4 weeks since prior chemotherapy and recovered

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• See Disease Characteristics