Cyclophosphamide, Rituximab, and Either Prednisone or Methylprednisolone in Treating Patients With Lymphoproliferative Disease After Solid 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.

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 central nervous system (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