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