Immunotherapy for Lymphoproliferative Diseases Associated With Epstein-Barr Virus in Patients Who Have Undergone Organ Transplants

OBJECTIVES: I. Examine the toxic effects of allogeneic Epstein-Barr virus (EBV) specific
cytotoxic T lymphocytes (CTL) for the treatment of EBV lymphoproliferative diseases (LPD) in
organ transplant recipients. II. Determine the level of in vivo expansion of allogeneic CTL
and the period of time during which these CTL's can be detected in the blood of recipients
of the T cell infusions.

OUTLINE: Donors undergo leukapheresis, and Epstein-Barr virus (EBV) specific cytoxic T
lymphocytes are cultivated in vitro. Patients receive infusions of EBV specific cytotoxic T
lymphocytes over 5 to 10 minutes on weeks 0, 2, and 4. Patients with stable disease and
those achieving partial remission are followed weekly for signs of disease progression.

PROJECTED ACCRUAL: 10 patients will be accrued in this study.

Inclusion criteria:

- Radiographic evidence of lymphadenopathy or lymphomatous lesions combined with
clinical signs of Epstein-Barr virus lymphoproliferative disease (EBV LPD), such as
fevers and lymphadenopathy

- following an organ transplant Persistent, progressive, or unresponsive disease
despite decreased immunosuppression, chemotherapy, or radiation therapy EBV LPD must
be of host origin

- At least 4 weeks

- Patients serologically hepatitis B and C positive may receive cytotoxic

- T- lymphocytes (CTL) from donors who are serologically positive for the same virus

- Must have an HLA identical or HLA haploidentical donor

Exclusion

- hepatic dysfunction SGOT/SGPT less than 2.5 times upper limit of normal (unless liver
metastases present)

- Bilirubin less than 2.0 mg/dL

- renal dysfunction

- Creatinine clearance at greater than 50 mL/min

- cardiac dysfunction

- neurologic dysfunction

- pulmonary dysfunction

- patients developing EBV LPD who have a donor origin lymphoma

- HIV-1 positive

- Not capable of undergoing leukapheresis