A lot of patients with Hodgkin disease or non-Hodgkin Lymphoma show evidence of infection with the virus that causes infectious mononucleosis Epstein Barr virus (EBV) before or at the time of their diagnosis of Lymphoma. EBV is often found in the cancer cells suggesting that it may play a role in causing Lymphoma. The cancer cells infected by EBV are very clever because they are able to hide from the body's immune system and escape destruction. We want to see if we can grow special white blood cells, called T cells, that have been trained to kill EBV infected cells and give them back to the patient.

The purpose of this study is to find the largest safe dose of EBV specific cytotoxic T lymphocytes, to learn what the side effects are and to see whether this therapy might help patients with Hodgkin disease and non-Hodgkin Lymphoma.

We will take 60-70 ml (12 teaspoonfuls) of blood from the patient. We will first make a B cell line called a lymphoblastoid cell line or LCL by infecting this blood with a laboratory strain of EBV called B95. We will then use this EBV infected cell line (which have been treated with radiation so that they cannot grow) as stimulator cells and mix it with more blood. This stimulation will train the T cells to kill EBV infected cells and result in the growth of an EBV specific T cell line. We will then test the T cells to make sure that they kill the EBV infected cells and not the normal cells and freeze them.

The cells will be thawed and injected into the patients vein (IV) over 10 minutes, after pretreatment with Tylenol and Benadryl. A total of two doses will be given two weeks apart. All of the treatments will be given at Texas Children's Hospital or The Methodist Hospital.

We will follow the patient in the clinic after the injections. To learn more about the way the T cells are working and how long they last in the body, an extra 20-40 mls (4-8 teaspoonfuls) of blood will be taken before each infusion and then 24 hours after each infusion, 3-4 days after each infusion and then weekly for 2 weeks after each infusion (total of 9 times). After this, blood will be taken every 3 months for 1 year.

• Hodgkin Disease
• Non-Hodgkins Lymphoma

Eligibility Criteria:

• All patients with Hodgkin disease or non-Hodgkin lymphoma who have received a bone marrow transplant and in whom in the EBV genome or antigens have been demonstrated in tissue biopsies will be eligible for this trial regardless of the histological subtype of their disease.
• Any patient with Hodgkin disease, containing the EBV genome or antigen, receiving a bone marrow transplant regardless of age or sex.
• Patients with a life expectancy > 6 weeks.
• Patients with a Karnofsky score of > 50.
• Patient, parent/guardian able to give informed consent.
• Patients with bilirubin < 2x normal, SGOT < 3x normal, and Hgb > 8.0.
• Patients with a creatinine < 2x normal for age or creatinine clearance > 2x normal for age.
• Patients with an ANC > 500mm
• No severe intercurrent infection.
• Patients should have been off other investigational therapy for one month prior to entry in this study.

Exclusion Criteria:

• Patients with a life expectancy of <6 weeks.
• Patients with an EBV positive lymphoma secondary to an acquired or congenital immunodeficiency.
• Patients with a Karnofsky score of < 50.
• Patients with a severe intercurrent infection.
• Patients with a bilirubin > 2x normal. SGOT > 3x normal or abnormal prothrombin time.
• Patients with a creatinine > 2x normal for age or creatinine clearance < 2x normal for age.
• Patients with an ANC < 500mm
• Patient, parent/guardian unable to give informed consent.
• Due to unknown effects of this therapy on a fetus, pregnant women are excluded from this research. Women of childbearing potential must be on appropriate birth control for the duration of the study and 6 months after completion of the study. The male partner should wear a condom.

• The Methodist Hospital System
• Texas Children's Hospital
• Center for Cell and Gene Therapy