• Maximum tolerated dose [ Designated as safety issue: Yes ]
  
• Safety and toxicity [ Designated as safety issue: Yes ]
  
• Survival of LMP-specific cytotoxic T-lymphocytes [ Designated as safety issue: No ]
  
• Immunological efficacy and antitumor activity [ Designated as safety issue: No ]
  

OBJECTIVES:

• To determine the safety of autologous or allogeneic LMP-specific cytotoxic T-lymphocytes (CTL) in patients with Epstein-Barr virus (EBV)-positive lymphoma, lymphoepithelioma, or severe chronic active EBV infection syndrome.
• To determine the survival and immune function of LMP-specific CTL.
• To assess the antiviral and antitumor effects of LMP-specific CTL.
• To obtain preliminary information on the safety of and response to an extended dosage regimen.

OUTLINE: This is a dose-escalation study. Patients are stratified according disease status (relapsed lymphoma/lymphoepithelioma or at high risk for relapse vs in remission or has minimal residual disease after autologous or syngeneic stem cell transplantation vs in remission or has detectable disease after allogeneic stem cell transplantation).

Peripheral blood mononuclear cells (PBMC) are collected from the patient or a donor for generation of LMP-specific cytotoxic T-lymphocytes (CTL). PBMC are stimulated with antigen-presenting cells (APC) expressing LMP1/2 antigen and expanded with aldesleukin.

Patients receive autologous or allogeneic LMP-specific CTLs IV over 1-10 minutes on days 0 and 14. Patients are evaluated at 8 weeks. Patients with stable disease or a partial response may receive 6 additional doses of CTLs once a month.

After completion of study treatment, patients are followed at 3, 6, 9, and 12 months and then annually for 5 years.

DISEASE CHARACTERISTICS:

• Diagnosis of any of the following:

  • Epstein-Barr virus (EBV)-positive Hodgkin or non-Hodgkin lymphoma
  • Lymphoepithelioma of any histological subtype
  • EBV (associated)-T/NK-lymphoproliferative disease

  • Severe chronic active EBV infection syndrome (SCAEBV)

    • SCAEBV is defined as a high EBV viral load in plasma or peripheral blood mononuclear cells (PBMC) (> 4,000 genomes/ug PBMC DNA) and/or biopsy tissue positive for EBV

• Meets 1 of the following criteria:

  • In second or subsequent relapse (or in first relapse or has active disease, if immunosuppressive chemotherapy contraindicated, or disease relapsed multiple times and is currently in remission but has a high risk of relapse) OR has primary disease or in first remission, if immunosuppressive chemotherapy is contraindicated, (e.g., developed Hodgkin lymphoma after solid organ transplantation) or if the lymphoma is a second malignancy (e.g., Richter transformation of chronic lymphocytic leukemia)
  • In remission or has minimal residual disease after autologous or syngeneic stem cell transplantation (SCT)
  • In remission or has detectable disease after allogeneic SCT
• At least 50% donor chimerism in either peripheral blood or bone marrow (for patients who have undergone prior allogeneic SCT)

PATIENT CHARACTERISTICS:

• Karnofsky performance status (PS) OR Lansky PS 50-100%
• Life expectancy ≥ 6 weeks
• Hemoglobin > 8.0 g/dL
• Prothrombin time normal
• Bilirubin ≤ 3 times normal
• AST ≤ 5 times normal
• Creatinine ≤ 2 times normal for age
• Not pregnant
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative
• No concurrent severe infection
• No grade III-IV graft-vs-host disease

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• More than 1 month since prior investigational therapy