Immune Therapy in Treating Patients with Epstein-Barr Virus Lymphoproliferative Disorders or Epstein-Barr Virus-Associated Malignancies

Inclusion Criteria

• Pathologically documented EBV antigen positive lymphoproliferative disease, lymphoma or other EBV-associated malignancy, OR
• Evaluable disease as demonstrated by clinical and/or radiologic studies with current or prior elevated blood levels of EBV-deoxyribonucleic acid (DNA) exceeding 500 copies/ml by quantitative real time polymerase chain reaction (PCR), OR
• Persistent or recurrent elevations in levels of EBVDNA exceeding 500 copies/ml in patients previously treated for EBV lymphoproliferative disease (EBVLPD) with chemotherapy and/or Rituxan who do not yet have clinically or radiologically evaluable disease but are at high risk of disease recurrence
• EBV-specific T-cells from donor of the patient's transplant are not available
• EBV-specific T-cells are available for adoptive immune cell therapy from a consenting third party donor; the third party EBV CTLs to be administered will be selected on the basis of two criteria: 1) that they are matched for at least 2 HLA antigens and 2) that they are restricted by an allele shared with the EBV+ malignancy (if known), or with the donor in HSCT recipients, or patient in organ transplant or immunodeficient patients
• Karnofsky performance status (KPS) or Lansky score >= 20
• A life expectancy of at least 6 weeks
• Absolute neutrophil count (ANC) >= 1 K/mcL, with or without filgrastim (GCSF) support
• Platelets >= 20 K/mcL
• Creatinine =< 2.0 mg/dl
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST) < 3.0 x the institutional upper limit of normal (ULN)
• Total bilirubin < 2.5 x the institutional ULN
• Stable blood pressure and circulation not requiring pressor transport
• Adequate cardiac function as demonstrated by electrocardiogram (EKG) and/or echocardiographic evidence (may be performed within 30 days prior to treatment)
• However, abnormalities of specific organs will not be considered grounds for exclusion if they are the result of the EBV+ malignancy or its treatment (e.g. a renal allograft recipient with an EBVLPD may be on dialysis because the allograft was rejected when the immune suppression was stopped as a first approach to treatment of the EBVLPD); a the discretion of the investigator, patients with elevated but stable creatinine will not be precluded from treatment on study
• It is expected that five types of patients afflicted with EBV-associated lymphomas, lymphoproliferative disease or malignancies will be referred and will consent to participate in this trial; these are:
• Patients developing EBV lymphomas or lymphoproliferative disorders following an allogeneic hematopoietic progenitor stem cell transplant (HSCT) (ie: marrow, peripheral blood stem cell [PBSC], or umbilical cord blood); in these cases, the HSCT donor, if EBV-seropositive, will be used as the donor of EBV-specific T-cells for adoptive immunotherapy wherever possible, because the EBV-LPD are almost invariably derived from that marrow donor; these patients will be enrolled onto protocol Institutional Review Board (IRB) # 95-024; however, if the HSCT donor is EBV seronegative or not readily available (e.g. a cord blood transplant), the patient will be a candidate to receive EBV-specific T-cells generated from a third party seropositive donor that have been generated and stored in the Memorial Sloan Kettering Cancer Center (MSKCC) bank of cryopreserved immune T-cells for adoptive cell therapy; for these patients, the third party donor derived T cells to be used will be selected primarily on the basis of 1) matching for, at least, 2 HLA antigens and 2) one restricted allele shared by the transplant donor and recipient; however, priority is given to T cells partially HLA antigen matched with, and restricted by, HLA alleles of the transplant donor, since EBV + lymphomas in HSCT recipients are usually (but not always) derived from the transplant donors' cells
• Patients developing EBV lymphomas or lymphoproliferative disorders following an allogeneic organ transplant; in these cases, the lymphoma is usually of recipient origin; EBV-specific T-cells will be selected from the MSKCC bank expanded from an EBV-seropositive normal donor who is at least matched for 1) 2 HLA antigens and 2) one restricted allele with the EBV lymphoma; if the origin of the lymphoma is unknown, T-cells partially matched with the recipient transplant will be used, since these lymphomas are usually of host origin; using this approach to donor selection, it is expected that the EBV-specific, HLA restricted cytotoxic T-cells expanded from the HLA partially-matched donor would be able to recognize and kill lymphoma cells presenting EBV antigens in the context of an appropriate HLA restricting element; priority will be given to the use of partially matched EBV specific T cells known to be restricted by an HLA allele shared by the lymphoma (or, if known, the patient)
• Patients with acquired immunodeficiency syndrome (AIDS) developing EBV lymphomas or lymphoproliferative diseases as a consequence of the profound acquired immunodeficiency induced by human immunodeficiency virus (HIV); for such patients, EBV specific T-cells from third party seropositive donors who are HLA compatible in 1) at least 2 HLA antigens and 2) one restricted allele shared by the patient will be used; selection of T cells known to be restricted by an HLA allele shared by the patient will be given priority
• Patients who develop EBV lymphomas or lymphoproliferative diseases or other EBV-associated malignancy as a consequence of profound immunodeficiencies associated with a congenital immune deficit or acquired as a sequela of anti-neoplastic or immunosuppressive therapy; for these patients, normal, EBV specific T-cells from third party seropositive donors who are HLA compatible in 1) at least 2 HLA antigens and 2) one restricted allele shared by the patient will be used; again, selection of T cells known to be restricted by an allele shared by the patient will be given priority
• Patients who develop other EBV-associated malignancies without pre-existing immune deficiency, including: EBV+ Hodgkin's and non-Hodgkin's disease, EBV+ nasopharyngeal carcinoma, EBV+ hemophagocytic lymphohistiocytosis, or EBV+ leiomyosarcoma; normal, EBV specific T-cells from third party seropositive donors who are HLA compatible in 1) at least 2 HLA antigens and 2) one restricted allele shared by the patient will be used; again, selection of T cells known to be restricted by an HLA allele shared by the patient will be given priority
• DONORS: Donors in groups 1 and 2 would have already been determined to be eligible and will have donated blood or leukocytes to establish EBV-specific T-cells under IRB # 05-065, 07-055, 95-024, or 12-086; there are no additional eligibility requirements for these donors
• DONORS: Donors in group 3, however, will need to meet the following eligibility requirements prior to donation: * Donors must satisfy the criteria specified in Food and Drug Administration (FDA) 21 Code of Federal Regulations (CFR) 1271 * Donors must be typed for HLA-A, B, C, and DR * Donors must have a hemoglobin value > 10 g/dl * Donors must be capable of undergoing, at least, a single standard 2 blood volume leukapheresis or a donation of one unit of whole blood

Exclusion Criteria

• Patients with active (grade 2-4) acute graft vs. host disease (GVHD), chronic GVHD or an overt autoimmune disease (e.g. hemolytic anemia) requiring high doses of glucocorticosteroid (> 0.5 mg/kg/day prednisone or its equivalent) as treatment
• Patients who are pregnant
• Patients with severe comorbidities, not related to their EBV-associated malignancy, that would be expected to preclude their survival for the 6 weeks required to assess response of T cell therapy
• DONOR: Human T-lymphotropic virus (HTLV)/HIV(+) or hepatitis B or C antigen(+) donors
• DONOR: Known EBV seronegative