This study is a trial of Epstein Barr virus-specific CTLs in immunocompromised patients with Epstein Barr virus-associated malignancies. Individuals who are chronically immunocompromised such as patients with HIV infection, recipients of bone marrow or solid organ transplants, and patients with congenital immunodeficiencies have in common a predisposition to develop EBV-associated lymphoproliferative disease including lymphoma. In the absence of an effective cytotoxic T cell response, a trait these immunocompromised patients all share, the virus brings about uncontrolled proliferation of B lymphocytes. Reconstituting the immune system may cause regression of the lymphoma. Patients treated with EBV-specific cytotoxic T lymphocytes expanded from bone marrow donors have achieved remissions and such infusions are now being carried out prophylactically in high risk patients. Early trials with virus specific lines or clones have had in common the apparent absence of toxicity. However, all trials to date have been carried out in patients who were HLA matched with the donor of the lymphocytes. In vitro studies sugest that cytotoxic T cell lines should also be effective and specific in the haploidentical setting. The purpose of thi study is to demonstrate that their is no clinically significant non-specific targeting of EBV-specific cytotoxic T cell infusions in HLA haplo- identical immunocompromised patients with EBV-associated malignancies. Specifically to demonstrate that the incidence of severe graft versus host disease is substantially different from the 100% incidence that would be anticipated if unmanipulated buffy coat from haploidentical donors were used. To date, two adult patients have been treated with the EBV-specific CTLs. No toxicity was seen. These patients both had a post-transplant lymphoma and were treated with the CTLs after they received conventional chemotherapy. No toxicity was seen. Assays to evaluate the half life of the infused cells will be run at a later date. Because of the increased risk of post transplant lymphoproliferative disorder in children who receive living related liver transplants, the EBV-specific CTLs are being prepared in advance in this population. Normally it takes at least eight weeks to prepare the CTLs. The donors of two patients have been pheresed, a necessary step to prepare the cells. No children have yet received the cells.
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