Cell therapy represents a recent innovation in the treatment of EBV-related malignancies. Limited data on solid-organ transplant recipients have shown regression of disease or decreased levels of EBV DNA after adoptive transfer of autologous EBV-specific CTLs. The immune response analysis in patients affected by infectious mononucleosis has shown that, in vitro, virus-specific CTLs have lytic activity against lymphoblastoid cellular lines transformed by EBV and that CD8+ cells are responsible for the infection control in vitro. Rooney et al73 expanded recipient CTLs by culturing them in vitro with recipient lymphoblastoid cellular lines transformed by EBV. In this way, they obtained EBV-specific CTLs, which, after infusion, blocked the viral replication in vivo. The study of more patients and gene marking procedures of the CTL infused could allow definition of the actual efficacy of these agents and the length of the response in vivo. In the bone marrow transplant setting, lymphoblastoid cell lines can be generated in vitro from the bone marrow of the donor and can provide an effective antigen-presenting cell and a source of viral antigen for generation of EBV-specific CTLs. Moreover, most marrow donors have a strong immune response against EBV.74 Several clinical studies show that T-cell infusions can control life-threatening PTLDs in bone marrow transplant patients where the bone marrow donor is healthy and available to donate a blood sample. In one study,75 5 patients with EBV-positive PTLDs, arising after allogeneic T-cell–depleted bone marrow transplantation, received peripheral blood mononuclear cell infusions from their EBV-seropositive marrow donors. Infusions were well tolerated and caused lymphoma regression; however, all recipients experienced severe graft-vs-host disease. Therefore, alloreactive T cells must be removed from peripheral blood mononuclear cells to achieve complete tumor and virus specificity.75 To determine whether adoptive transfer of donor-derived EBV-specific CTLs can restore the immune response to EBV and prevent EBV lymphoma, Heslop et al74 administered EBV-specific CTL lines containing gene-marked CD4 and CD8 cells to 14 bone marrow transplant patients. This study showed that transferred T cells not only restored the patients' immune response to EBV but also persisted for as long as 18 months, saving their ability to respond to viral stimulation in vivo. Even if the use of a marker gene allows demonstration of the longevity of infused T cells and their retention of EBV reactivity, it does not permit an estimate of the contribution from endogenous EBV-specific T cells.74 Further studies have demonstrated that EBV-specific CTLs grown from donor bone marrow can be used to prevent and treat PTLDs after bone marrow transplantation. Rooney et al76 infused 39 bone marrow recipients with 2 to 4 doses of EBV-specific polyclonal (CD4+ and CD8+) T-cell lines grown in vitro from the bone marrow donors. The prophylactic CTL infusions were administered a median of 3 months after transplantation. Six recipients had high levels of EBV DNA in peripheral blood before CTL infusion, which decreased within 2 to 3 weeks of treatment. None of the patients developed PTLDs during follow-up, whereas historical controls who did not receive CTL prophylaxis had a tumor incidence of 11%.