Safety of allogeneic Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes for patients with refractory EBV-related lymphoma.

Abstract

Epstein-Barr virus (EBV) causes lymphomas in immunocompromised individuals such as recipients of stem cell or organ transplants and patients with acquired immunodeficiency syndrome (AIDS). EBV has also been detected in the Reed-Sternberg cells of approximately 50% of all cases of Hodgkin's disease (HD). The purpose of this study was to examine the safety, and the clinical and immunological effects of infusing allogeneic EBV-specific cytotoxic T lymphocytes (CTL) for patients with refractory EBV-positive malignancies. In this pilot study, we have treated four patients with EBV-related lymphoma using allogeneic EBV-specific CTL. Two patients received EBV-specific CTL derived from partially human leucocyte antigen (HLA)-matched donors and the other two from HLA-matched siblings. No complications were observed as a result of the CTL infusions and all patients showed increased levels of EBV-specific CTL precursors (CTLp) post infusion. Of the two organ transplant patients, one had refractory disease and has sustained a complete remission following the T-cell infusions. The second has also been disease free since T-cell infusions, although the efficacy cannot be definitively attributed to CTL therapy because this patient received local radiation therapy prior to immunotherapy. A patient with AIDS-related, EBV-positive lymphoma had disease progression following CTL infusions. One HD patient received HLA 4/6 matched T cells from an unrelated donor and showed a decrease in the size of affected lymph nodes and resolution of B-symptoms post infusion. In conclusion, adoptive immunotherapy with allogeneic EBV-specific CTL is safe and may have efficacy in patients with high-risk or refractory EBV-related tumours.