USE OF GENE-MODIFIED VIRUS-SPECIFIC T-LYMPHOCYTES TO CONTROL EPSTEIN-BARR-VIRUS-RELATED LYMPHOPROLIFERATION

Reactivation of Epstein-Barr virus (EBV) after bone-marrow transplanta tion leads in many cases to lymphoproliferative disease that responds poorly to standard therapy and is usually fatal. To prevent or central this complication, we prepared EBV-specific cytotoxic T-lymphocyte (C TL) lines from donor leucocytes and infused them into ten allograft re cipients. Three of the patients had shown signs of EBV reactivation, w ith or without overt lymphoproliferation, and the others received CTL infusions as prophylaxis. No patient developed any complication that c ould be attributed to the CTL infusions. in the three patients with EB V reactivation, EBV DNA concentrations (measured by semiquantitative p olymerase chain reaction [PCR]), which had increased 1000-fold or more , returned to the control range within 3-4 weeks of immunotherapy. The most striking consequence was the resolution of immunoblastic lymphom a in a 17-year-old patient who received four CTL infusions (two 1x10(7 )/m(2) and two 5x10(7)/m(2)). Because the CTL had been genetically mar ked before infusion, we were able to show by PCR analysis that they pe rsisted for 10 weeks after administration. EBV-specific donor-type T-c ell lines seem to offer safe and effective therapy for control of EBV- associated lymphoproliferation.