Adoptive immunotherapy with allogeneic Epstein–Barr virus (EBV)‐specific cytotoxic T‐lymphocytes for recurrent, EBV‐positive Hodgkin disease

BACKGROUND It has been shown that adoptive immunotherapy with Epstein–Barr virus (EBV)‐specific cytotoxic T‐lymphocytes (CTL) is effective for the treatment of EBV‐induced lymphoproliferative disease in stem cell transplantation recipients and organ transplantation recipients. The role of EBV CTL in other tumors for which this virus has been implicated in pathogenesis, such as EBV‐positive Hodgkin disease (HD), has not been demonstrated clearly. METHODS To investigate the antitumor effects and toxicity of allogeneic EBV CTL in EBV‐positive HD, the authors initiated a pilot trial in which EBV CTL were cultured from allogeneic, partially human leukocyte antigen‐matched donors and were infused into patients who had therapy‐refractory disease. The first cohort of 3 patients (Cohort I) received 3 separate infusions of EBV CTL (5.0 × 106 EBV CTL/kg per dose), and the second cohort (Cohort II) received 30 mg/m2 per day of fludarabine for 3 days followed by a single CTL infusion (1.5 × 107 EBV CTL/kg). RESULTS All three patients in Cohort I had decreases in measurable disease after EBV CTL infusions, and one of those patients was without evidence of disease 22 months after infusion. Two of 3 patients in Cohort II had decreases in measurable disease, although it was not determined whether those decreases were related to fludarabine or to CTL, and 1 patient in Cohort II had 7 months without disease progression. Unlike the patients in Cohort I, fludarabine recipients did not have increases in antidonor CTL responses. Donor cells could not be detected in any of the CTL recipients. CONCLUSIONS Adoptive immunotherapy with allogeneic EBV CTL was safe for patients with recurrent, refractory, EBV‐positive HD; and clinical responses may be observed without the establishment of detectable donor lymphoid chimerism. Cancer 2004. © 2004 American Cancer Society. Adoptive immunotherapy with allogeneic, Epstein–Barr virus (EBV)‐specific cytotoxic T‐lymphocytes (CTL) for patients with recurrent, refractory, EBV‐positive Hodgkin disease was safe and resulted in disease regression without the establishment of donor CTL chimerism. Although recipients of immunosuppressive chemotherapy did not have detectable CTL against donor cells, the patients did not have donor CTL chimerism postinfusion or improved clinical outcome.