AUTOLOGOUS LYMPHOKINE-ACTIVATED KILLER-CELL THERAPY OF EPSTEIN-BARR-VIRUS-POSITIVE AND EPSTEIN-BARR-VIRUS-NEGATIVE LYMPHOPROLIFERATIVE DISORDERS ARISING IN ORGAN TRANSPLANT RECIPIENTS

Lymphoreticular malignancies, collectively called posttransplant lymph oproliferative disorders (PTLD), eventually develop in 2-5% of organ t ransplant recipients. They frequently undergo regression when immunosu ppression is reduced or stopped. This feature has been associated with a previous or de novo Epstein-Barr virus (EBV) infection, We herein d escribe immunotherapy with autologous lymphokine-activated killer (LAK ) cells in seven patients with PTLD (four EBV-positive patients and th ree EBV-negative patients), Autologous peripheral blood mononuclear ce lls were obtained by leukapheresis, depleted of monocytes, and culture d in the presence of interleukin 2 for 10 to 11 days. A single dose of 5.2 x 10(9) to 5.6 x 10(10) LAK cells was given intravenously. System ic interleukin 2 was not administered. The four patients with EBV+ PTL D had complete tumor regression; two of them developed controllable re jection. Three patients are well 13-16 months after treatment; the fou rth patient died of pneumonia 41 days after infusion. Three patients w ith EBV- lymphomas had no response despite prior evidence that their t umors also were subject to immune surveillance. Two of these three pat ients died after being given other treatment, and the third patient ha s persistent tumor. In conclusion, autologous LAK cell infusion was ef fective for treatment of four EBV+ organ transplant recipients, LAK ce ll efficacy for three patients with EBV- PTLD was not evaluable under the management circumstances in which this treatment was utilized.