ADOPTIVE IMMUNOTHERAPY FOR LEUKEMIA - DONOR LYMPHOCYTES TRANSDUCED WITH THE HERPES-SIMPLEX THYMIDINE KINASE GENE FOR REMISSION INDUCTION

This study will evaluate the safety and efficacy of allogenic donor ly mphocyte infusions in patients who have relapsed hematologic malignanc ies after allogeneic bone marrow transplantation (BMT). Donor lymphocy te transfusions have resulted in the cure of some patients with relaps ed leukemia or lymphoproliferative disorder after allogeneic BMT, but has been complicated by the development of graft versus host disease ( GvHD). We hypothesize that a retroviral vector containing the Herpes s implex thymidine kinase (HStk) gene will allow for retention of the an ti-leukemia response of transfused donor lymphocytes while allowing fo r the adverse effects of GVHD to be mitigated. Patients with relapsed hematologic malignancies after allogeneic BMT will be infused with ex vivo gene modified donor lymphocytes. The Herpes Simplex thymidine kin ase (HStk) gene will be transduced into the cells ex vivo using LTKOSN . I vector supernate. Insertion of the HStk gene into lymphocytes conf ers a sensitivity to the anti-herpes drug ganciclovir (GCV). This sele ctive destruction of donor lymphocytes in situ will be used to abrogat e the effect of graft versus host disease, if it develops.