USE OF DONOR T-LYMPHOCYTES EXPRESSING HERPES-SIMPLEX THYMIDINE KINASEIN ALLOGENEIC BONE-MARROW TRANSPLANTATION - A PHASE I-II STUDY

Allogeneic bone marrow transplantation (BMT) is associated with a seve re complication; graft-versus-host disease (GvHD). While effectively p reventing GvHD, ex-vivo T lymphocyte marrow depletion unfortunately in creases graft rejection and reduces the graft-versus-leukemia (GvL) ef fect. The ex-vivo transfer of the herpes simplex thymidine kinase (HS- tk) suicide gene into T cells before their infusion with hematopoietic stem cells should allow for selective in vivo depletion of these T ce lls with ganciclovir (GCV) if subsequent GvHD was to occur. Thus, one could preserve the beneficial effects of the T cells on engraftment an d tumor control in patients not experiencing severe GvHD. We have demo nstrated that retroviral-mediated transfer of HS-tk and Neomycin resis tance genes in T-lymphocytes followed by G418 selection results in T-c ells specifically inhibited by GCV with no bystander effect. Escalatin g amounts of HS-tk expressing T-cells will be infused in conjunction w ith a T-cell depleted marrow grafts to allogeneic HLA identical leukem ic recipients. Toxicity, survival, alloreactivity and GCV-sensitivity of the gene-modified cells will be monitored. Patients with leukemia u ndergoing an HLA-matched allogeneic BMT associated with a high risk of GvHD will be enrolled in the protocol.