HSV-TK Gene Transfer into Donor Lymphocytes for Control of Allogeneic Graft-Versus-Leukemia

TLDR

In allogeneic bone marrow transplantation, donor lymphocytes are essential for graft‑versus‑leukemia and immune reconstitution, yet their use is constrained by the risk of severe graft‑versus‑host disease. Eight patients who relapsed or developed Epstein‑Barr virus–induced lymphoma after T‑cell–depleted BMT were treated with donor lymphocytes transduced with the HSV‑TK suicide gene. The transduced lymphocytes persisted up to 12 months, produced antitumor activity in five patients, and GvHD in three patients was controllable by ganciclovir‑induced elimination, showing that genetic manipulation can enhance both efficacy and safety of allo‑BMT.

Abstract

In allogeneic bone marrow transplantation (allo-BMT), donor lymphocytes play a central therapeutic role in both graft-versus-leukemia (GvL) and immune reconstitution. However, their use is limited by the risk of severe graft-versus-host disease (GvHD). Eight patients who relapsed or developed Epstein-Barr virus–induced lymphoma after T cell–depleted BMT were then treated with donor lymphocytes transduced with the herpes simplex virus thymidine kinase (HSV-TK) suicide gene. The transduced lymphocytes survived for up to 12 months, resulting in antitumor activity in five patients. Three patients developed GvHD, which could be effectively controlled by ganciclovir-induced elimination of the transduced cells. These data show that genetic manipulation of donor lymphocytes may increase the efficacy and safety of allo-BMT and expand its application to a larger number of patients.