Abstract
I. Scientific Abstract
This study will evaluate the safety and efficacy of allogenic donor lymphocyte infusions in patients who have relapsed hematologic malignancies after allogeneic bone marrow transplantation (BMT). Donor lymphocyte transfusions have resulted in the cure of some patients with relapsed 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 simplex thymidine kinase (HStk) gene will allow for retention of the anti-leukemia response of transfused donor lymphocytes while allowing for 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 kinase (HStk) gene will be transduced into the cells ex vivo using LTKOSN. 1 vector supernate. Insertion of the HStk gene into lymphocytes confers a sensitivity to the anti-herpes drug ganciclovir (GCV). This selective destruction of donor lymphocytes in situ will be used to abrogate the effect of graft versus host disease, if it develops.
II. Nontechnical Abstract
After going through bone marrow transplant to treat their leukemia, some patients develop recurrent disease. These patients can occasionally be brought back into remission by administering white blood cells from the same person that originally donated the bone marrow for their transplant. Unfortunately, these donor white blood cells can have side effects and react against the patient's normal tissues. This process, called graft versus host disease, can kill the patient. This study attempts to use a gene transfer method to alter the donated cells, in order to be able to kill them later if they react against the patient's body.
We have investigated the possibility of placing genes into white blood cells so that they become sensitive to a type of chemotherapy that is not harmful to normal parts of the body. The gene we have selected is called the Herpes Simplex thymidine kinase (HStk) gene, one of many genes contained within the Herpes Simplex Virus. The Herpes simplex virus can be killed by a drug called ganciclovir (GCV). By transferring the HStk gene into the white blood cells, using a disabled mouse virus called a vector, we can convert the cell to be genetically like a herpes virus. The HStk-containing white blood cell can now be killed with GCV. If a patient develops a bad reaction from the donated, gene-altered white blood cells, we can administer GCV to hopefully kill these cells and stop graft versus host disease.
Get full access to this article
View all access options for this article.