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- Title
1107. Gene Therapy Clinical Trials for Relapsed Leukemia with Infusions of the Suicide-Gene Transduced Donor Lymphocytes in Japan.
- Authors
Onodera, Masafumi; Kaneko, Shin; Otsu, Makoto; Kojima, Hiroshi; Sumazaki, Ryo; Toma, Salvatore; Bonini, Chiara; Bordignon, Claudio; Nakauchi, Hiromitsu; Nagasawa, Toshiro
- Abstract
Donor lymphocytes function as a double-edged sword in allogeneic stem cell transplantation (allo-SCT), that is, they attack leukemic cells (graft versus leukemia-GVL) as well as patient's normal tissues such as liver, intestines, and skin, (graft versus host disease-GVHD). The strong GVL reaction has made an infusion of donor lymphocytes (DLI) an effective treatment for relapsed leukemia after allo-SCT, especially for relapse of chronic myelogenous leukemia. However, the use of DLI is severely limited by the risk of a potential life- threatening complication, GVHD. A phase I/II clinical study of DLI using donor lymphocytes transduced with a retroviral vector carrying the herpes simplex virus thymidine kinase (HSV-TK) gene for patients affected by relapsed leukemia after allo-SCT started at the Tsukuba University Hospital in 2004 as the first clinical trial of leukemia gene therapy in Japan. This is aimed at control of severe GVDH by administration of ganciclovir (GCV) if it occurs while maintaining the maximum GVL effects. So far, we have done eight transduction procedures and infused the HSV-TK transduced donor lymphocytes into 4 patients (2 AML, 1 ALL, and 1 MDS). All patients received about 1×108 cells per kilogram of body weight. In the result, three out of four patients showed good responses such as inhibition of leukemic cell growth and lowering the values of molecular markers after infusions of the transduced cells. One AML patient showed complete remission and no relapse signs are observed on 6 months after the treatment. One patient developed grade III GVHD, and was successfully treated with ganciclovir, in the absence of immunesuppressive drugs. No adverse effects related to gene therapy are observed. Other trials for relapsed leukemia are under way. Details of the present study including additional cases will be presented.Molecular Therapy (2006) 13, S426–S426; doi: 10.1016/j.ymthe.2006.08.1212
- Subjects
LEUKEMIA; GENE therapy; LYMPHOCYTES; GENETIC transduction; HERPES simplex virus
- Publication
Molecular Therapy, 2006, Vol 13, pS426
- ISSN
1525-0016
- Publication type
Article
- DOI
10.1016/j.ymthe.2006.08.1212