Infusion of donor lymphocytes expressing the herpes simplex virus thymidine kinase suicide gene for recurrent hematologic malignancies after allogeneic hematopoietic stem cell transplantation

• Published in: International journal of hematology 2015-07, Vol.102 (1), p.101-110
• Main Authors: Hashimoto, Hisayoshi, Kitano, Shigehisa, Ueda, Ryosuke, Ito, Ayumu, Tada, Kohei, Fuji, Shigeo, Yamashita, Takuya, Tomura, Daisuke, Nukaya, Ikuei, Mineno, Junichi, Fukuda, Takahiro, Mori, Shinichiro, Takaue, Yoichi, Heike, Yuji
• Format: Article
• Language: English
• Subjects: Adult; Biomarkers; Cell Survival - drug effects; Cell- and Tissue-Based Therapy; Cytotoxicity, Immunologic; Female; Ganciclovir - therapeutic use; Graft Survival; Graft vs Host Disease - etiology; Graft vs Host Disease - therapy; Hematologic Neoplasms - diagnosis; Hematologic Neoplasms - therapy; Hematology; Hematopoietic Stem Cell Transplantation - adverse effects; Herpes simplex virus; Humans; Immunophenotyping; Lymphocyte Activation; Lymphocytes - drug effects; Lymphocytes - metabolism; Male; Medicine; Medicine & Public Health; Middle Aged; Oncology; Original Article; Recurrence; Simplexvirus - genetics; Thymidine Kinase - genetics; Transplantation, Homologous; Treatment Outcome
• ISSN: 0925-5710; 1865-3774
• DOI: 10.1007/s12185-015-1801-5

The infusion of donor lymphocytes expressing the herpes simplex virus thymidine kinase suicide gene (TK-cells) is a promising strategy for the treatment of hematologic malignancies relapsing after allogeneic hematopoietic stem cell transplantation. Here we report the results of a phase I clinical trial designed to examine the feasibility, safety, and efficacy of donor lymphocyte infusion (DLI) of TK-cells. Three patients (two with malignant lymphomas, one with acute myeloid leukemia) were enrolled in the trial and received a single DLI of 1 × 10 7 or 5 × 10 7 TK-cells/kg. No local or systemic toxicity related to the gene-transfer procedure was observed. Two patients achieved stable disease. No patient had severe graft-versus-host disease requiring systemic steroid and/or ganciclovir administration. TK-cells were detected in the peripheral blood of all three patients by PCR, but did not persist longer than 28 days. Analysis of cytotoxic T lymphocyte activity detected no immune response against TK-cells by the recipient’s own T cells. Flow cytometric analysis showed low proliferative activity and cytotoxic function of TK-cells. In conclusion, DLI of TK-cells was safely performed in all three patients. Our analysis suggests the probable cause of rapid disappearance of TK-cells to be insufficient in vivo expansion of TK-cells in these patients.