Retrovirally marked CD34-enriched peripheral blood and bone marrow cells contribute to long-term engraftment after autologous transplantation
| Autor: | Cynthia Dunbar, Cottler-Fox M, Shaughnessy Ja, O., Doren S, Carter C, Berenson R, Brown S, Rc, Moen, Greenblatt J, Fm, Stewart |
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| Rok vydání: | 1995 |
| Předmět: |
Genetic Markers
Male Filgrastim Antigens CD34 Breast Neoplasms Antigens CD Genes Reporter Granulocyte Colony-Stimulating Factor Humans Cyclophosphamide Melphalan Bone Marrow Transplantation Kanamycin Kinase Graft Survival Hematopoietic Stem Cell Transplantation Genetic Therapy Middle Aged Hematopoietic Stem Cells Recombinant Proteins Phosphotransferases (Alcohol Group Acceptor) Treatment Outcome Female Fluorouracil Multiple Myeloma Whole-Body Irradiation Follow-Up Studies |
| Zdroj: | Europe PubMed Central |
| ISSN: | 0006-4971 |
| Popis: | We report here on a preliminary human autologous transplantation study of retroviral gene transfer to bone marrow (BM) and peripheral blood (PB)-derived CD34-enriched cells. Eleven patients with multiple myeloma or breast cancer had cyclophosphamide and filgrastim-mobilized PB cells CD34-enriched and transduced with a retroviral marking vector containing the neomycin resistance gene, and CD34-enriched BM cells transduced with a second marking vector also containing a neomycin resistance gene. After high-dose conditioning therapy, both transduced cell populations were reinfused and patients were followed over time for the presence of the marker gene and any adverse effects related to the gene-transfer procedure. All 10 evaluable patients had the marker gene detected at the time of engraftment, and 3 of 9 patients had persistence of the marker gene for greater than 18 months posttransplantation. The marker gene was detected in multiple lineages, including granulocytes, T cells, and B cells. The source of the marking was both the transduced PB graft and the BM graft, with a suggestion of better long-term marking originating from the PB graft. The steady-state levels of marking were low, with only 1:1000 to 1:10,000 cells positive. There was no toxicity noted, and patients did not develop detectable replication-competent helper virus at any time posttransplantation. These results suggest that mobilized PB cells may be preferable to BM for gene therapy applications and that progeny of mobilized peripheral blood cells can contribute long-term to engraftment of multiple lineages. |
| Databáze: | OpenAIRE |
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