1995
DOI: 10.1182/blood.v85.11.3048.bloodjournal85113048
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Retrovirally marked CD34-enriched peripheral blood and bone marrow cells contribute to long-term engraftment after autologous transplantation

Abstract: 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 c… Show more

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Cited by 455 publications
(98 citation statements)
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“…Secondly, the concept of stochastic clonal loss has implications for gene therapy using haemopoietic stem cells. If, as is currently the case, only a proportion of transplanted stem cells are successfully transduced (Brenner et al, 1993;Dunbar et al, 1995), in time, although in some individuals expression of the required gene will increase, in most it will decline as the transduced stem cells are lost through differentiation unless some selection/survival pressure can be applied.…”
Section: Discussionmentioning
confidence: 99%
“…Secondly, the concept of stochastic clonal loss has implications for gene therapy using haemopoietic stem cells. If, as is currently the case, only a proportion of transplanted stem cells are successfully transduced (Brenner et al, 1993;Dunbar et al, 1995), in time, although in some individuals expression of the required gene will increase, in most it will decline as the transduced stem cells are lost through differentiation unless some selection/survival pressure can be applied.…”
Section: Discussionmentioning
confidence: 99%
“…myeloma. breast cancer, lymphoma and chronic lymphocytic lymphoma but, so far, no neo-marked relapses have been reported [8][9][10][11]. As the transduction efficiency has been low in most of these studies, the negative fmdings do not exclude that unmarked cells in the harvests have contributed to the disease reoccurrence in these trials as well.…”
Section: Gene-marking Trialsmentioning
confidence: 99%
“…In a study at the National Institutes of Health (NIH) in the USA. patients with myeloma or breast cancer subjected to autologous stem-cell transplantation were reinfused with both bone marrow and peripheral stem cells marked with separate vectors after high-dose chemotherapy [8]. The object of the study was to compare the short-and long-term reconstitution capability of bone-marrow stem cells and peripheral stem cells that had been harvested after mobilization with chemotherapy and granulocyte-colony stimulating factor (G-CSF).…”
Section: Gene-marking Trialsmentioning
confidence: 99%
“…Both mobilized peripheral blood and bone marrow stem cells (PBSC, BMSC) can be used as the source of these cells. We and others have reported the use of both PBSC and BMSC as targets for gene transfer in human clinical protocols whose goal is to autotransplant gene-modi®ed cells (Dunbar, 1996;Dunbar et al, 1995;Hanania et al, 1996;Hesdorffer et al, 1998;Ward et al, 1994Ward et al, , 1996. We have used this autotransplantation system with the human multiple drug resistance (MDR) gene with the goal of up-regulating expression of the MDR protein product, p-glycoprotein, which is required for the ef®cient ef¯ux of natural compounds including many chemotherapeutic agents from cells to avoid their toxic effects.…”
mentioning
confidence: 99%