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- W1980785906 abstract "Gene transfer to hematopoietic stem cells has recently been demonstrated to benefit a small number of patients in whom a selective advantage is conferred upon genetically modified cells; however, in disorders where no such selective advantage is conferred, conditioning appears necessary to allow adequate engraftment. To decrease the toxicity profile, we sought to develop nonmyeloablative conditioning regimens and in this work, explored the use of intravenous busulfan in a large animal model.Busulfan pharmacokinetics and toxicity were monitored in young rhesus macaques at two dosing levels (4 and 6 mg/kg). These doses were then employed to condition two animals at each dose level prior to autologous transplantation of genetically modified cells using our standard methods.Busulfan pharmacokinetic (PK) data showed the area under the curve (AUC), drug half-life, and drug clearance were consistent within each dose group and similar to those reported in children. Single doses of busulfan were well tolerated and produced dose-dependent myelosuppression, most notably in the neutrophil and platelet counts. Although marking levels reached over 1% early in one animal, the long-term marking was low but detectable at 0.01 to 0.001%.We conclude that low-dose intravenous bolus infusion of busulfan is well tolerated, has dose-dependent effects on peripheral blood counts, and allows long-term engraftment of genetically modified cells, but at levels too low for most clinical disorders." @default.
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- W1980785906 date "2006-02-01" @default.
- W1980785906 modified "2023-09-26" @default.
- W1980785906 title "Busulfan pharmacokinetics, toxicity, and low-dose conditioning for autologous transplantation of genetically modified hematopoietic stem cells in the rhesus macaque model" @default.
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- W1980785906 doi "https://doi.org/10.1016/j.exphem.2005.10.010" @default.
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