ArticleExperimental hematology2006
Busulfan pharmacokinetics, toxicity, and low-dose conditioning for autologous transplantation of genetically modified hematopoietic stem cells in the rhesus macaque model.
Article in Experimental hematology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02629120 (High Dose Peripheral Blood Stem Cell Transplantation With Post Transplant Cyclophosphamide for Patients With Chronic Granulomatous Disease), which is not on this map. Cited by 22 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
High Dose Peripheral Blood Stem Cell Transplantation With Post Transplant Cyclophosphamide for Patients With Chronic Granulomatous Disease
Who cites it
22 citing papers in PubMed, 36 citations in OpenAlex.
- Trial
- Intra-ovarian busulfan administration: an effective and relatively safe method for depleting endogenous germ cells in the female marine teleost yellow drum (Nibea albiflora).Fish physiology and biochemistry · 2026Article
- Comparison of total body irradiation (TBI) and Non-TBI conditioning regimens for allogeneic hematopoietic stem cell transplantation in patients with peripheral T cell lymphoma: a multicenter retrospective study in China.Annals of hematology · 2025Article
- Efficient manufacturing and engraftment ofMolecular therapy. Methods & clinical development · 2023Article
- Pre-existing anti-factor VIII immunity alters therapeutic platelet-targeted factor VIII engraftment following busulfan conditioning through cytotoxic CD8 T cells.Journal of thrombosis and haemostasis : JTH · 2023Article
- Models and Methods for Evaluating Regeneration of Spermatogenesis After Cytotoxic Treatments.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Immunoresponse to Gene-Modified Hematopoietic Stem Cells.Molecular therapy. Methods & clinical development · 2020Review
- Busulfan Combined with Immunosuppression Allows Efficient Engraftment of Gene-Modified Cells in a Rhesus Macaque Model.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Article
- A swine model of acute thrombocytopenia with prolonged bleeding time produced by busulfan.Experimental animals · 2016Article
- Total body irradiation must be delivered at high dose for efficient engraftment and tolerance in a rhesus stem cell gene therapy model.Molecular therapy. Methods & clinical development · 2016Article
- From bench to bedside: preclinical evaluation of a self-inactivating gammaretroviral vector for the gene therapy of X-linked chronic granulomatous disease.Human gene therapy. Clinical development · 2013Article
- Hematopoietic stem cell gene therapy:assessing the relevance of preclinical models.Seminars in hematology · 2013Review
- Spermatogonial stem cell transplantation into rhesus testes regenerates spermatogenesis producing functional sperm.Cell stem cell · 2012Article
- Stem cell factor-displaying simian immunodeficiency viral vectors together with a low conditioning regimen allow for long-term engraftment of gene-marked autologous hematopoietic stem cells in macaques.Human gene therapy · 2012Article
- Gene therapy of chronic granulomatous disease: the engraftment dilemma.Molecular therapy : the journal of the American Society of Gene Therapy · 2011Review
- Efficient and stable MGMT-mediated selection of long-term repopulating stem cells in nonhuman primates.The Journal of clinical investigation · 2010Article
- Transgene expression levels determine the immunogenicity of transduced hematopoietic grafts in partially myeloablated mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2009Article
- Busulfan produces efficient human cell engraftment in NOD/LtSz-Scid IL2Rgamma(null) mice.Stem cells (Dayton, Ohio) · 2009Article
- Erythroid-specific human factor IX delivery from in vivo selected hematopoietic stem cells following nonmyeloablative conditioning in hemophilia B mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2008Article
- Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 1 country.
Funding
Abstract
objectiveGene 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.
methodsBusulfan 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.
resultsBusulfan 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%.
conclusionsWe 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.