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Nucleic Acids as Therapeutic Targets and Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
When administered orally, busulfan causes significantly less nausea and vomiting than other DNA cross-linking agents and is therefore more acceptable to patients. Thus, when used to treat CML, it can keep patients almost symptom-free for long periods of time with relatively few side effects. However, frequent blood tests are necessary because myelosuppression may result in irreversible bone-marrow aplasia. Skin hyperpigmentation is also a common side effect during oral therapy, and progressive interstitial pulmonary fibrosis may occur more rarely. Other less frequent side effects include seizures, hepatic toxicity (i.e., veno-occlusive disease), and wasting syndrome. Levetiracetam has proved effective as prophylaxis for busulfan-induced seizures, and the anticonvulsant phenytoin is sometimes administered concurrently to prevent seizures, and benzodiazepines can be used to ameliorate busulfan-induced seizures when they are in progress. Finally, busulfan is a Group 1 carcinogen, and so should be avoided during conception, pregnancy and breast feeding.
Respiratory, endocrine, cardiac, and renal topics
Published in Evelyne Jacqz-Aigrain, Imti Choonara, Paediatric Clinical Pharmacology, 2021
Evelyne Jacqz-Aigrain, Imti Choonara
Busulfan is administered orally. An intravenous form exists for adults and will be available in the near future for children. Bioavailability is 80% with significant inter-individual variation. Busulfan distributes into the liver, the brain (up to 20% of the dose), the lungs and the bone marrow. The CSF to plasma concentration ratio is 1. The plasma half-life is 3 hours. The clearance is mainly metabolic, less than 1% is eliminated unchanged in the urine, and is higher in children than in adults. Busulfan, like other alkylating agents, is conjugated to glutathione by the glutathione-transferases [2].
Hematopoietic Stem Cell Transplantation for Multiple Sclerosis
Published in Richard K. Burt, Alberto M. Marmont, Stem Cell Therapy for Autoimmune Disease, 2019
Athanasios Fassas, Richard K. Burt
Two conditioning regimens were employed: (a) Twenty-five patients received BEAM (BCNU 300 mg/m2—etoposide 800 mg/m2-cytaribine 800 mg/m2—melphalan 140 mg/m2). (b) Ten patients were treated with busulfan at 16 mg/kg over 4 days. The patients were rescued with peripheral blood stem cells, mobilized with cyclophosphamide (CY) at 4 g/m2 and G- or GM-CSF at 5 or 10 μg/kg/day. No steroids were given during mobilization. In 10 cases, a degree of ex vivo T cell-depletion was performed by CD34+ cell-selection of the grafts. All 35 patients also received rabbit antithymocyte globulin (ATG, Merieux/Sangstat) at total doses ranging from 5 mg/kg to 20 mg/kg, mainly soon after the infusion of stem cells (in vivo T depletion).
Antioxidant and anti-inflammatory protective effects of rutin and kolaviron against busulfan-induced testicular injuries in rats
Published in Systems Biology in Reproductive Medicine, 2022
Sunny O. Abarikwu, Rex-Clovis C. Njoku, Ifeoma G. John, Benjamin A. Amadi, Chidimma J. Mgbudom-Okah, Chigozie L. Onuah
Accordingly, the goal of relieving the deleterious impact of busulfan on male fertility health is gaining much traction in the public space and in different laboratories worldwide (Li et al. 2018; Nasimi et al. 2018; Ezirim et al. 2019; Abarikwu et al. 2020). Interestingly, phytochemicals are at the epicenter of these therapeutic intervention paradigms due to their plethora of biological activities and tissue-protective potentials (Olayinka et al. 2014; Nafees et al. 2015; Abarikwu et al. 2017). A treatment regimen that involves combining different phytochemicals or their extracts from seeds, nuts or fruits can enhance or reduce the bioavailability and pharmacological effects conferred by the individual phytochemical (Phan et al. 2018a). It appears that the combined actions of phytochemicals may elicit heightened or diminished biological properties than the effect of the individual compound (Phan et al. 2018). Therefore, there is the need to evaluate the efficacy of combined phytochemical-based therapies, especially those used as complementary adjuvants, so that their therapeutic potentials are maximized during the treatment of diseases. Synergistic, additive, potentiation, and antagonistic effects are the summative outcomes of these phytochemical mixture interactions that may influence distinct biochemical pathways necessary for cell or tissue survival (Liu 2004; Phan et al. 2018; Negrette-Guzmán 2019).
Acute toxicity and outcome among pediatric allogeneic hematopoietic transplant patients conditioned with treosulfan-based regimens
Published in Pediatric Hematology and Oncology, 2020
Pasi Huttunen, Mervi Taskinen, Kim Vettenranta
Busulfan is a direct alkylating agent and widely used in conditioning for both malignancies and nonmalignant diseases.9,27 It concentrates in the liver, lungs, brain and kidneys, and the well-known complications include SOS/VOD, hemorrhagic cystitis, interstitial pneumonia, permanent alopecia as well as convulsions and mucocitis.10,28 The use of busulfan requires in many cases prophylactic anti-convulsant treatment and guidance by serum concentrations. Busulfan is widely used in combination with cyclophosphamide among children, particularly the youngest, among whom TBI is too toxic. Treosulfan has a more profound immunosuppressive effect than busulfan, and, in some studies, has been more effective against malignant cells in children.29 Furthermore, treosulfan has a more favorable toxicity profile with a limited extramedullary toxicity, e.g. SOS/VOD has been absent or very rare even among adults.7,22 In certain cases dose-targeted busulfan can be considered as an option with a similarly favorable acute toxicity profile,27 but its late toxicity remains to be defined.
Emerging therapies in β-thalassemia: toward a new era in management
Published in Expert Opinion on Emerging Drugs, 2020
Rayan Bou-Fakhredin, Rami Tabbikha, Hisham Daadaa, Ali T. Taher
Then came the TNS9 trial (ClinicalTrials.gov number NCT01639690), which is a phase 1 study treating TDT patients with autologous CD34+ hematopoietic progenitor cells transduced with TNS9, a lentiviral vector encoding the normal human ß-globin gene [51]. Three patients had β0/β+-thalassemia and one patient had β0/β0 thalassemia. Three patients received an 8 mg/kg dose of busulfan, and the fourth patient received a dose of 14 mg/kg of busulfan. The patients received 8.3 to 12.0 CD34+ TNS9.3.55 cells/kg [51]. The transduction in the final CD34+ cell product had a vector copy number (VCN) of 0.25. No toxicity profile greater than grade 3 was observed. All patients showed durable and stable gene marking. There was no evidence of clonal dominance. One patient experienced a significant decrease in transfusion requirements that lasted for more than 5 years.