Hematology/oncology units performing conditioning prior to stem cell transplantation
Key Highlights
Busulfan is metabolized mainly in the liver via glutathione conjugation producing metabolites including sulfolane implicated in neurotoxicity.
Approximately 10% of patients receiving high-dose busulfan experience seizures, necessitating anticonvulsant prophylaxis.
Sulfolane and related metabolites cross the blood-brain barrier and induce convulsions and hypothermia in animal models.
Guideline-Based Recommendations
Diagnosis
Monitor patients receiving high-dose busulfan for neurological symptoms including seizures.
Therapeutic drug monitoring of busulfan plasma levels to guide dosing and reduce toxicity risk.
Management
Use anticonvulsant prophylaxis such as phenytoin or diazepam during busulfan conditioning regimens.
Adjust busulfan dosing based on therapeutic drug monitoring to minimize neurotoxicity.
Monitoring & Follow-up
Regular neurological assessment during and after busulfan administration.
Monitor body temperature for hypothermia as a sign of CNS toxicity.
Risks
High-dose busulfan can cause CNS toxicity manifesting as seizures and hypothermia.
Neurotoxic metabolites such as sulfolane contribute to these adverse effects.
Patient & Prescribing Data
Patients undergoing conditioning prior to hematopoietic stem cell transplantation
Busulfan administered orally at 2 mg/kg twice daily for 4 days with dose adjustments guided by plasma monitoring; anticonvulsant prophylaxis recommended due to seizure risk.
Clinical Best Practices
Implement therapeutic drug monitoring of busulfan plasma concentrations to optimize dosing.
Administer anticonvulsant prophylaxis routinely in patients receiving high-dose busulfan.
Monitor neurological status and body temperature closely during busulfan conditioning.
Consider the role of busulfan metabolites in CNS toxicity when evaluating adverse neurological events.
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