- Class: Alkylating agent – bifunctional DNA cross-linker (alkyl sulfonate).
- Type: Oral or intravenous cytotoxic chemotherapy.
Mechanism of Action (MOA)
- Alkylates DNA at N7 position of guanine → forms inter- and intra-strand DNA cross-links.
- Inhibits DNA replication and transcription → induces apoptosis.
- Cell cycle non-specific, affects rapidly dividing cells.
Clinical Uses
- Hematopoietic stem cell transplantation (HSCT) – conditioning regimen for allogeneic or autologous transplant.
- Chronic myeloid leukemia (CML) – less common today, usually pre-transplant or in older regimens.
- Part of combination chemotherapy for other myeloid malignancies in selected protocols.
Dosing (Adults)
- Oral: 0.8 mg/kg every 6 hours for 4 days (total 16 doses) – historically used in HSCT conditioning.
- IV: 0.8 mg/kg every 6 hours or 3.2 mg/kg/day continuous infusion for 4 days.
- Dose adjustments:
- Hepatic impairment
- Pharmacokinetic monitoring for therapeutic window to reduce toxicity.
Toxicities
- Hematologic: profound myelosuppression – dose-limiting.
- Pulmonary toxicity: idiopathic interstitial pneumonitis / “busulfan lung” – can be fatal.
- Hepatic: veno-occlusive disease (VOD) / sinusoidal obstruction syndrome.
- Seizures – especially at high IV doses (prophylactic antiepileptics like phenytoin or levetiracetam often given).
- Nausea, vomiting, mucositis.
- Alopecia.
Monitoring
- CBC with differential – frequent during therapy.
- Liver function tests; monitor for VOD.
- Pulmonary function and symptoms – cough, dyspnea.
- Therapeutic drug monitoring (TDM) for IV busulfan to optimize exposure (AUC-guided dosing).
- Seizure prophylaxis for high-dose regimens.
Summary
Busulfan (Myleran®, Busulfex®) is an alkylating agent used primarily in HSCT conditioning. Key concerns are myelosuppression, pulmonary toxicity, VOD, and seizures, requiring CBC, liver function, pulmonary monitoring, and seizure prophylaxis, with therapeutic drug monitoring for IV dosing.