Myleran (Busulfan)

Busulfan is an alkylating antineoplastic agent used in specific hematologic malignancies and transplant conditioning.

• Chronic myeloid leukemia (CML): reduces leukemic cell proliferation and helps achieve disease control.
• Acute myeloid leukemia (AML) conditioning: incorporated into high‑dose regimens to eradicate residual disease before stem cell transplantation.
• Hematopoietic stem cell transplantation (HSCT) conditioning: provides myeloablation to facilitate donor cell engraftment.

• Busulfan exerts its cytotoxic effect by alkylating nucleophilic sites on DNA, forming intra‑ and interstrand cross‑links that impede DNA replication and transcription. The resulting DNA damage triggers apoptosis in rapidly dividing cells, particularly malignant hematopoietic progenitors, thereby producing its antineoplastic activity. The drug is metabolized primarily by glutathione S‑transferase in the liver, producing inactive metabolites that are eliminated renally. Its pharmacokinetic profile is characterized by a narrow therapeutic window, requiring careful monitoring of plasma concentrations during high‑dose therapy.

Busulfan may cause a range of adverse reactions, varying from mild to severe, and patients should be monitored closely.

Common Side Effects

• Nausea and vomiting: gastrointestinal upset that may require anti‑emetic therapy.
• Oral mucositis: painful inflammation of the mouth lining, affecting eating and speaking.
• Alopecia (hair loss): temporary loss of scalp and body hair during treatment.

Serious or Rare Side Effects

• Pulmonary fibrosis or interstitial lung disease: progressive scarring of lung tissue that can impair breathing.
• Hepatic veno‑occlusive disease (SOS): blockage of small hepatic veins leading to liver enlargement and jaundice.
• Severe bone marrow suppression leading to pancytopenia: marked reduction of red cells, white cells and platelets, increasing infection and bleeding risk.

Before initiating Busulfan therapy, several precautionary measures should be observed to minimize risks.

• Blood count monitoring: perform regular complete blood counts to detect myelosuppression early.
• Liver function assessment: evaluate hepatic enzymes and bilirubin prior to treatment and during therapy.
• Pregnancy avoidance: avoid use in pregnant women unless benefits outweigh risks; advise effective contraception.
• Seizure prophylaxis: consider anticonvulsant prophylaxis for patients at risk of high plasma concentrations.
• Dose adjustment in hepatic impairment: reduce dose or extend interval in patients with significant liver dysfunction.
• Store at ambient temperature: keep tablets in the original container, protect from moisture and light.

Busulfan can interact with other medicines, affecting its toxicity or efficacy.

Major Interactions (Avoid)

• Cyclophosphamide: combined use increases risk of severe myelosuppression and organ toxicity.
• Azathioprine: concurrent administration may amplify bone marrow suppression.
• High‑dose radiation therapy: may exacerbate pulmonary toxicity when given together.

Moderate Interactions (Monitor Closely)

• Acetaminophen: concurrent use can add hepatic stress, requiring liver function monitoring.
• Antifungal azoles (e.g., fluconazole): may alter Busulfan metabolism and plasma levels.
• Phenytoin: can reduce Busulfan concentrations, potentially decreasing therapeutic effect.