Busulfan in hematopoietic stem cell transplant setting

Area of Science:

• Pharmacology
• Hematology
• Oncology

Background:

• Busulfan is a key agent in hematopoietic stem cell transplantation (HCT) due to its marrow toxicity.
• Both oral and intravenous (i.v.) formulations of busulfan are available.
• Sinusoidal obstruction syndrome is a primary toxicity associated with busulfan therapy.

Purpose of the Study:

• To review recent data on busulfan pharmacokinetics and pharmacodynamics in HCT.
• To evaluate the role of therapeutic drug monitoring (TDM) in HCT patients.
• To assess novel strategies for personalizing busulfan dosing.

Main Methods:

• Systematic review of literature published in the last decade.
• Analysis of pharmacokinetic and pharmacodynamic data.
• Evaluation of clinical outcomes and toxicity in HCT patients.

Main Results:

• Variability in systemic busulfan concentrations persists despite i.v. formulation and weight-based dosing.
• A correlation exists between busulfan plasma exposure and clinical outcomes in HCT.
• Current evidence suggests glutathione S-transferase (GST) polymorphisms do not accurately predict busulfan clearance for personalized dosing.

Conclusions:

• Therapeutic drug monitoring remains crucial for optimizing busulfan therapy in HCT.
• Personalized dosing strategies are under investigation to improve efficacy and reduce toxicity.
• Glutathione S-transferase (GST) polymorphisms are not currently suitable for individualizing busulfan dosage.