Abstract
Busulfan, a bifunctional alkylating agent, remains a cornerstone in hematologic oncology and transplantation medicine despite the advent of targeted therapies. Originally developed for chronic myeloid leukemia, its current primary application lies in myeloablative conditioning for hematopoietic stem cell transplantation (HSCT). Busulfan exerts its cytotoxic effects through DNA cross-linking, inducing apoptosis in rapidly dividing cells. Its pharmacokinetics are influenced by genetic polymorphisms in glutathione S-transferase enzymes, necessitating therapeutic drug monitoring to balance efficacy and toxicity. Clinical advances, including intravenous formulations and pharmacokinetic-guided dosing, have improved safety outcomes. Ongoing research explores liposomal formulations, gene therapy conditioning, and integration into precision medicine frameworks. While toxicity—particularly hepatic veno-occlusive disease and pulmonary fibrosis—remains a concern, innovations in personalized dosing and pharmacogenomics continue to enhance its therapeutic index. This review highlights Busulfan’s evolving clinical roles, challenges, and future prospects in oncology and regenerative medicine.
Keywords: Busulfan; Alkylating Agent; Hematopoietic Stem Cell Transplantation; Pharmacokinetics; Therapeutic Drug Monitoring; Myeloablation; Pharmacogenomics; Veno-Occlusive Disease; Gene Therapy; Precision Medicine
References
- Hassan M, Ehrsson H and Ljungman P. “Busulfan pharmacokinetics and therapeutic drug monitoring: Clinical implications in hematopoietic stem cell transplantation”. Clinical Pharmacokinetics 59.6 (2020): 747-763.
- Bartelink IH., et al. “Busulfan dose adjustment for intravenous and oral administration: A review of pharmacokinetic-guided strategies”. Biology of Blood and Marrow Transplantation 22.8 (2016): 1443-1452.
- Chattergoon DS, Saunders EF and Klein J. “Pharmacogenetics of busulfan: The role of glutathione S-transferase polymorphisms”. Therapeutic Drug Monitoring 41.5 (2019): 592-601.
- Ciurea SO and Andersson BS. “Busulfan in hematopoietic stem cell transplantation: Pharmacology, dosing, and future perspectives”. Expert Opinion on Drug Metabolism & Toxicology 15.8 (2019): 671-685.
- Vassal G., et al. “High-dose busulfan in conditioning regimens: Balancing efficacy and toxicity through therapeutic drug monitoring”. Bone Marrow Transplantation 41.6 (2008): 459-465.
- Zwaveling J., et al. “Population pharmacokinetics of intravenous busulfan in children and adults undergoing stem cell transplantation”. Clinical Pharmacology & Therapeutics 103.4 (2018): 652-661.
- Dvorak CC., et al. “Busulfan dosing in pediatric hematopoietic stem cell transplantation: Advances in pharmacokinetic modeling”. Frontiers in Pharmacology 12 (2021): 630921.
- Andersson BS., et al. “Intravenous busulfan: Optimizing myeloablation while minimizing toxicity in transplant conditioning regimens”. Biology of Blood and Marrow Transplantation 23.4 (2017): 558-566.
- Nguyen L., et al. “Precision dosing of busulfan in hematopoietic stem cell transplantation: The role of pharmacogenomics and modeling”. Frontiers in Pharmacology 13 (2022): 828732.
- De Lima M., et al. “Reduced-intensity conditioning with fludarabine and busulfan: Clinical outcomes and future prospects”. Leukemia 32.2 (2018): 392-400.