busulfan

Overview

Busulfan is an alkylating antineoplastic agent used primarily in conditioning regimens before hematopoietic stem cell transplantation (HSCT). In this setting, it contributes to myeloablation and immunosuppression, helping eradicate diseased hematopoietic cells and facilitate engraftment of donor stem cells. Its clinical use is especially important in transplantation protocols for hematologic malignancies, including pediatric acute lymphoblastic leukemia (ALL), where exposure control is considered critical to balancing efficacy and toxicity.

Pharmacologically, busulfan has a narrow therapeutic window, and interpatient variability in exposure is a major concern. Because both underexposure and overexposure can affect transplant outcomes, busulfan is commonly monitored using therapeutic drug monitoring and pharmacokinetic analysis. Recent research has therefore focused on refining busulfan dosing, measuring plasma levels accurately, and defining exposure targets in allogeneic HSCT.

Focus of Latest Publications

Recent publications have continued to position busulfan as a central component of myeloablative conditioning for allogeneic hematopoietic stem cell transplantation. One study on cost-efficient internal standard strategies for busulfan quantification emphasized that busulfan plays a central role in conditioning regimens for HSCT, and investigated analytical approaches to improve therapeutic drug monitoring. This work focused on busulfan plasma levels and the use of busulfan-d8 as an internal standard in liquid chromatogram tandem mass spectrometry, with attention to adduct formation that could affect measurement reliability.

Another recent study examined whether refining busulfan exposure improves outcomes in pediatric patients with acute lymphoblastic leukemia undergoing allogeneic HSCT. The publication highlighted that the optimal busulfan exposure window in this population remains to be defined, underscoring the ongoing need for pediatric population pharmacokinetic model development and exposure-guided dosing. The study context indicates that busulfan exposure is being evaluated as a determinant of transplant success in children with ALL, where precise pharmacokinetic control may be especially important.

A third publication described prophylaxis of graft-versus-host disease after allogeneic HSCT in patients who all received myeloablative busulfan-based conditioning and HLA-matched related or unrelated peripheral blood stem cell grafts. In that setting, busulfan served as the conditioning backbone alongside other therapies used in transplant protocols, including methotrexate, tacrolimus, tocilizumab, and total body irradiation in related clinical contexts. The busulfan-based regimen provided the common transplant platform on which graft-versus-host disease prophylaxis strategies were evaluated.

Across these studies, busulfan is consistently treated not as a disease target but as a key therapeutic agent whose exposure, formulation, and integration into conditioning regimens may influence transplant outcomes. The recent literature emphasizes both analytical precision in measuring busulfan and clinical precision in optimizing its use in HSCT, particularly in pediatric ALL and myeloablative transplant settings.

Key Publications

• Jun A cost-efficient internal standard approach for busulfan quantification: MS-based investigation of adduct formation in therapeutic drug monitoring. (Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences, 2026, PMID 42295591): "Busulfan plays a central role in conditioning regimens for hematopoietic stem cell transplantation (HSCT)."
• May Refining busulfan exposure enhances pediatric ALL HSCT outcomes: insights from the International FORUM study. (Blood advances, 2026, PMID 41779961): "The optimal busulfan exposure window in pediatric patients with acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (HSCT) remains to be defined."
• Apr Tildrakizumab for the prophylaxis of graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. (Blood advances, 2026, PMID 41632629): "All patients received myeloablative busulfan-based conditioning and were transplanted with HLA-matched related or unrelated peripheral blood stem cell grafts."