Implementation and evaluation of busulfan pharmacokinetics in adult hematopoietic stem cell transplantation

Purpose This study aimed to describe the implementation of busulfan pharmacokinetic (PK)-based dosing adjustments, assess the safety and efficacy of a test-dose strategy for monitoring busulfan PK, and standardize PK assessment in adult hematopoietic stem cell transplantation (HSCT). Methods Adult patients who underwent myeloablative HSCT with PK-monitored busulfan from July 2023 to April 2024 were analyzed to assess efficacy and toxicity, including mucositis, veno-occlusive disease (VOD), engraftment, relapse, and death. The first and second therapeutic busulfan doses were determined using a test dose of 0.8 mg/kg. The area under the plasma concentration-time curve (AUC) was calculated, with a target AUC (AUC target ) range of 4800–5300 µM*minute. The third and fourth therapeutic busulfan doses were further adjusted based on the AUC of the first dose (AUC first ). AUC weight was calculated to predict the AUC using a weight-based strategy of 3.2 mg/kg myeloablative busulfan dose. The primary outcome was the percentage of patients achieving AUC target within 10%, 15%, and 20% for both AUC weight and AUC first . Results Since July 2023, a total of 13 patients have successfully undergone busulfan PK monitoring for myeloablative conditioning, achieving a 100% engraftment rate. PK-guided first dosing improved achieving the target AUC within ±10% in 63% of patients. All patients developed grade 2 or higher mucositis, with no other notable toxicities, such as VOD, reported to date. Conclusion PK-guided dosing improves target AUC achievement for adult patients undergoing myeloablative HSCT, highlighting the importance of PK monitoring for individualized patient care.