Adverse Events Associated with Busulfan in HSCT Pre-Transplant Conditioning: A Retrospective Pharmacovigilance Study of the FAERS Database

Background: Busulfan had been approved as a pre-transplant conditioning agent for allogeneic hematopoietic stem cell transplantation (HSCT) in chronic myeloid leukemia. However, the real-world data on its safety in a large sample population is imprecise. We assessed the adverse signals associated with busulfan specifically used as a pre-transplant conditioning agent for HSCT through data mining of the FDA pharmacovigilance database. Method: This article extracted adverse events (AEs) from the FAERS database from the first quarter of 2004 to the third quarter of 2024, and determined the signal strength of AEs using Reporting Odds Ratio, Proportional Reporting Ratio, Bayesian Confidence Propagation Neural Network, and Empirical Bayesian Geometric Mean. Result: The study identified 3627 AE reports associated with busulfan limited indication for pre-transplant conditioning for HSCT, with 11489 Preferred Terms-annotated entries. The most frequently reported AEs were primarily categorized under Infections And Infestations, Injury, Poisoning And Procedural Complications. Notably, some AEs, such as Pulmonary Hypertension, Thrombotic Microangiopathy is not mentioned in the drug labeling. In the disproportionality analysis, Blood Follicle Stimulating Hormone Increased and Blood Luteinising Hormone Increased had high ROR value. We screened the concomitant medication reports with HSCT pre-conditioning as the indication and found that, in the reports of busulfan in combination with fludarabine, the AEs of Acute Graft Versus Host Disease, Infection showed positive results in the disproportionality analysis, which is different from the combination with cyclophosphamide. Conclusion: In recent years, busulfan has been mainly used for HSCT conditioning treatment rather than the initial treatment of chronic myeloid leukemia. In this study, we screened the AE reports of busulfan applied to HSCT pre-transplantation treatment in the FAERS database to demonstrate more precisely the AEs occurring in the current clinical application of busulfan. Further disproportionality analysis provides useful information for the clinical application of busulfan, which is expected to promote its safe use in clinical practice.