Significance of therapeutic dose monitoring of busulfan and targeted dose adjustment in transplantation

Abstract

 Busulfan is widely used as an important component of conditioning regimens for hematopoietic cell transplantation. Large individual differences are well recognized, and both overdosing and underdosing blood concentration can adversely affect transplant outcomes. To overcome this individual heterogeneity, dosage adjustments are made based on therapeutic dose monitoring are conducted. This personalization is especially necessary when performing transplants for diseases in which blood concentrations have been shown to be directly related to transplant outcomes, or when performing transplants in children. Recent clinical trials using busulfan are increasingly described with targeted range of busulfan rather than fixed doses per body weight. When a standard of care is established based on the results of these clinical trials, dose adjustment by therapeutic dose monitoring will be necessary to reproduce those results in real-world clinical practice. For safer and more effective transplantation, it is desirable to establish a system to widely measure blood levels of busulfan.