Harmonization of Busulfan Plasma Exposure Unit (BPEU): A Community-Initiated Consensus Statement

Abstract Busulfan therapeutic drug monitoring (TDM) is often used to achieve target plasma exposures. Variability in busulfan plasma exposure units (BPEU) is a potential source for misinterpretation of publications and protocols and is a barrier to data capture by hematopoietic cell transplantation (HCT) registry databases. We sought to harmonize to one BPEU for international use. Using Delphi consensus methodology, iterative surveys were sent to an increasing number of relevant clinical stakeholders. In Survey 1, 14 respondents were asked to identify ideal properties of a BPEU. In Survey 2, 53 stakeholders were asked: 1) to evaluate BPEU candidates according to: a) ideal BPEU properties established by Survey 1, b) local position statements for TDM and 2) to identify potential facilitators and barriers to adoption of the harmonized BPEU. The most frequently used BPEUs identified in descending order were: area under the curve (AUC) in μM×min, mg×h/L, concentration at steady state (Css) in ng/mL, AUC in μM×h, and μg×h/L. All respondents conceptually agreed on the ideal properties of a BPEU and to adopt a harmonized BPEU. Respondents were equally divided between selecting AUC in μM×min versus mg×h/L for harmonization. AUC in mg×h/L was finally selected as the BPEU, because it satisfied most of the survey-determined ideal properties for the harmonized BPEU and is easily understood in a clinical practice environment. Further, seven major professional societies have endorsed AUC in mg×h/L as the harmonized unit for reporting to HCT registry databases and for use in future protocols and publications.