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

• Type of Material: Article
• Authors: Jeannine S. McCune, University of Washington; Christine M. Quinones, Beckman Research Institute; James Ritchie, Emory University; Paul A. Carpenter, University of Washington; Erik van Maarsveen, University Medical Center Utrecht; Rosa F. Yeh, Seattle Cancer Care Alliance; Claudio Anasetti, H. Lee Moffitt Cancer Center and Research Institute; Jaap J. Boelens, University Medical Center Utrecht; Nelson Hamerschlak, Hospital Israelita Albert Einstein; Moustapha Hassan, Karolinska University Hospital Stockholm; Hyoung Jin Kang, Seoul National Univeristy; Yoshinobu Kanda, Jichi Medical University; Angelo Paci, Paris Sud University; Miguel-Angel Perales, Memorial Sloan Kettering Cancer Center; Peter J. Shaw, Children's Hospital at Westmead; Victoria L. Seewaldt, Beckman Research Institute; Bipin N. Savani, Vanderbilt University; Angela Hsieh, McKesson Specialty Health; Betsy Poon, AdventHealth for Children; Mohamed Mohty, Hôpital Saint-Antoine; Michael A. Pulsipher, Children's Hospital Los Angeles; Marcelo Paquini, Medical College of Wisconsin; L. Lee Dupuis, University of Toronto
• Language: English
• Date: 2019-09-30
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: 2019 Elsevier
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.bbmt.2019.05.021
• Title of Journal or Parent Work: BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
• Volume: 25
• Issue: 9
• Start Page: 1890
• End Page: 1897
• Grant/Funding Information: This work was supported by National Institutes of Health, National Cancer Institute (NCI) grant CA182963, P30 CA033572 (Multiscale Translational Research Core) and Dr. McCune’s startup funds provided by City of Hope.
• Keywords: Busulfan; Hematopoietic Cell Transplantation; Delphi process; pharmacokinetic; precision medicine
• Research Categories: Biology, Molecular; Health Sciences, Medicine and Surgery; Biology, Cell

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.