TY - JOUR
T1 - Therapeutic drug monitoring of busulfan in patients undergoing hematopoietic cell transplantation
T2 - A pilot single-center study in taiwan
AU - Chen, Rong Long
AU - Fang, Li Hua
AU - Yang, Xin Yi
AU - Amrani, Mohsin El
AU - Uijtendaal, Esther Veronique
AU - Chen, Yen Fu
AU - Ku, Wei Chi
N1 - Funding Information:
Funding: This research was funded by the Taipei Pathology Institute, Taipei, Taiwan, grant number “TIP-106-009”. The APC was funded by Taipei Pathology Institute, Taipei, Taiwan, and Fu Jen Catholic University, New Taipei, Taiwan.
Funding Information:
This research was funded by the Taipei Pathology Institute, Taipei, Taiwan, grant number “TIP-106-009”. The APC was funded by Taipei Pathology Institute, Taipei, Taiwan, and Fu Jen Catholic University, New Taipei, Taiwan. Acknowledgments: We thanked the Mass Spectrometry Laboratory of Tzong Jwo Jang, College of Medicine, Fu Jen Catholic University, New Taipei, Taiwan, for technical assistance with the LC–MS instrumentation. We also thanked Arjen M. Punt and Kim van der Elst in the Department of Clinical Pharmacy, Division Laboratory, Medicine and Pharmacy, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands, for useful discussions.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/6/26
Y1 - 2021/6/26
N2 - Busulfan has been used as a conditioning regimen in allogeneic hematopoietic cell stem transplantation (HSCT). Owing to a large inter-individual variation in pharmacokinetics, therapeutic drug monitoring (TDM)-guided busulfan dosing is necessary to reduce graft failure and relapse rate. As there exists no TDM of busulfan administration for HCT in Taiwan, we conducted a pilot study to assess the TDM-dosing of busulfan in the Taiwanese population; Seven patients with HCT from The Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan, received conditioning regimens consisting of intravenous busulfan and other chemotherapies. After the initial busulfan dose, blood samples were collected for busulfan TDM at 5 min, 1 h, 2 h, and 3 h. Busulfan was extracted and detected by performing stable-isotope dilution LC–MS/MS. Plasma busulfan concentration was quantified and used for dose adjustment. Potential adverse effects of busulfan, such as mucositis and hepatic veno-occlusive disease (VOD), were also evaluated; The LC–MS/MS method was validated with an analyte recovery of 88–99%, within-run and between-run precision of <15%, and linearity ranging from 10 to 10,000 ng/mL. Using TDM-guided busulfan dosing, dose adjustment was necessary and performed in six out of seven patients (86%) with successful engraftments in all patients (100%). Mild mucositis was observed, and VOD was diagnosed in only one patient; This single-center study in Taiwan demonstrated the importance of busulfan TDM in increasing the success rate of HCT transplantation. It is also necessary to further investigate the optimal busulfan target value in the Taiwanese population in the future.
AB - Busulfan has been used as a conditioning regimen in allogeneic hematopoietic cell stem transplantation (HSCT). Owing to a large inter-individual variation in pharmacokinetics, therapeutic drug monitoring (TDM)-guided busulfan dosing is necessary to reduce graft failure and relapse rate. As there exists no TDM of busulfan administration for HCT in Taiwan, we conducted a pilot study to assess the TDM-dosing of busulfan in the Taiwanese population; Seven patients with HCT from The Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan, received conditioning regimens consisting of intravenous busulfan and other chemotherapies. After the initial busulfan dose, blood samples were collected for busulfan TDM at 5 min, 1 h, 2 h, and 3 h. Busulfan was extracted and detected by performing stable-isotope dilution LC–MS/MS. Plasma busulfan concentration was quantified and used for dose adjustment. Potential adverse effects of busulfan, such as mucositis and hepatic veno-occlusive disease (VOD), were also evaluated; The LC–MS/MS method was validated with an analyte recovery of 88–99%, within-run and between-run precision of <15%, and linearity ranging from 10 to 10,000 ng/mL. Using TDM-guided busulfan dosing, dose adjustment was necessary and performed in six out of seven patients (86%) with successful engraftments in all patients (100%). Mild mucositis was observed, and VOD was diagnosed in only one patient; This single-center study in Taiwan demonstrated the importance of busulfan TDM in increasing the success rate of HCT transplantation. It is also necessary to further investigate the optimal busulfan target value in the Taiwanese population in the future.
KW - Busulfan
KW - Hematopoietic cell transplantation
KW - Therapeutic drug monitoring
UR - http://www.scopus.com/inward/record.url?scp=85109378358&partnerID=8YFLogxK
U2 - 10.3390/ph14070613
DO - 10.3390/ph14070613
M3 - Article
C2 - 34206798
AN - SCOPUS:85109378358
SN - 1424-8247
VL - 14
SP - 1
EP - 10
JO - Pharmaceuticals
JF - Pharmaceuticals
IS - 7
M1 - 613
ER -