Retrospective Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Transplant. Jun 24, 2016; 6(2): 403-410
Published online Jun 24, 2016. doi: 10.5500/wjt.v6.i2.403
Higher plasma bilirubin predicts veno-occlusive disease in early childhood undergoing hematopoietic stem cell transplantation with cyclosporine
Kwi Suk Kim, Aree Moon, Hyoung Jin Kang, Hee Young Shin, Young Hee Choi, Hyang Sook Kim, Sang Geon Kim
Kwi Suk Kim, Hyang Sook Kim, Sang Geon Kim, Department of Pharmacy, Seoul National University Hospital, Seoul 03080, South Korea
Aree Moon, College of Pharmacy, Duksung Women’s University, Seoul 01369, South Korea
Hyoung Jin Kang, Hee Young Shin, Department of Pediatrics, Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, South Korea
Young Hee Choi, College of Pharmacy, Dongguk University, Goyang, Gyeonggi-do 410-820, South Korea
Sang Geon Kim, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 03080, South Korea
Author contributions: Kim KS, Moon A and Kim SG for conception and design of the study; Kim KS, Choi YH and Kim SG for analysis and interpretation; Kim KS and Kim HS for data collection; Kim KS, Choi YH and Kim SG for writing the article; Kang HJ for critical revision of the article; Kim KS, Shin HY and Kim SG for final approval of the article; Kim KS and Choi YH for statistical analysis; Kim KS and Kim SG for overall responsibility.
Supported by The Education and Research Encouragement Fund of Seoul National University Hospital.
Institutional review board statement: This study was approved by the Institutional Review Board of Seoul National University Hospital (SNUH; H-1112-087-390, 2012.3.17), a 1961-bed medical center, on March 17, 2012.
Informed consent statement: The authors petition BPG for waiver of informed consent because this study was not a clinical trial, but was retrospectively done using anonymized electronic medical records of the study subjects. In addition, authors declared that the study subjects were at no risk due to this study.
Conflict-of-interest statement: We have no financial relationships to disclose.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Sang Geon Kim, PhD, Professor, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, 101 Daehak-ro Jongno-gu, Seoul 03080, South Korea. sgk@snu.ac.kr
Telephone: +82-2-8807840 Fax: +82-2-8807840
Received: January 2, 2016
Peer-review started: January 3, 2016
First decision: February 2, 2016
Revised: February 22, 2016
Accepted: March 17, 2016
Article in press: March 18, 2016
Published online: June 24, 2016
Processing time: 171 Days and 20.7 Hours
Abstract

AIM: To analyze the association between plasma bilirubin levels and veno-occlusive disease (VOD) in non-adult patients undergoing hematopoietic stem cell transplantation (HSCT) during cyclosporine therapy.

METHODS: A total of 123 patients taking cyclosporine were evaluated using an electronic medical system at the Seoul National University Children’s Hospital from the years 2004 through 2011. Patients were grouped by age and analyzed for incidence and type of adverse drug reactions (ADRs) including VOD.

RESULTS: The HSCT patients were divided into three age groups: G#1 ≥ 18; 9 ≤ G#2 ≤ 17; and G#3 ≤ 8 years of age). The majority of transplant donor types were cord blood transplantations. Most prevalent ADRs represented acute graft-vs-host disease (aGVHD) and VOD. Although the incidences of aGVHD did not vary among the groups, the higher frequency ratios of VOD in G#3 suggested that an age of 8 or younger is a risk factor for developing VOD in HSCT patients. After cyclosporine therapy, the trough plasma concentrations of cyclosporine were lower in G#3 than in G#1, indicative of its increased clearance. Moreover, in G#3 only, a maximal total bilirubin level (BILmax) of ≥ 1.4 mg/dL correlated with VOD incidence after cyclosporine therapy.

CONCLUSION: HSCT patients 8 years of age or younger are more at risk for developing VOD, diagnosed as hyperbilirubinemia, tender hepatomegaly, and ascites/weight gain after cyclosporine therapy, which may be represented by a criterion of plasma BILmax being ≥ 1.4 mg/dL, suggestive of more sensitive VOD indication in this age group.

Keywords: Hematopoietic stem cell transplantation; Veno-occlusive disease; Cyclosporine; Adverse drug reaction; Total bilirubin

Core tip: This study analyzed the association between plasma bilirubin and veno-occlusive disease (VOD) in childhood undergoing hematopoietic stem cell transplantation (HSCT) during cyclosporine therapy. Here, we report that age of 8 or under may be a risk factor for VOD in CsA-treated patients who underwent HSCT with differential clearance of CsA. Another finding is that a criterion of 1.4 mg/dL of plasma maximal total bilirubin level or higher content alone closely represents the incidence of VOD in early childhood patients with HSCT in CsA therapy. Information shown in this study would be of great help to understand VOD occurring during CsA medication and to find optimal pharmacotherapy in HSCT patients.