title: Higher plasma bilirubin predicts veno-occlusive disease in early childhood undergoing hematopoietic stem cell transplantation with cyclosporine.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Kwi Suk Kim, Hyang Sook Kim, Sang Geon Kim, Department of Pharmacy, Seoul National University Hospital, Seoul 03080, South Korea.
authors.forename: Kwi Suk
authors.initials: KS
authors.lastname: Kim
authors.affiliation: Kwi Suk Kim, Hyang Sook Kim, Sang Geon Kim, Department of Pharmacy, Seoul National University Hospital, Seoul 03080, South Korea.
authors.forename: Aree
authors.initials: A
authors.lastname: Moon
authors.affiliation: Kwi Suk Kim, Hyang Sook Kim, Sang Geon Kim, Department of Pharmacy, Seoul National University Hospital, Seoul 03080, South Korea.
authors.forename: Hyoung Jin
authors.initials: HJ
authors.lastname: Kang
authors.affiliation: Kwi Suk Kim, Hyang Sook Kim, Sang Geon Kim, Department of Pharmacy, Seoul National University Hospital, Seoul 03080, South Korea.
authors.forename: Hee Young
authors.initials: HY
authors.lastname: Shin
authors.affiliation: Kwi Suk Kim, Hyang Sook Kim, Sang Geon Kim, Department of Pharmacy, Seoul National University Hospital, Seoul 03080, South Korea.
authors.forename: Young Hee
authors.initials: YH
authors.lastname: Choi
authors.affiliation: Kwi Suk Kim, Hyang Sook Kim, Sang Geon Kim, Department of Pharmacy, Seoul National University Hospital, Seoul 03080, South Korea.
authors.forename: Hyang Sook
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Kwi Suk Kim, Hyang Sook Kim, Sang Geon Kim, Department of Pharmacy, Seoul National University Hospital, Seoul 03080, South Korea.
authors.forename: Sang Geon
authors.initials: SG
authors.lastname: Kim
keywords: Adverse drug reaction; Cyclosporine; Hematopoietic stem cell transplantation; Total bilirubin; Veno-occlusive disease