title: Clinical and pharmacological risk factors for acute graft-versus-host disease after paediatric bone marrow transplantation from matched-sibling or unrelated donors.
abstract: The aim of this study was to identify the risk factors for acute graft-versus-host disease (aGVHD) in children transplanted from a matched-sibling donor (MSD) or an unrelated donor (UD). In all, 87 children consecutively underwent allogeneic bone marrow transplantation (BMT) from MSD (n=36), and UD (n=51). GVHD prophylaxis included CsA alone (n=33) or with MTX (n=51). ATG was added in UD-BMT and thalassemic recipients. CsA whole-blood concentrations were measured by EMIT and the dosing regimen was monitored by Bayesian pharmacokinetic modelling. Trough blood concentration (TBC) during the first 2 weeks post transplantation was lower in children who developed grade II-IV aGVHD than those developing no GVHD or only grade I (57+/-9 vs 94+/-8 ng/ml, P=0.007), whereas peak blood concentration and area under concentration curve vs time were similar in both groups. TBC <85 ng/ml and 'use of MTX' were associated with aGVHD in MSD-SCT (P=0.003 and 0.007, respectively) as well as in UD-SCT (P=0.006 and 0.003). Donor age >or=8 years was significant only in MSD-BMT. Our results have shown the significant decisive role of pharmacological factors such as CSA TBC or use of MTX in the occurrence of GVHD in MSD as well as in UD paediatric BMT.
authors.affiliation: Department of Pharmacy, Debrousse Hospital, Lyon, France.
authors.forename: P
authors.initials: P
authors.lastname: Martin
authors.forename: N
authors.initials: N
authors.lastname: Bleyzac
authors.forename: G
authors.initials: G
authors.lastname: Souillet
authors.forename: C
authors.initials: C
authors.lastname: Galambrun
authors.forename: Y
authors.initials: Y
authors.lastname: Bertrand
authors.forename: P H
authors.initials: PH
authors.lastname: Maire
authors.forename: R W
authors.initials: RW
authors.lastname: Jelliffe
authors.forename: G
authors.initials: G
authors.lastname: Aulagner
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D019540:Area Under Curve; D001499:Bayes Theorem; D016026:Bone Marrow Transplantation / Q000009:adverse effects* / Q000276:immunology / Q000379:methods; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000517:prevention & control*; D006648:Histocompatibility; D006801:Humans; D015994:Incidence; D007223:Infant; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D012307:Risk Factors; D014019:Tissue Donors
chemical_list: D016572:Cyclosporine; D008727:Methotrexate