title: Relationship between CsA trough blood concentration and severity of acute graft-versus-host disease after paediatric stem cell transplantation from matched-sibling or unrelated donors.
abstract: In order to determine optimal CsA trough blood concentrations (TBC) in the early post transplantation period, we analysed relationships between TBC and acute graft-versus-host disease (aGVHD) in paediatric SCT. A total of 94 children consecutively underwent allogeneic stem cell transplantation (SCT) from: matched-sibling (MSD) (n=36), mismatched-related (MMRD) (n=3) and unrelated donors (UD) (n=55). GVHD prophylaxis usually included CsA alone or with methotrexate. Antithymocyte globulin was added in UD-SCT. TBC during the first weeks of post transplantation were estimated retrospectively by a Bayesian pharmacokinetic method and statistically associated with aGVHD. In MSD-SCT, the mean TBC during the first 2 weeks post transplantation were 42+/-10 and 90+/-7 ng/ml, respectively, in patients with grade II-IV and 0-I aGVHD (P=0.001). In SCT from UD and MMRD, TBC were 73+/-4 vs 95+/-8 ng/ml (P=0.284). For TBC >85 ng/ml, no patient developed grade II-IV aGVHD, 10 developed mild aGVHD and 30 had no aGVHD. For TBC <65 ng/ml, 7/11 patients receiving an MSD-SCT and 4/18 receiving an UD- or MMRD-SCT developed grade II-IV aGVHD. The mean TBC corresponding to each grade were: no GVHD: 101+/-10 ng/ml, mild: 77+/-11 ng/ml, moderate: 61+/-13 ng/ml, severe: 56+/-15 ng/ml (P <0.001). These results reveal a strong relationship between TBC during the early post transplantation period and the severity of aGVHD in paediatric SCT.
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; D001499:Bayes Theorem; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000009:adverse effects / Q000097:blood*; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000453:epidemiology / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000097:blood*; D015994:Incidence; D007223:Infant; D008297:Male; D012720:Severity of Illness Index; D035781:Siblings; D014019:Tissue Donors; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine