title: CsA exposure is associated with acute GVHD and relapse in children after SCT.
abstract: CsA is commonly used after haematological SCT (HSCT) as GVHD prophylaxis. In solid organ transplantation, area under the blood concentration vs time curve (AUC) correlates with clinical outcome. However, in HSCT, it has not been determined whether the AUC is superior to trough level monitoring to optimize clinical efficacy of CsA therapy. Therefore, the aim of this study was to investigate the relationships between CsA trough levels and/or AUC early after HSCT with clinical outcome. A total of 91 children (1.1-17.3 years) were treated consecutively with HSCT for a haematological malignancy. CsA trough levels were obtained and were used to estimate the AUC, retrospectively, with a NONMEM (Non-Linear Mixed Effects Modelling) method. Subsequently, these exposure parameters were correlated to the occurrence of acute GVHD, relapse risk (RR) and OS. Low CsA trough levels were found to correlate with the occurrence of acute GVHD. In addition, a CsA AUC over 3000 mcg h/l in AML patients was associated with a higher RR and a reduced OS. This was not the case for ALL patients. Thus, monitoring CsA exposure early after HSCT and adjusting the CsA dose to a predefined target trough level and AUC may provide a tool to influence GVHD/GVL balance.
authors.affiliation: Department of Paediatrics, Division of Immunology, Haematology, Oncology and Bone Marrow Transplantation and Autoimmune Diseases, Leiden University Medical Centre, Leiden, The Netherlands. A.J.Willemze@lumc.nl
authors.forename: A J
authors.initials: AJ
authors.lastname: Willemze
authors.forename: R R
authors.initials: RR
authors.lastname: Press
authors.forename: A C
authors.initials: AC
authors.lastname: Lankester
authors.forename: R M
authors.initials: RM
authors.lastname: Egeler
authors.forename: J
authors.initials: J
authors.lastname: den Hartigh
authors.forename: J M
authors.initials: JM
authors.lastname: Vossen
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D019540:Area Under Curve; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000493:pharmacokinetics*; D016903:Drug Monitoring; D005260:Female; D006086:Graft vs Host Disease / Q000139:chemically induced*; D019337:Hematologic Neoplasms / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics; D007223:Infant; D008297:Male; D012008:Recurrence; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine