title: Higher therapeutic CsA levels early post transplantation reduce risk of acute GVHD and improves survival.
abstract: We studied whether early CsA trough levels were associated with the risk of acute GVHD in 337 patients after either sibling PBSC or double umbilical cord blood transplantation. All patients, regardless of donor type, started CsA at a dose of 5 mg/kg i.v. divided twice daily, targeting trough concentrations 200-400 ng/mL. The CsA level was studied by a weighted average method calculated by giving 70% of the weight to the level that was measured just before the onset of the event or day +30. We found that higher weighted average CsA trough levels early post transplantation contributed to lower risk of acute GVHD, and lower non-relapse and overall mortality. Thus, our data support close monitoring with active adjustments of CsA dosing to maintain therapeutic CsA levels in the first weeks of allo-HCT. In patients who are near or even modestly above the CsA target trough level, in the absence of CsA-related toxicity, dose reduction should be cautious to avoid subtherapeutic drug levels resulting in higher risk of acute GVHD.
authors.affiliation: University of Minnesota Blood and Marrow Transplant Program, Minneapolis, MN, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Rogosheske
authors.affiliation: University of Minnesota Blood and Marrow Transplant Program, Minneapolis, MN, USA.
authors.forename: A D
authors.initials: AD
authors.lastname: Fargen
authors.affiliation: University of Minnesota Blood and Marrow Transplant Program, Minneapolis, MN, USA.
authors.forename: T E
authors.initials: TE
authors.lastname: DeFor
authors.affiliation: University of Minnesota Blood and Marrow Transplant Program, Minneapolis, MN, USA.
authors.forename: E
authors.initials: E
authors.lastname: Warlick
authors.affiliation: University of Minnesota Blood and Marrow Transplant Program, Minneapolis, MN, USA.
authors.forename: M
authors.initials: M
authors.lastname: Arora
authors.affiliation: University of Minnesota Blood and Marrow Transplant Program, Minneapolis, MN, USA.
authors.forename: B R
authors.initials: BR
authors.lastname: Blazar
authors.affiliation: University of Minnesota Blood and Marrow Transplant Program, Minneapolis, MN, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Weisdorf
authors.affiliation: University of Minnesota Blood and Marrow Transplant Program, Minneapolis, MN, USA.
authors.forename: C G
authors.initials: CG
authors.lastname: Brunstein
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D065095:Calcineurin Inhibitors; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods*; D016572:Cyclosporine / Q000008:administration & dosage*; D005260:Female; D006086:Graft vs Host Disease; D019337:Hematologic Neoplasms / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012008:Recurrence; D012189:Retrospective Studies; D012307:Risk Factors; D035781:Siblings; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine
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