title: Impact of cyclosporine-A concentration on the incidence of severe acute graft-versus-host disease after allogeneic stem cell transplantation.
abstract: This single-center retrospective study analyzed 85 consecutive patients who underwent allogeneic stem cell transplantation (allo-SCT) with the aim to assess whether there is a correlation between exposure to cyclosporine-A (CsA; as measured by CsA concentrations during the first month after allo-SCT) and the risk for developing severe grade III-IV acute graft-versus-host disease (aGVHD). The median concentrations of CsA in the blood at 1, 2, 3, and 4 weeks after allo-SCT were 348 (range: 172-733), 284 (range: 137-535), 274 (range: 107-649), and 247 (range: 37-695) ng/mL, respectively. Overall, grade II-IV aGVHD occurred in 36 patients (42%) at a median of 29 (range: 6-100) days after allo-SCT. The incidence of grade III-IV aGVHD (n = 20) was 23% (95% confidence interval [CI], 14%-32%). In univariate analysis, patients receiving allo-SCT from an HLA-matched unrelated donor had a higher risk of grade III-IV aGVHD, and patients having the lowest CsA concentration in the first and second weeks after allo-SCT had a significantly higher risk of grade III-IV aGVHD. In a multivariate logistic regression analysis, a higher CsA concentration measured during the first week following graft infusion was the strongest parameter significantly associated with a reduced risk of severe grade II-IV aGVHD (P = .012; relative risk [RR] = 0.24; 95% CI, 0.08-0.73). Of note, when adjusted by donor type, CsA concentration in week 1 remained significantly associated with risk of severe grade II-IV aGVHD (P = .014). We conclude that precise monitoring of CsA concentrations and adjustment of CsA dose early after allo-SCT may be effective to prevent onset of severe aGVHD.
authors.affiliation: Centre Hospitalier et Universitaire (CHU) de Nantes, Service d'Hématologie Clinique, Nantes, France.
authors.forename: Florent
authors.initials: F
authors.lastname: Malard
authors.forename: Richard M
authors.initials: RM
authors.lastname: Szydlo
authors.forename: Eolia
authors.initials: E
authors.lastname: Brissot
authors.forename: Patrice
authors.initials: P
authors.lastname: Chevallier
authors.forename: Thierry
authors.initials: T
authors.lastname: Guillaume
authors.forename: Jacques
authors.initials: J
authors.lastname: Delaunay
authors.forename: Sameh
authors.initials: S
authors.lastname: Ayari
authors.forename: Viviane
authors.initials: V
authors.lastname: Dubruille
authors.forename: Steven
authors.initials: S
authors.lastname: Le Gouill
authors.forename: Beatrice
authors.initials: B
authors.lastname: Mahe
authors.forename: Thomas
authors.initials: T
authors.lastname: Gastinne
authors.forename: Nicolas
authors.initials: N
authors.lastname: Blin
authors.forename: Beatrice
authors.initials: B
authors.lastname: Saulquin
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Harousseau
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreau
authors.forename: Mohamad
authors.initials: M
authors.lastname: Mohty
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D016572:Cyclosporine / Q000097:blood* / Q000627:therapeutic use; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology* / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood* / Q000627:therapeutic use; D015994:Incidence; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013223:Statistics as Topic; D033581:Stem Cell Transplantation / Q000009:adverse effects* / Q000401:mortality; D013997:Time Factors; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine