Sirolimus exposure and the occurrence of cytomegalovirus DNAemia after allogeneic hematopoietic stem cell transplantation.
Am J Transplant
; 18(12): 2885-2894, 2018 12.
Article
de En
| MEDLINE
| ID: mdl-29603596
ABSTRACT
Sirolimus appears to protect against cytomegalovirus (CMV) in organ transplant recipients. The effect of this drug in allogeneic hematopoietic stem cell transplantation recipients remains unexplored. By means of multivariate continuous-time Markov model analyses, we identified 3 independent covariates that significantly impacted the risk of CMV DNAemia recipient/donor CMV serostatus, tacrolimus exposure, and sirolimus exposure. CMV-seropositive recipients with CMV-seronegative donors had a significantly higher probability of having detectable CMV DNAemia. Increasing the tacrolimus trough concentration from 0 to 16 ng/mL increased the probability of patients having detectable CMV DNAemia by 40% (from 40% to 80%), whereas this probability decreased by 25% (from 40% to 15%) when trough concentrations of sirolimus increased from 0 to 16 ng/mL. Sensitivity analysis showed that sirolimus exposure between 0 and 6 ng/mL has no or negligible effect on CMV DNAemia, but levels >8 ng/mL significantly decreased the number of detectable CMV DNAemia cases (the risk ratios decreased from 0.68 to 0.21 when whole blood sirolimus concentrations changed from 8 to 18 ng/mL, P < .01). In conclusion, we used a pharmacometric statistical tool to provide the first clinical evidence that fewer CMV DNAemia events become detectable as sirolimus exposure increases.
Mots clés
antibiotic: antiviral; basic (laboratory) research/science; bone marrow/hematopoietic stem cell transplantation; clinical research/practice; immunosuppressant-calcineurin inhibitor: tacrolimus; immunosuppressant-mechanistic target of rapamycin: sirolimus; infection and infectious agents-viral: cytomegalovirus (CMV); infectious disease; pharmacokinetics/pharmacodynamics; pharmacology
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Virémie
/
ADN viral
/
Infections à cytomégalovirus
/
Transplantation de cellules souches hématopoïétiques
/
Sirolimus
/
Cytomegalovirus
Type d'étude:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limites:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Pays/Région comme sujet:
Europa
Langue:
En
Journal:
Am J Transplant
Sujet du journal:
TRANSPLANTE
Année:
2018
Type de document:
Article
Pays d'affiliation:
Espagne