Sirolimus exposure and the occurrence of cytomegalovirus DNAemia after allogeneic hematopoietic stem cell transplantation
Por:
Piñana JL, Perez-Pitarch A, Guglieri-Lopez B, Giménez E, Hernandez-Boluda JC, Terol MJ, Ferriols-Lisart R, Solano C and Navarro D
Publicada:
1 dic 2018
Resumen:
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.
Filiaciones:
Piñana JL:
Department of Hematology, Fundación de investigación, INCLIVA, Hospital Clínico Universitario, Valencia, Spain
Department of Hematology, Hospital Universitari i Politècnic La Fe, València, Spain
CIBERONC, Instituto Carlos III, Madrid, Spain
Perez-Pitarch A:
Pharmacy Department, Hospital Clínico Universitario, Valencia, Spain
:
Pharmacy Department, Hospital Universitario Doctor Peset, Valencia, Spain
Giménez E:
Microbiology Service, Hospital Clínico Universitario, Valencia, Spain
Hernandez-Boluda JC:
Department of Hematology, Fundación de investigación, INCLIVA, Hospital Clínico Universitario, Valencia, Spain
Terol MJ:
Department of Hematology, Fundación de investigación, INCLIVA, Hospital Clínico Universitario, Valencia, Spain
Ferriols-Lisart R:
Pharmacy Department, Hospital Clínico Universitario, Valencia, Spain
Solano C:
Department of Hematology, Fundación de investigación, INCLIVA, Hospital Clínico Universitario, Valencia, Spain
Department of Medicine, School of Medicine, University of Valencia, Valencia, Spain
Navarro D:
Microbiology Service, Hospital Clínico Universitario, Valencia, Spain
Department of Microbiology, School of Medicine, University of Valencia, Valencia, Spain
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