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Sirolimus exposure and the occurrence of cytomegalovirus DNA emia after allogeneic hematopoietic stem cell transplantation
Author(s) -
Piñana José Luis,
PerezPitarch Alejandro,
GuglieriLopez Beatriz,
Giménez Estela,
HernandezBoluda Juan Carlos,
Terol María José,
FerriolsLisart Rafael,
Solano Carlos,
Navarro David
Publication year - 2018
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.14754
Subject(s) - sirolimus , medicine , hematopoietic stem cell transplantation , cytomegalovirus , transplantation , serostatus , tacrolimus , human cytomegalovirus , immunology , gastroenterology , viral load , herpesviridae , viral disease , virus
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 DNA emia: 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 DNA emia. Increasing the tacrolimus trough concentration from 0 to 16 ng/ mL increased the probability of patients having detectable CMV DNA emia 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 DNA emia, but levels >8 ng/ mL significantly decreased the number of detectable CMV DNA emia 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 DNA emia events become detectable as sirolimus exposure increases.