Monitoring of Trough Plasma Ganciclovir Levels and Peripheral Blood Cytomegalovirus (CMV)-Specific CD8 ⁺ T Cells To Predict CMV DNAemia Clearance in Preemptively Treated Allogeneic Stem Cell Transplant Recipients

Abstract

It is uncertain whether monitoring plasma ganciclovir (GCV) levels is useful in predicting cytomegalovirus (CMV) DNAemia clearance in preemptively treated allogeneic stem cell transplant recipients. In this observational study, including 13 episodes of CMV DNAemia treated with intravenous (i.v.) GCV or oral valganciclovir, we showed that monitoring trough plasma GCV levels does not reliably predict response to therapy. Rather, immunological monitoring (pp65 and immediate-early [IE]-1-specific gamma interferon [IFN-␥]-producing CD8؉ T cells) appeared to perform better for this purpose.

Systematic review of ganciclovir pharmacodynamics during the prevention of cytomegalovirus infection in adult solid organ transplant recipients

“…At present, GCV and ValGCV dosing decisions are not routinely informed by use of a therapeutic range. The target cut‐offs for C min vary across different laboratories and range between 0.06 and 2.5 μg/mL in human organ and tissue transplant studies . The dose‐dependent inhibition of human CMV replication by GCV has been established in vitro, with a reported 50% inhibitory concentration of 1.5 μg/mL …”

“…25 Despite these reports, contrasting results were found in pharmacodynamic studies investigating the relationship between the therapeutic effect of different GCV blood concentrations. 23,[25][26][27][28] Consequently, there is currently no consensus regarding the use of clinical drug monitoring for GCV in SOT recipients, although given the low but significant numbers of transplant recipients failing therapy, the use of antiviral concentration monitoring needs to be considered.…”

New advances in the management of cytomegalovirus in allogeneic haemopoietic stem cell transplantation

“…TDM facilitates optimal dosing of antivirals as therapeutic levels may vary depending upon renal function, particularly in the case of ganciclovir . Dose adjustment based on population pharmacokinetics Bayesian prediction model has been demonstrated to optimise exposure in solid organ transplantation, although a study of TDM in HSCT showed that immune status is more important than trough ganciclovir levels in predicting clearance of CMV during pre‐emptive therapy . TDM is not routinely available at present but can be performed in a research setting.…”

“…20 Dose adjustment based on population pharmacokinetics Bayesian prediction model has been demonstrated to optimise exposure in solid organ transplantation, 20 although a study of TDM in HSCT showed that immune status is more important than trough ganciclovir levels in predicting clearance of CMV during pre-emptive therapy. 21 TDM is not routinely available at present but can be performed in a research setting. Further research is warranted in HSCT recipients to optimise ganciclovir and valganciclovir dosage, and for use with novel antivirals where less is known about doseresponse relationships.…”

Expanding role of cytomegalovirus as a human pathogen

“…It has been increasingly recognized that sequential immunological monitoring of CMV-specific T-cell immunity during episodes of active CMV infection may help to individually tailor the dosing and duration of antiviral therapy. This will perhaps result in shorter courses and thus less drug-related toxicity and a lower incidence of recurrent episodes of CMV replication [Sester et al, 2001;Gerna et al, 2006Gerna et al, , 2011Nebbia et al, 2008;Abate et al, 2010;Benmarzouk-Hidalgo et al, 2011;Solano et al, 2011;Lisboa et al, 2012;Gim enez et al, 2014b].…”