Cytomegalovirus and Epstein-Barr Virus DNA Kinetics in Whole Blood and Plasma of Allogeneic Hematopoietic Stem Cell Transplantation Recipients

Abstract

Currently, no consensus has been reached on the optimal blood compartment to be used for surveillance of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) DNAemia. Although several comparative studies have been performed correlating CMV and EBV DNA loads in whole blood (WB) versus plasma, to our knowledge, no studies to date have analyzed the kinetics of both viruses in the 2 blood compartments. In this retrospective noninterventional multicenter cohort study, the kinetics of CMV and EBV DNA in 121 hematopoietic stem cell transplantation (HSCT) recipients were investigated by analyzing in parallel 569 and 351 paired samples from 80 and 58 sequential episodes of CMV and EBV DNAemia, respectively. Unlike previous studies, this study used a single automated molecular method that was CE-marked and Food and Drug Administrationapproved for use in quantifying CMV and EBV DNA in both plasma and WB. Furthermore, the complete viral replication kinetics of all episodes (including both the ascending and the descending phases of the active infection) was examined in each patient. The previously observed overall correlation between CMV DNA levels in WB and plasma was confirmed (Spearman's ρ = .85; P < .001). However, although WB and plasma CMV DNAemia reached peak levels simultaneously, in the ascending phase, the median CMV DNA levels in plasma were approximately 1 log10 lower than WB. Furthermore, in patients who received preemptive therapy, CMV DNA showed a delayed decrease in plasma compared with WB. A lower correlation between EBV DNA levels in plasma versus WB was found (Spearman's ρ = .61; P < .001). EBV DNA kinetics was not consistent in the 2 blood compartments, mostly due to the lower positivity in plasma. Indeed, in 19% of episodes, EBV DNA was negative at the time of the EBV DNA peak in WB. Our results suggest a preferential use of WB for surveillance of CMV and EBV infection in HSCT recipients.

Assessment and prevention of cytomegalovirus infection in allogeneic hematopoietic stem cell transplant and in solid organ transplant: A multidisciplinary consensus conference by the Italian GITMO, SITO, and AMCLI societies

“…While a correlation between CMV DNA levels in the two biologic matrices has been demonstrated, plasma DNAemia is about 1 log 10 lower than whole blood DNAemia. In addition, a recent retrospective, multicenter study in allo‐HSCT recipients reported different CMV DNA kinetics in whole blood vs plasma, and a prolonged persistence of CMV DNA following ganciclovir treatment was observed in plasma . The same data have been observed in a kidney transplant population (unpublished data).…”

Advances inCMVinfection prevention and treatment after allo‐HSCT

“…In any case, since CMV DNAemia significantly differs in the two matrices the same biological specimen should be used for a sequential reliable monitoring. In addition, a recent retrospective non‐interventional multicenter cohort study in Italy reported different CMV DNA kinetics in whole blood vs plasma, showing a prolonged persistence of CMV DNA in the latter following ganciclovir treatment . This study seems to suggest that whole blood might be preferred to monitor DNAemia and guide antiviral treatment, considering that DNAemia monitoring using plasma may unnecessarily expose patients to prolonged period of antiviral therapy with possible increase in toxicity.…”

Brief molecular diagnostic criteria for human cytomegalovirus infection/disease

“…In fact, the pre-treatment of plasma samples with DNase showed that most HCMV DNA detected in plasma was naked DNA and not virion DNA. Thus, monitoring of HCMV DNA in whole blood of HSCT recipients was shown to better reflect the viral replication kinetics, enabling PET to be discontinued earlier and more safely [23]. Detection of HCMV IE or late transcripts by NASBA as an alternative marker of virus replication was investigated in two clinical trials [24,25].…”