Early Kinetics of Plasma Cytomegalovirus DNA Load in Allogeneic Stem Cell Transplant Recipients in the Era of Highly Sensitive Real-Time PCR Assays: Does It Have Any Clinical Value?

Abstract

We report that in a population of allogeneic stem cell transplant recipients, determination of the viral doubling time (dt) of the cytomegalovirus (CMV) DNA plasma load predicted the eventual need for inception of preemptive antiviral therapy, whereas the level of the initial plasma CMV DNA load did not. The data thus indicated that determination of the dt of CMV DNA may be useful in the therapeutic management of CMV infection in this clinical setting.

How to Best Manage Cytomegalovirus Infection in the Allogeneic Stem Cell Transplant Setting: Future Prospects

“…We believe that kinetic analyses of plasma CMV DNA load and routine monitoring of CMV-specific T-cell responses may help to achieve these purposes. In effect, we recently showed that a CMV DNA load doubling time (dt) ≤2 days, anticipated the eventual need of preemptive antiviral with a positive predictive value of 100% [13]. We later reported that treating patients upon dt s ≤2 days led to a significant reduction of the time on antiviral therapy [14].…”

Preemptive antiviral therapy for CMV infection in allogeneic stem cell transplant recipients guided by the viral doubling time in the blood

“…The use of this criterion for the inception of antiviral therapy would have resulted in a number of patients being treated~1 week earlier. 7 We hypothesized that this could possibly result in a reduction in the number of days on treatment. Here, we report on our experience with this therapeutic strategy, already in use at our center for 1 year.…”

“…The most relevant characteristics of the patients are shown in Table 1. CMV DNA load monitoring in plasma was performed as previously indicated, 3,5,7 using the new RealTime CMV PCR (Abbott Molecular, Des Plaines, IL, USA), whose limit of detection and quantification is 20 copies/mL (95% confidence interval). 8,9 Antiviral therapy with valganciclovir either at conventional doses (900 mg/12 h) or at reduced doses (450 mg/12 h) in patients meeting one or more of the following criteria: o 50 kg body weight, reduction of the glomerular filtrate ⩽ 60 mL/min per 1.73 m 2 , o1000 neutrophils/μL or o 50 000 platelets/μL, was initiated when the CMV dt was ⩽ 2.0 days, or alternatively when the plasma CMV DNA load reached levels of 41000 copies/mL, whichever occurred first.…”

“…The CMV dts were calculated using the CMV DNA load values measured in the first two positive QRT-PCR results (Table 2). 7,10 Antiviral therapy was interrupted upon the first undetectable (o 20 copies/mL) QRT-PCR result. 11 Out of the 67 episodes of active CMV infection, 27 (40%) were initial episodes, occurring at a median of 26 days (range, 5-56 days) following Allo-SCT, and 40 (60%) were recurrent episodes, developing at a median of 167 days (range, 32-723 days) after Allo-SCT.…”

Re-examining the relationship between active cytomegalovirus (CMV) infection and acute graft-versus-host disease in allogeneic stem cell transplant recipients in the era of real-time PCR CMV assays

“…The use of methods for CMV surveillance displaying different sensitivities (pp65 antigenemia assay (AG) vs. real-time PCR assays) may account in part for these discrepancies [6]. In this single-center retrospective study, we re-examined this potential association using highly sensitive real-time PCR assays (limit of detection: approximately 20 copies/ml- [6][7][8]) (CMV PCR Kit and the New CMV RealTime PCR assay; Abbott Molecular, Des Plaines, IL, USA) in plasma specimens. We included 92 nonconsecutive patients undergoing Allo-SCT (January 2010-August 2014) for hematological malignancy.…”