Human cytomegalovirus (HCMV) replication kinetics in stem cell transplant recipients following anti-HCMV therapy

Buyck, Hubertus; Griffiths, Paul; Emery, Vincent C.

doi:10.1016/j.jcv.2010.06.018

Cited by 25 publications

(29 citation statements)

References 38 publications

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“…This high sensitivity will allow more precise assessment of the kinetics of viral replication for (i) early detection of individuals with short CMV doubling time and (ii) better determination of CMV half-life in patients receiving antiviral therapy. These measures might be useful in adjustment of the duration of treatment (3,22,25). Despite a good overall correlation among concordant positive results, differences above 0.5 log 10 copies/ml were observed for 36.9% of these samples.…”

Section: Discussionmentioning

confidence: 96%

Fully Automated Quantification of Cytomegalovirus (CMV) in Whole Blood with the New Sensitive Abbott RealTi m e CMV Assay in the Era of the CMV International Standard

et al. 2013

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f Fully standardized reproducible and sensitive quantification assays for cytomegalovirus (CMV) are needed to better define thresholds for antiviral therapy initiation and interruption. We evaluated the newly released Abbott RealTime CMV assay for CMV quantification in whole blood (WB) that includes automated extraction and amplification (m2000 RealTime system). Sensitivity, accuracy, linearity, and intra-and interassay variability were validated in a WB matrix using Quality Control for Molecular Diagnostics (QCMD) panels and the WHO international standard (IS). The intra-and interassay coefficients of variation were 1.37% and 2.09% at 5 log 10 copies/ml and 2.41% and 3.80% at 3 log 10 copies/ml, respectively. According to expected values for the QCMD and Abbott RealTime CMV methods, the lower limits of quantification were 104 and <50 copies/ml, respectively. The conversion factor between international units and copies (2.18), determined from serial dilutions of the WHO IS in WB, was significantly different from the factor provided by the manufacturer (1.56) (P ‫؍‬ 0.001). Results from 302 clinical samples were compared with those from the Qiagen artus CMV assay on the same m2000 RealTime system. The two assays provided highly concordant results (concordance correlation coefficient, 0.92), but the Abbott RealTime CMV assay detected and quantified, respectively, 20.6% and 47.8% more samples than the Qiagen/artus CMV assay. The sensitivity and reproducibility of the results, along with the automation, fulfilled the quality requirements for implementation of the Abbott RealTime CMV assay in clinical settings. Our results highlight the need for careful validation of conversion factors provided by the manufacturers for the WHO IS in WB to allow future comparison of results obtained with different assays.

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Section: Discussionmentioning

confidence: 96%

Fully Automated Quantification of Cytomegalovirus (CMV) in Whole Blood with the New Sensitive Abbott RealTi m e CMV Assay in the Era of the CMV International Standard

et al. 2013

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“…However, we assume that it may be rare that 1 week of GCV use results in the emergence of resistance, because prolonged GCV exposure with ongoing high viral replication and impaired host defenses is usually associated with the emergence of GCV-resistant strains (10,12,14). Indeed, the previous studies showed that no GCV-resistant strain was detected in patients with rising CMV PCR levels during 1 week of GCV therapy (4,9,10).…”

Section: Discussionmentioning

confidence: 96%

Paradoxical Rising Cytomegalovirus Antigenemia during Preemptive Ganciclovir Therapy in Hematopoietic Stem Cell Transplant Recipients: Incidence, Risk Factors, and Clinical Outcomes

et al. 2011

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Preemptive ganciclovir (GCV) therapy is adopted increasingly in hematopoietic stem cell transplant (HCT) recipients, but occasional cases of increasing cytomegalovirus (CMV) antigenemia levels occur during preemptive GCV therapy. This prospective study investigated the incidence, risk factors, and clinical outcomes of paradoxical responses during GCV therapy. Adult patients receiving allogeneic HCTs during a 24-month period were enrolled. Patients were prospectively monitored for CMV antigenemia once a week until 3 months after engraftment. Paradoxical responders were defined as patients exhibiting CMV antigenemia levels elevated from the baseline after the first week of preemptive GCV therapy. Of 252 HCT recipients, 97 (38%) received preemptive GCV therapy due to CMV infection. Of these 97 patients, 23 (24%) were classified as paradoxical responders. Risk factors for paradoxical response were a low white blood cell ( Cytomegalovirus (CMV) diseases, including pneumonitis, gastroenteritis, retinitis, and encephalitis, are among the most important causes of morbidity and mortality in patients who undergo allogeneic hematopoietic stem cell transplantation (HCT) (3,17,18). Recently, the value of noninvasive diagnostic methods such as CMV blood antigenemia assay (1) and CMV DNA assay by PCR (5) in identifying candidates for preemptive therapy after HCT has been demonstrated. While preemptive ganciclovir (GCV) therapy based on the CMV blood antigenemia assay is being adopted increasingly for HCT recipients (2), occasional cases show increasing CMV antigenemia levels during preemptive GCV therapy. However, there are limited data on the clinical characteristics and outcomes of these paradoxical responders to GCV (7-9, 15). We therefore investigated the incidence of and risk factors for paradoxical responses among HCT patients during preemptive GCV therapy and their clinical outcomes.

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“…However, rather than time to resolution of viremia, delayed virologic response was defined as an increase in CMV DNA levels early after treatment initiation. While one study reported an association between higher viral loads at the initiation of therapy and a delayed virologic response, the other did not(14, 23). …”

Section: Discussionmentioning

confidence: 97%

Cytomegalovirus load at treatment initiation is predictive of time to resolution of viremia and duration of therapy in hematopoietic cell transplant recipients

Waggoner

Pinsky

2015

Journal of Clinical Virology

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Background Preemptive antiviral therapy relies on viral load measurements and is the mainstay of cytomegalovirus (CMV) prevention in hematopoietic cell transplant (HCT) recipients. However, optimal CMV levels for the initiation of preemptive therapy have not been defined. Objectives To evaluate the relationship between plasma CMV DNA levels at initiation of preemptive therapy with time to resolution of viremia and duration of treatment. Study Design Retrospective analysis of HCT recipients undergoing serial CMV PCR testing between June 2011 and June 2014 was performed. Results 221 HCT recipients underwent preemptive therapy for 305 episodes of CMV viremia. Median time to resolution was shorter when treatment was initiated at lower CMV levels (15 days at 135-440 international units (IU)/mL, 18 days at 441-1000 IU/mL, and 21 days at >1000 IU/mL, P <.001). Prolonged viremia lasting >30 days occurred less frequently when treatment was initiated at 135-440 IU/mL compared to 441-1000 IU/mL and >1000 IU/mL (1%, 15%, 24%, P<.001). Median treatment duration was also shorter in the lower viral load groups (28, 34, 37 days, P <.001). Conclusion Initiation of preemptive therapy at low CMV levels was associated with shorter episodes of viremia and courses of antiviral therapy. These data support the utility of initiating preemptive CMV therapy at viral loads as low as 135 IU/mL in HCT recipients.

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Human cytomegalovirus (HCMV) replication kinetics in stem cell transplant recipients following anti-HCMV therapy

Cited by 25 publications

References 38 publications

Fully Automated Quantification of Cytomegalovirus (CMV) in Whole Blood with the New Sensitive Abbott RealTi m e CMV Assay in the Era of the CMV International Standard

Fully Automated Quantification of Cytomegalovirus (CMV) in Whole Blood with the New Sensitive Abbott RealTi m e CMV Assay in the Era of the CMV International Standard

Paradoxical Rising Cytomegalovirus Antigenemia during Preemptive Ganciclovir Therapy in Hematopoietic Stem Cell Transplant Recipients: Incidence, Risk Factors, and Clinical Outcomes

Cytomegalovirus load at treatment initiation is predictive of time to resolution of viremia and duration of therapy in hematopoietic cell transplant recipients

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