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

Bone Marrow Transplantation volume 51, pages 718–721 (2016)Cite this article

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Preemptive antiviral therapy guided by quantitative real-time PCR assays (QRT-PCR) is currently the mainstay strategy for the prevention of CMV disease in allogeneic stem cell transplant (Allo-SCT) recipients.1, 2, 3, 4, 5 The main drawback of this strategy is drug-related toxicity due to overtreatment, whose magnitude ultimately depends upon the CMV DNA load threshold chosen for triggering the initiation of antiviral therapy.1, 2, 4 Emery et al.6 demonstrated the potential clinical value of kinetic analyses of CMV DNAemia in the management of CMV infection in transplant recipients. In this context, we recently showed that a CMV doubling time (dt) value of ⩽2 days in the blood compartment (plasma) predicted the eventual need for antiviral treatment using with a sensitivity of 100%. 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.

A total of 67 consecutive episodes of active CMV infection occurring in 43 Allo-SCT patients treated at the Hematology Unit of University Clinic Hospital between May 2014 and May 2015 were included in the current study. These patients underwent Allo-SCT between November 2012 and March 2015. The median age of patients was 56 years (range, 18–69 years). Written consent to participate in this study was obtained from the patients. 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: <50 kg body weight, reduction of the glomerular filtrate ⩽60 mL/min per 1.73 m2, <1000 neutrophils/μL or <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 >1000 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 (<20 copies/mL) QRT-PCR result.11

Table 1 Demographic and clinical characteristics of the patients
Full size table
Table 2 Virological and clinical parameters of episodes of active CMV infection treated preemptively with valganciclovir based upon the viral dt or a preestablished plasma CMV DNA load threshold
Full size table

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Acknowledgements

This research was supported in part by a grant (12/01992) from FIS (Fondo de Investigaciones Sanitarias, Ministerio de Sanidad y Consumo, Spain) and by private funds from Abbott Diagnostics.

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Authors and Affiliations

  1. Hematology and Medical Oncology Service, Hospital Clínico Universitario, Fundación INCLIVA, Valencia, Spain

    C Solano, J L Piñana & M Calabuig

  2. Department of Medicine, School of Medicine, University of Valencia, Valencia, Spain

    C Solano

  3. Microbiology Service, Hospital Clínico Universitario, Fundación INCLIVA, Valencia, Spain

    E Giménez, V Vinuesa, S Poujois, S Zaragoza & D Navarro

  4. Department of Microbiology, School of Medicine, University of Valencia, Valencia, Spain

    D Navarro

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Correspondence to D Navarro.

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DN has received honoraria from Abbott Diagnostics for participating in several conferences. All the remaining authors declare no conflict of interest.

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Solano, C., Giménez, E., Piñana, J. et al. Preemptive antiviral therapy for CMV infection in allogeneic stem cell transplant recipients guided by the viral doubling time in the blood. Bone Marrow Transplant 51, 718–721 (2016). https://doi.org/10.1038/bmt.2015.303

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