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Pre-emptive antiviral therapy for active CMV infection in adult allo-SCT patients guided by plasma CMV DNAemia quantitation using a real-time PCR assay: clinical experience at a single center

Bone Marrow Transplantation volume 48, pages 1010–1012 (2013)Cite this article

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Pre-emptive antiviral therapy is the first-choice strategy for the prevention of CMV end-organ disease in the allo-SCT setting.1 In recent years, most institutions, including ours, have switched from the pp65 antigenemia assay (AG) to quantitative real-time PCR methods (QRT–PCR) for the guidance of pre-emptive antiviral therapy. Nevertheless, there are scarce published data as to how both strategies compare in terms of their clinical efficacy.2, 3, 4, 5 Although the criteria for initiation and cessation of pre-emptive antiviral therapy guided by the AG assay are rather standard across transplantation centers, there are no consensus criteria as to how active CMV infection should be managed in the QRT–PCR era.1 In fact, no validated CMV DNA load threshold (in either whole blood or plasma) exists for the inception of antiviral therapy, nor has a consensus been reached as to when antiviral treatment should be stopped (first negative QRT–PCR result/second negative QRT–PCR result/decrease of CMV DNA load below the cutoff for initiation of pre-emptive antiviral therapy). We retrospectively reviewed clinical and virological data from 147 consecutive patients who underwent T cell-replete allo-SCT at our center between January 2006 and May 2012. Until April 2010 (group I; n=90), CMV surveillance was performed in parallel by the AG assay and by a plasma real-time PCR assay (Abbott CMV PCR Kit, Abbott Diagnostics, Des Plaines, IL, USA).6 In this group, pre-emptive therapy was initiated upon a positive AG assay (⩾1 positive cell/200 000 polymorphonuclear leukocytes) and stopped upon two consecutive negative results after a minimum of 2 weeks of treatment, as previously described.6 Since May 2010 (group II; n=57), virological monitoring was exclusively performed by QRT–PCR, and pre-emptive therapy was initiated upon a plasma CMV DNAemia threshold level of 500 CMV DNA copies/mL and was discontinued after two consecutive PCR-negative (undetectable) results, after a minimum of 2 weeks of treatment. Virological monitoring was performed twice a week in the presence of active CMV infection and once a week otherwise (until day 120 after allo-SCT, and at each patient visit afterwards). Only episodes occurring during the 1st year after allo-ST were taken into consideration for the analyses described herein. Diagnosis and treatment of CMV end-organ disease was done following consensus criteria.7 Active CMV infection was defined by a positive QRT–PCR or AG test (in episodes with negative PCR results). A recurrent episode of active CMV infection was that occurring at least 15 days after clearance (first negative PCR result) of the preceding episode. Type A episodes were those in which plasma CMV DNA load decreased upon inception of antiviral therapy, until clearance. Type B episodes were those in which rising levels of CMV DNAemia (increases ⩾five-fold) were demonstrated after the implementation of antiviral therapy.8

As shown in Table 1, the demographic and clinical characteristics of patients in both groups were not significantly different. As shown in Table 2, the incidence rate of episodes of active CMV infection and that of recurrent episodes occurred more frequently in patients in group I than in those in group II, though statistical significance was not reached. This was most likely due to the different length of the follow-up period for patients in both groups.

Table 1 Demographic and clinical data of patients guided with the pp65 antigenemia assay or with a real-time PCR assay
Full size table
Table 2 Incidence of features of active CMV infection in patients guided with the pp65 antigenemia assay (AG) or with a real-time PCR assay (QRT–PCR)
Full size table

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Acknowledgements

We thank Julia García and Mónica Reig for their technical assistance. This research was supported by a grant (09/1117) from FIS (Fondo de Investigaciones Sanitarias, Ministerio de Sanidad y Consumo, Spain). PA is a research fellow of the Asociación Española contra el Cáncer (AECC).

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Authors and Affiliations

  1. Hematology and Medical Oncology Service, Hospital Clínico Universitario, Institute for Research INCLIVA, Valencia, Spain

    C Solano, M J Remigia, P Amat, I Benet & J Montoro

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

    C Solano

  3. Microbiology Service, Hospital Clínico Universitario, Institute for Research INCLIVA, Valencia, Spain

    B Muñoz-Cobo, E Giménez, M A Clari, D Bravo & D Navarro

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

    D Navarro

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Solano, C., Muñoz-Cobo, B., Giménez, E. et al. Pre-emptive antiviral therapy for active CMV infection in adult allo-SCT patients guided by plasma CMV DNAemia quantitation using a real-time PCR assay: clinical experience at a single center. Bone Marrow Transplant 48, 1010–1012 (2013). https://doi.org/10.1038/bmt.2012.286

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