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Refractory cytomegalovirus DNAemia after allogeneic hematopoietic stem cell transplantation: when should genotypic drug resistance testing be requested?

Bone Marrow Transplantation volume 53, pages 787–790 (2018)Cite this article

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Persisting cytomegalovirus (CMV) DNAemia in spite of appropriate antiviral therapy is a risk factor for CMV disease and non-relapse mortality in allogeneic hematopoietic stem cell transplant recipients (allo-HSCT) [1], and may be due to a lack of adequate expansion of functional CMV-specific T cells in response to viral replication (clinical resistance), to the emergence of antiviral resistant strains carrying specific point mutations or deletions within the sequence of the viral genes UL97, UL54 (virological resistance) or both [2, 3]. Currently, there is no consensus on when antiviral CMV resistance should be suspected and genotypic drug resistance testing be ordered. Several indicators reflecting therapeutic refractoriness have been proposed: [3,4,5] increase in CMV DNA load >20% (inter-assay coefficient of variation of the real-time PCR assays used) after 2 weeks of adequate treatment (Group 1), increase in CMV DNA load >0.5 log10 (Group 2) or >1 log10 (Group 3) after 2 weeks of treatment, and decrease in CMV DNA load <1 log10 after 2 (Group 4) or 2 (Group 5) weeks of treatment, in all categories with respect to CMV DNA load at the time of treatment initiation. In this study, refractory CMV DNAemia met one or more of the above criteria.

A total of 203 patients who underwent allo-HSCT between January 2010 and June 2017 were included in this retrospective observational study. The median age of patients was 55 years (range, 18-69 years). Plasma CMV DNA load was monitored as previously indicated [6], using the CMV PCR Kit or the CMV RealTime CMV PCR (both from Abbott Molecular, Des Plaines, IL, USA). Antiviral therapy with (val)ganciclovir or foscarnet at conventional doses was initiated when the plasma CMV DNA load reached levels of >1500 IU/ml, or when the CMV dt was ≤2.0 days, whatever occurred first (this latter strategy since May 2014) [7].

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Acknowledgements

Estela Giménez holds a Río Hortega research contract from the Carlos III Health Institute (Ref. CM16/00200). We thank José Miguel Molina for technical assistance. This research was supported in part by grants from FIS (Fondo de Investigaciones Sanitarias, Ministerio de Sanidad y Consumo, Spain) (12/01992) from AECC (Asociación Española Contra el Cáncer) for post-doctoral research (2013).

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Authors and Affiliations

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

    Carlos Solano, José Luis Piñana, Juan Carlos Hernández-Boluda & Ariadna Pérez

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

    Carlos Solano

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

    Alberto Talaya, Estela Giménez, Eliseo Albert & David Navarro

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

    David Navarro

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  1. Carlos Solano
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Correspondence to David Navarro.

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Solano, C., Talaya, A., Giménez, E. et al. Refractory cytomegalovirus DNAemia after allogeneic hematopoietic stem cell transplantation: when should genotypic drug resistance testing be requested?. Bone Marrow Transplant 53, 787–790 (2018). https://doi.org/10.1038/s41409-018-0191-8

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