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Surveillance for adenovirus DNAemia early after transplantation in adult recipients of unrelated-donor allogeneic stem cell transplants in the absence of clinically suspected infection

Bone Marrow Transplantation volume 46, pages 1484–1486 (2011)Cite this article

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Disseminated adenovirus (AdV) disease is being increasingly recognized as a relevant cause of morbidity and mortality in patients undergoing allogeneic stem cell transplantation (allo-SCT), particularly in children less than 5 years old receiving haploidentical grafts.1 The incidence of severe AdV disease has been shown to be substantially lower in adult allo-SCT patients, but it is frequently associated with a poor clinical outcome.1 Detection of AdV DNA in peripheral blood may precede by several days or weeks the diagnosis of clinically overt AdV disease.1, 2, 3 In this context, sustained high-level or increasing AdV DNAemia appear to be specific and sensitive markers of progression of AdV infection to disseminated disease, both in pediatric and adult recipients.3 Thus, early detection of AdV DNAemia may allow timely implementation of antiviral therapy and/or prompt tapering of immunosuppression, which may potentially minimize the risk of occurrence of disseminated infection.1, 4 To date, nevertheless, no consensus exists on whether systematic monitoring for AdV DNAemia should be performed in adult allo-SCT recipients.4 We read with great interest a recently published article by Öhrmalm et al.,5 in which the above issue was addressed. Transient plasma low-level AdV DNAemia (<500 copies per mL) was detected in two out of 77 adult allo-SCT recipients (at days 82 and 118) by a real-time PCR (sensitivity 5 copies per reaction), in the absence of clinical signs of AdV infection. Around 40% of patients in their series were, nevertheless, at an intermediate risk for disseminated AdV infection, according to recently published risk-stratification criteria.4 The authors concluded that their data would not support routine AdV screening (in blood) in an unselected population of adult patients undergoing allo-SCT, although the idea of AdV screening was not conclusively dismissed. As the authors stated, it would be logical to identify what group of patients would potentially benefit from AdV DNAemia surveillance before establishing specific recommendations on this issue. We wish to add our experience in this context. In this work, we retrospectively investigated the incidence of AdV DNAemia during the first 100 days after transplantation in a selected cohort of adult allo-SCT recipients at high risk for disseminated AdV disease (recipients of unrelated-donor, HLA-mismatched or umbilical cord blood grafts, treatment with T-cell depleting agents, such as antithymocyte globulin or GvHD requiring the use of systemic corticosteroids).4 A total of 44 patients undergoing unrelated-donor allo-SCT at four university hospitals in Spain between February 2006 and 2009, and who had frozen plasma specimens (three or more) available for further testing were included in the study and retrospectively examined for the presence of plasma AdV DNAemia. Relevant clinical characteristics of the patients are summarized in Table 1. Of note that: (i) active CMV infection (plasma CMV DNAemia, pp65 antigenemia or both) was detected in almost 80% of patients at a median of 33.5 days after transplantation (range, 12–60 days). All episodes were preemptively treated with (val)ganciclovir (median duration of treatments, 27 days; range, 14–>100 days); only one patient received prophylactic valganciclovir; (ii) GvHD requiring the use of systemic corticosteroid therapy developed in almost one-third of the patients at a median of 46 days after transplantation (range, 19–90 days).

Table 1 Demographic and clinical data of the patients
Full size table

All but one of the patients included in the study had AdV-specific IgGs before transplantation, as determined by a commercial EIA assay (Adenovirus ELISA IgG/IgM, Vircell S.L., Granada, Spain). A total of 293 plasma samples (a median of 6 samples per patient; range, 3–17 samples) obtained within a median of 13 days (range, 0–27 days) to a median of 102 days (range, 87–118 days) after transplantation were analyzed. Total DNA was extracted from 200 μL of plasma by using the Biorobot EZ-1 (Qiagen, Valencia, CA, USA). Screening for AdV DNAemia was performed by a commercially available real-time PCR Kit (Adenovirus R-Gene Kit; Argene Inc., Massapequa, NY, USA), which targets the AdV hexon gene, and is validated for detection of serotypes 1–52. The sensitivity of the assay is 10 copies per reaction. A recent study has validated the use of this assay for clinical purposes in HSCT recipients.6 All plasma samples tested negative for the presence of AdV DNA. Thirty-eight patients had no clinically suspected AdV infection during the study period. Six patients developed hemorrhagic cystitis, but in no case was shown to be caused by AdV infection.

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References

  1. Echavarria M . Adenoviruses in immunocompromised hosts. Clin Microbiol Rev 2008; 21: 704–715.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Lion T, Baumgartinger R, Watzinger F, Matthes-Martin S, Suda M, Preuner S et al. Molecular monitoring of adenovirus in peripheral blood after allogeneic bone marrow transplantation permits early diagnosis of disseminated disease. Blood 2003; 102: 1114–1120.

    Article  CAS  PubMed  Google Scholar 

  3. Erard V, Huang M-L, Ferrenberg J, Nguy L, Steven-Ayers TL, Hackman RC et al. Quantitative real-time polymerase chain reaction for detection of adenovirus after T cell-replete hematopoietic cell transplantation: viral load as a marker of invasive disease. Clin Infect Dis 2007; 45: 958–965.

    Article  CAS  PubMed  Google Scholar 

  4. Zaia J, Baden L, Boeckh MJ, Chakrabarti S, Einsele H, Ljungman P et al. Viral disease prevention after hematopoietic cell transplantation. Bone Marrow Transplant 2009; 44: 471–482.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Öhrmalm L, Lindblom A, Omar H, Norbeck O, Gustafson I, Lewensohn-Fuchs I et al. Evaluation of a surveillance strategy for early detection of adenovirus by PCR of peripheral blood in hematopoietic SCT recipients: incidence and outcome. Bone Marrow Transplant 2011; 46: 267–272.

    Article  PubMed  Google Scholar 

  6. Jeulin H, Salmon A, Bordigoni P, Venard V . Comparison of in-house real-time quantitative PCR to the Adenovirus R-Gene kit for determination of adenovirus load in clinical samples. J Clin Microbiol 2010; 48: 3132–3137.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Kalpoe JS, van der Heiden J, Barge RM, Houtzager S, Lankester AC, van Tol MJD et al. Assessment of disseminated adenovirus infections using quantitative plasma PCR in adult allogeneic stem cell transplant recipients receiving reduced intensity or myeloablative conditioning. Eur J Haematol 2007; 78: 314–321.

    Article  CAS  PubMed  Google Scholar 

  8. Bruno B, Gooley T, Hackman RC, David C, Corey L, Boeckh M . Adenovirus infection in hematopoietic stem cell transplantation: effect of ganciclovir and impact on survival. Biol Blood Marrow Transplant 2003; 9: 341–352.

    Article  PubMed  Google Scholar 

  9. Gustafson I, Lindblom A, Yun Z, Omar H, Engstrom L, Lewensohn-Fuchs I et al. Quantification of adenovirus DNA in unrelated donor hematopoietic stem cell transplant recipients. J Clin Virol 2008; 43: 79–85.

    Article  CAS  PubMed  Google Scholar 

  10. Lion T, Kosulin K, Lanlinger C, Rauch M, Preuner S, Jugovic D et al. Monitoring of adenovirus load in stool by real-time PCR permits early detection of impending invasive infection in patients after allogeneic stem cell transplantation. Leukemia 2010; 24: 706–714.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Microbiology Service, Hospital Clínico Universitario, Valencia, Spain

    B Muñoz-Cobo, E Costa, D Bravo & D Navarro

  2. Hematology and Medical Oncology Service, Hospital Clínico Universitario, Valencia, Spain

    C Solano, M J Remigia, I Benet & J C Hernández-Boluda

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

    C Solano

  4. Hematology Service, Hospital Morales Meseguer, Murcia, Spain

    J Nieto

  5. Hematology Service, Hospital de La Princesa, Madrid, Spain

    R de la Cámara & A Garcia-Noblejas

  6. Hematology Service, Hospital Ramón y Cajal, Madrid, Spain

    J López

  7. 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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Muñoz-Cobo, B., Solano, C., Nieto, J. et al. Surveillance for adenovirus DNAemia early after transplantation in adult recipients of unrelated-donor allogeneic stem cell transplants in the absence of clinically suspected infection. Bone Marrow Transplant 46, 1484–1486 (2011). https://doi.org/10.1038/bmt.2010.322

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