Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Post-Transplant Events

Plasma HHV-6 viral load-guided preemptive therapy against HHV-6 encephalopathy after allogeneic stem cell transplantation: a prospective evaluation

Abstract

Human herpesvirus 6 (HHV-6) causes life-threatening encephalopathy in recipients of allogeneic SCT, but no consensus has been reached regarding appropriate preventive methods. This study evaluated a plasma HHV-6 viral load-guided preemptive approach against HHV-6-associated encephalopathy. Plasma real-time PCR assay was performed once a week. Among 29 patients, 19 developed positive plasma HHV-6 DNA. Median maximum plasma HHV-6 DNA was 4593.5 copies/ml plasma (range, 150.0–127 891.0 copies/ml plasma). In one of eight events with low-level HHV-6 DNA (defined as <1000 copies/ml plasma) and four of seven events with mid-level HHV-6 DNA (1000–9999.5 copies/ml plasma), HHV-6 loads in plasma subsequently continued increasing. Ganciclovir was administered against six of nine patients with high-level HHV-6 DNA (10 000 copies/ml plasma). High-level HHV-6 DNA resolved similarly in both groups with or without ganciclovir therapy. Among the nine patients with high-level HHV-6 DNA two developed encephalopathy. As encephalopathy developed before the detection of high-level HHV-6 DNA in plasma, these two patients had not received preemptive ganciclovir therapy. In conclusion, our preemptive approach against HHV-6-associated encephalopathy cannot prevent all cases of HHV-6 encephalopathy in SCT recipients due to the dynamic kinetics of plasma HHV-6 viral load.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Yoshikawa T, Ihira M, Ohashi M, Suga S, Asano Y, Miyazaki H et al. Correlation between HHV-6 infection and skin rash after allogeneic bone marrow transplantation. Bone Marrow Transplant 2001; 28: 77–81.

    Article  CAS  Google Scholar 

  2. Ljungman P, Wang FZ, Clark DA, Emery VC, Remberger M, Ringden O et al. High levels of human herpesvirus 6 DNA in peripheral blood leucocytes are correlated to platelet engraftment and disease in allogeneic stem cell transplant patients. Br J Haematol 2000; 111: 774–781.

    CAS  Google Scholar 

  3. Zerr DM, Corey L, Kim HW, Huang ML, Nguy L, Boeckh M . Clinical outcomes of human herpesvirus 6 reactivation after hematopoietic stem cell transplantation. Clin Infect Dis 2005; 40: 932–940.

    Article  Google Scholar 

  4. Ogata M, Kikuchi H, Satou T, Kawano R, Ikewaki J, Kohno K et al. Human herpesvirus 6 DNA load in plasma after allogeneic stem cell transplantation: incidence and clinical significance. J Infect Dis 2006; 193: 68–79.

    Article  CAS  Google Scholar 

  5. Drobyski WR, Knox KK, Majewski D, Carrigan DR . Brief report: fatal encephalitis due to variant B human herpesvirus-6 infection in a bone marrow-transplant recipient. N Engl J Med 1994; 330: 1356–1360.

    Article  CAS  Google Scholar 

  6. Wainwright MS, Martin PL, Morse RP, Lacaze M, Provenzale JM, Coleman RE et al. Human herpesvirus 6 limbic encephalitis after stem cell transplantation. Ann Neurol 2001; 50: 612–619.

    Article  CAS  Google Scholar 

  7. Zerr DM . Human herpesvirus 6 and central nervous system disease in hematopoietic cell transplantation. J Clin Virol 2006; 37: 52–56.

    Article  Google Scholar 

  8. Zerr DM . Human herpesvirus 6: a clinical update. Herpes 2006; 13: 20–24.

    Google Scholar 

  9. Yamane A, Mori T, Suzuki S, Mihara A, Yamazaki R, Aisa Y et al. Risk factors for developing human herpesvirus 6 (HHV-6) reactivation after allogeneic hematopoietic stem cell transplantation and its association with central nervous system disorders. Biol Blood Marrow Transplant 2007; 13: 100–106.

    Article  CAS  Google Scholar 

  10. Noguchi T, Mihara F, Yoshiura T, Togao O, Atsumi K, Matsuura T et al. MR imaging of human herpesvirus-6 encephalopathy after hematopoietic stem cell transplantation in adults. AJNR Am J Neuroradiol 2006; 27: 2191–2195.

    CAS  Google Scholar 

  11. Schmidt GM, Horak DA, Niland JC, Duncan SR, Forman SJ, Zaia JA . A randomized, controlled trial of prophylactic ganciclovir for cytomegalovirus pulmonary infection in recipients of allogeneic bone marrow transplants; The City of Hope-Stanford-Syntex CMV Study Group. N Engl J Med 1991; 324: 1005–1011.

    Article  CAS  Google Scholar 

  12. Boeckh M, Gooley TA, Myerson D, Cunningham T, Schoch G, Bowden RA . Cytomegalovirus pp65 antigenemia-guided early treatment with ganciclovir versus ganciclovir at engraftment after allogeneic marrow transplantation: a randomized double-blind study. Blood 1996; 88: 4063–4071.

    CAS  PubMed  Google Scholar 

  13. Rapaport D, Engelhard D, Tagger G, Or R, Frenkel N . Antiviral prophylaxis may prevent human herpesvirus-6 reactivation in bone marrow transplant recipients. Transpl Infect Dis 2002; 4: 10–16.

    Article  CAS  Google Scholar 

  14. Tokimasa S, Hara J, Osugi Y, Ohata H, Matsuda Y, Fujisaki H et al. Ganciclovir is effective for prophylaxis and treatment of human herpesvirus-6 in allogeneic stem cell trensplantation. Bone Marrow Transplant 2002; 29: 595–598.

    Article  CAS  Google Scholar 

  15. Sashihara J, Tanaka-Taya K, Tanaka S, Amo K, Miyagawa H, Hosoi G et al. High incidence of human herpesvirus 6 infection with a high viral load in cord blood stem cell transplant recipients. Blood 2002; 100: 2005–2011.

    CAS  Google Scholar 

  16. Matubara Y, Hori T, Morita R, Sakaguchi S, Uchiyama T . Delineation of immunoregulatory properties of adult T-cell leukemia cells. Int J Hematol 2006; 84: 63–69.

    Article  Google Scholar 

  17. Zerr DM, Gupta D, Huang ML, Carter R Corey L . Effect of antivirals on human herpesvirus 6 replication in hematopoietic stem cell transplant recipients. Clin Infect Dis 2002; 34: 309–317.

    Article  CAS  Google Scholar 

  18. Wang FZ, Linde A, Hagglund H, Testa M, Locasciulli A, Ljungman P . Human herpesvirus 6 DNA in cerebrospinal fluid specimens from allogeneic bone marrow transplant patients: does it have clinical significance? Clin Infect Dis 1999; 28: 562–568.

    Article  CAS  Google Scholar 

  19. Achour A, Boutolleau D, Slim A, Agut H, Gautheret-Dejean A . Human herpesvirus-6 (HHV-6) DNA in plasma reflects the presence of infected blood cells rather than circulating viral particles. J Clin Virol 2007; 38: 280–285.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported in part by grants-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to M Ogata.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ogata, M., Satou, T., Kawano, R. et al. Plasma HHV-6 viral load-guided preemptive therapy against HHV-6 encephalopathy after allogeneic stem cell transplantation: a prospective evaluation. Bone Marrow Transplant 41, 279–285 (2008). https://doi.org/10.1038/sj.bmt.1705907

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1705907

Keywords

This article is cited by

Search

Quick links