Correspondence | Published:

Transmission of chromosomally integrated human herpes virus-6A via haploidentical stem cell transplantation poses a risk for virus reactivation and associated complications

Bone Marrow Transplantation (2019) | Download Citation

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

References

  1. 1.

    AWMF. AWMF-­Leitlinie 025/016: Sichelzellkrankheit. In: AWMF: Cario, Holger; Grosse, Regine; Jarisch, Andrea; Lobitz, Stephan; Kulozik, Andreas; Kunz, Joachim, 2014.

  2. 2.

    Foell J, Pfirstinger B, Rehe K, Wolff D, Holler E, Corbacioglu S. Haploidentical stem cell transplantation with CD3(+)-/CD19(+)- depleted peripheral stem cells for patients with advanced stage sickle cell disease and no alternative donor: results of a pilot study. Bone Marrow Transpl. 2017;52:938–40. https://doi.org/10.1038/bmt.2017.49

  3. 3.

    Bolanos-Meade J, Fuchs EJ, Luznik L, Lanzkron SM, Gamper CJ, Jones RJ, et al. HLA-haploidentical bone marrow transplantation with posttransplant cyclophosphamide expands the donor pool for patients with sickle cell disease. Blood. 2012;120:4285–91. https://doi.org/10.1182/blood-2012-07-438408

  4. 4.

    Zerr DM. Human herpesvirus 6B in the transplant recipient: when to worry, when to act. J Pediatr Infect Dis Soc. 2018;7:S75–S78. https://doi.org/10.1093/jpids/piy111. Review

  5. 5.

    Greco R, Crucitti L, Noviello M, Racca S, Mannina D, Forcina A, et al. Human herpesvirus 6 infection following haploidentical transplantation: immune recovery and outcome. Biol Blood Marrow Transpl. 2016;22:2250–5. https://doi.org/10.1016/j.bbmt.2016.09.018

  6. 6.

    Ablashi D, Agut H, Alvarez-Lafuente R, Clark DA, Dewhurst S, DiLuca D, et al. Classification of HHV-6A and HHV-6B as distinct viruses. Arch Virol. 2014;159:863–70. https://doi.org/10.1007/s00705-013-1902-5

  7. 7.

    Dominguez G, Dambaugh TR, Stamey FR, Dewhurst S, Inoue N, Pellett PE. Human herpesvirus 6B genome sequence: coding content and comparison with human herpesvirus 6A. J Virol. 1999;73:8040–52.

  8. 8.

    Hall CB, Long CE, Schnabel KC, Caserta MT, McIntyre KM, Costanzo MA, et al. Human herpesvirus-6 infection in children. A prospective study of complications and reactivation. N Engl J Med. 1994;331:432–8. https://doi.org/10.1056/NEJM199408183310703

  9. 9.

    Osterrieder N, Wallaschek N, Kaufer BB. Herpesvirus genome integration into telomeric repeats of host cell chromosomes. Annu Rev Virol. 2014;1:215–35. https://doi.org/10.1146/annurev-virology-031413-085422

  10. 10.

    Endo A, Watanabe K, Ohye T, Suzuki K, Matsubara T, Shimizu N, et al. Molecular and virological evidence of viral activation from chromosomally integrated human herpesvirus 6A in a patient with X-linked severe combined immunodeficiency. Clin Infect Dis. 2014;59:545–8. https://doi.org/10.1093/cid/ciu323

  11. 11.

    Winestone LE, Punn R, Tamaresis JS, Buckingham J, Pinsky BA, Waggoner JJ, et al. High human herpesvirus 6 viral load in pediatric allogeneic hematopoietic stem cell transplant patients is associated with detection in end organs and high mortality. Pediatr Transplant. 2018;22. https://doi.org/10.1111/petr.13084.

  12. 12.

    Phan TL, Carlin K, Ljungman P, Politikos I, Boussiotis V, Boeckh M, et al. Human herpesvirus-6B reactivation is a risk factor for grades II to IV acute graft-versus-host disease after hematopoietic stem cell transplantation: a systematic review and meta-analysis. Biol Blood Marrow Transpl. 2018;24:2324–36. https://doi.org/10.1016/j.bbmt.2018.04.021

  13. 13.

    Ogata M, Fukada T, Teshima T. Human herpesvirus-6 encephalitis after allogeneic hematopoietic cell transplantation: what we do and do not know. Bone Marrow Transpl. 2015;50:1030–6. https://doi.org/10.1038/bmt.2015.76.

  14. 14.

    Bonnafous P, Marlet J, Bouvet D, Salame E, Tellier AC, Guyetant S, et al. Fatal outcome after reactivation of inherited chromosomally integrated HHV-6A (iciHHV-6A) transmitted through liver transplantation. Am J Transpl. 2018;18:1548–51. https://doi.org/10.1111/ajt.14657

  15. 15.

    Prichard MN, Whitley RJ. The development of new therapies for human herpesvirus 6. Curr Opin Virol. 2014;9:148–53. https://doi.org/10.1016/j.coviro.2014.09.019

  16. 16.

    Tzannou I, Papadopoulou A, Naik S, Leung K, Martinez CA, Ramos CA, et al. Off-the-shelf virus-specific T cells to treat BK virus, human herpesvirus 6, cytomegalovirus, Epstein-Barr virus, and adenovirus infections after allogeneic hematopoietic stem-cell transplantation. J Clin Oncol. 2017;35:3547–57. https://doi.org/10.1200/JCO.2017.73.0655

Download references

Acknowledgements

L.O. and A.K. are participants in the BIH‐Charité Clinician Scientist Program funded by the Charité – Universitätsmedizin Berlin and the Berliner Institut für Gesundheitsforschung (BIH). This work was supported by a grant to L.O. from Bild Hilft e.V. – Ein Herz für Kinder and by the HHV-6 Foundation, who provided the anti-gp82/105 antibody. The anti-IE-1 antibody was kindly provided by L. Flamand and colleagues from the Laval University (Sainte-Foy, Quebec, Canada). We thank Kathy Astrahantseff for proofreading of the manuscript.

Author information

Author notes

  1. These authors contributed equally: Lena Oevermann, Cosima Zimmermann

Affiliations

  1. Department of Pediatric Hematology and Oncology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany

    • Lena Oevermann
    • , Sebastian Voigt
    • , Annette Künkele
    • , Angelika Eggert
    • , Johannes H. Schulte
    •  & Hedwig E. Deubzer
  2. Berliner Institut für Gesundheitsforschung (BIH), Anna-Louisa-Karsch-Strasse 2, 10178, Berlin, Germany

    • Lena Oevermann
    • , Annette Künkele
    • , Angelika Eggert
    • , Johannes H. Schulte
    •  & Hedwig E. Deubzer
  3. German Cancer Consortium (DKTK), Partner Site Berlin, Berlin, Germany

    • Lena Oevermann
    • , Angelika Eggert
    • , Johannes H. Schulte
    •  & Hedwig E. Deubzer
  4. German Cancer Research Center (DKFZ), Heidelberg, Germany

    • Lena Oevermann
    • , Angelika Eggert
    • , Johannes H. Schulte
    •  & Hedwig E. Deubzer
  5. Institute of Virology, Freie Universität Berlin, Robert-von-Ostertag-Strasse 7-13, 14163, Berlin, Germany

    • Cosima Zimmermann
    •  & Benedikt B. Kaufer
  6. Department of Infectious Diseases, Robert Koch Institute, Seestrasse 10, 13353, Berlin, Germany

    • Sebastian Voigt
  7. Department of Pediatric Hematology and Oncology, Kinderkrankenhaus, Amsterdamer Strasse 59, 50735, Köln, Germany

    • Stephan Lobitz
  8. Neuroblastoma Research Group, Experimental and Clinical Research Center (ECRC) of the Charité and the Max-Delbrück-Center for Molecular Medicine (MDC) in the Helmholtz Association, Lindenberger Weg, 8013125, Berlin, Germany

    • Hedwig E. Deubzer

Authors

  1. Search for Lena Oevermann in:

  2. Search for Cosima Zimmermann in:

  3. Search for Sebastian Voigt in:

  4. Search for Annette Künkele in:

  5. Search for Stephan Lobitz in:

  6. Search for Angelika Eggert in:

  7. Search for Johannes H. Schulte in:

  8. Search for Benedikt B. Kaufer in:

  9. Search for Hedwig E. Deubzer in:

Conflict of interest

The authors declare that they have no conflict of interest.

Corresponding author

Correspondence to Lena Oevermann.

Supplementary information

About this article

Publication history

Received

Revised

Accepted

Published

DOI

https://doi.org/10.1038/s41409-019-0530-4