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.

  • Letter to the Editor
  • Published:

Monitoring EBV DNA in saliva for early diagnosis of EBV reactivation in solid tumour patients after allogeneic haematopoietic SCT

Bone Marrow Transplantation volume 44, pages 259–261 (2009)Cite this article

The EBV shedding and transmission occur probably through saliva after replication in the oropharyngeal epithelium.1, 2 We have explored the possibility of an EBV survey using RQ–PCR in the saliva of solid tumour patients treated with allogeneic SCT. We assumed that in this new patient group, the reduced-intensity conditioning used would cause less preparation-related damage of cells with high turnover in the oropharynx. In addition, reduced-intensity conditioning might lead to an early immune recovery and also decrease the risk of lymphoproliferative disease and lymphoma.

Twenty patients, median age 55.5 years, with metastatic solid cancer underwent allogeneic SCT as adjuvant therapy (Table 1). The control group consisted of 10 age- and sex-matched healthy individuals. All, but one donor, was EBV positive by serology. Patients and control persons gave their informed consent to participate in this study, which was approved by the local ethics committee. Conditioning was either non-myeloablative (n=4) or of reduced-intensity (n=16) using fludarabine and 2 Gy TBI or CY, and in patients with a matched unrelated donor (MUD), ATG of 4 mg/kg (Table 1).3, 4 Complete donor chimerism was defined when >95% of peripheral blood CD3+ cells were of donor origin.5 The EBV genome load in prospectively collected saliva (2 ml; n=175) and peripheral blood (20 ml EDTA; n=177) samples was measured using RQ–PCR.6

Table 1 Patient characteristics
Full size table

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1

References

  1. Masucci MG, Ernberg I . Epstein–Barr virus: adaptation to a life within the immune system. Trends Microbiol 1994; 2: 125–130.

    Article  CAS  PubMed  Google Scholar 

  2. Young LS, Rickinson AB . Epstein–Barr virus: 40 years on. Nat Rev Cancer 2004; 4: 757–768.

    Article  CAS  PubMed  Google Scholar 

  3. Hentschke P, Barkholt L, Uzunel M, Mattsson J, Wersäll P, Pisa P et al. Low-intensity conditioning and hematopoietic stem cell transplantation in patients with renal and colon carcinoma. Bone Marrow Transplant 2003; 31: 253–261.

    Article  CAS  Google Scholar 

  4. Le Blanc K, Remberger M, Uzunel M, Mattsson J, Barkholt L, Ringdén O . A comparison of nonmyeloablative and reduced-intensity conditioning for allogeneic stem-cell transplantation. Transplantation 2004; 78: 1014–1020.

    Article  CAS  PubMed  Google Scholar 

  5. Zetterquist H, Mattsson J, Uzunel M, Näsman-Björk I, Svenberg P, Tammik L et al. Mixed chimerism in the B cell lineage is a rapid and sensitive indicator of minimal residual disease in bone marrow transplant recipients with pre-B cell acute lymphoblastic leukemia. Bone Marrow Transplant 2000; 25: 843–851.

    Article  CAS  PubMed  Google Scholar 

  6. Enbom M, Strand A, Falk KI, Linde A . Detection of Epstein–Barr virus, but not human herpes virus 8, DNA in cervical secretions from Swedish women by real-time polymerase chain reaction. Sex Transm Dis 2001; 28: 300–306.

    Article  CAS  PubMed  Google Scholar 

  7. Sundin M, Le Blanc K, Ringden O, Barkholt L, Omazic B, Lergin C et al. The role of HLA mismatch, splenectomy and recipient Epstein–Barr virus seronegativity as risk factors in post-transplant lymphoproliferative disorder following allogeneic hematopoietic stem cell transplantation. Haematologica 2006; 91: 1059–1067.

    PubMed  Google Scholar 

  8. Hislop AD, Kuo M, Drake-Lee AB, Akbar AN, Bergler W, Hammerschmitt N et al. Tonsillar homing of Epstein–Barr virus-specific CD8+ T cells and the virus-host balance. J Clin Invest 2005; 115: 2546–2555.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Hentschke P, Omazic B, Mattsson J, Näsman-Björk I, Lundkvist I, Gigliotti D et al. T-cell receptor Vbeta repertoire after myeloablative and reduced intensity conditioning allogeneic haematopoietic stem cell transplantation. Scand J Immunol 2005; 61: 285–294.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We are indebted to the staff at the Centre for Allogeneic Stem Cell Transplantation, and we thank the Departments of Haematology and Paediatrics for their compassionate and competent patient care.

Author information

Authors and Affiliations

  1. Division of Clinical Immunology and Transfusion Medicine, Department of Laboratory Medicine, Stockholm, Sweden

    A Mollbrink & L Barkholt

  2. Department of Microbiology, Tumor and Cell Biology, Stockholm, Sweden

    K I Falk & A Linde

  3. Swedish Institute for Infectious Disease Control, Stockholm, Sweden

    K I Falk & A Linde

  4. Centre for Allogeneic Stem Cell Transplantation, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden

    L Barkholt

Authors
  1. A Mollbrink
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K I Falk
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A Linde
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. L Barkholt
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to L Barkholt.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mollbrink, A., Falk, K., Linde, A. et al. Monitoring EBV DNA in saliva for early diagnosis of EBV reactivation in solid tumour patients after allogeneic haematopoietic SCT. Bone Marrow Transplant 44, 259–261 (2009). https://doi.org/10.1038/bmt.2009.5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2009.5

Search

Advanced search

Quick links