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Non-Hodgkin's Lymphoma

Unrelated bone marrow transplantation for Epstein–Barr virus-associated T/NK-cell lymphoproliferative disease

Summary:

Epstein–Barr virus (EBV)-associated T/NK-cell lymphoproliferative disease (LPD) has been linked to several different disorders, including chronic active EBV infection, EBV-associated hemophagocytic syndrome, hypersensitivity to mosquito bites, hydroa vacciniforme, aggressive NK-cell leukemia, and nasal/nasal-type NK-cell lymphoma. In most instances, these disorders are refractory to conventional treatments and have a poor prognosis. Here, we report a new treatment strategy for EBV-associated T/NK-cell LPD, consisting of immunochemotherapy, intensive combination chemotherapy, and stem cell transplantation. The five patients studied, two with T-cell and three with NK-cell LPD, lacked a human leukocyte antigen-matched, related donor, and therefore received bone marrow grafts from HLA-matched, unrelated donors. The preconditioning regimen consisted of total-body irradiation (12 Gy), etoposide (900 mg/m2), and cyclophosphamide (120 mg/kg) or melphalan (210 mg/m2). All patients had residual LPD by a quantitative PCR technique prior to transplantation. After unrelated bone marrow transplantation (UBMT), four of the five patients remain in continuous complete remission at a median of 19 months, without detectable EBV-DNA in peripheral blood. Thus, UBMT appears to be a reasonable option for the treatment of patients with EBV-associated T/NK-cell LPD. Detection of EBV-DNA by PCR offers an important tool for assessing minimal residual disease in patients with EBV-associated T/NK-cell LPD.

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References

  1. Cohen JI . Epstein–Barr virus infection. N Engl J Med 2000; 343: 481–492.

    Article  CAS  PubMed  Google Scholar 

  2. Kawa K . Epstein–Barr virus-associated diseases in humans. Int J Hematol 2000; 71: 108–117.

    CAS  PubMed  Google Scholar 

  3. Jones JF, Shurin S, Abramowsky C et al. T-cell lymphomas containing Epstein–Barr viral DNA in patients with chronic Epstein–Barr virus infections. N Engl J Med 1988; 318: 733–741.

    Article  CAS  PubMed  Google Scholar 

  4. Kawa-Ha K, Ishihara S, Ninomiya T et al. CD3-negative lymphoproliferative disease of granular lymphocytes containing Epstein–Barr viral DNA. J Clin Invest 1989; 84: 51–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Ishihara S, Ohshima K, Tokura Y et al. Hypersensitivity to mosquito bites conceals clonal lymphoproliferation of Epstein–Barr viral DNA-positive natural killer cells. Jpn J Cancer Res 1997; 88: 82–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Iwatsuki K, Xu Z, Takata M et al. The association of latent Epstein–Barr virus infection with hydroa vacciniforme. Br J Dermatol 1999; 140: 715–721.

    Article  CAS  PubMed  Google Scholar 

  7. Kawa K, Ishihara S, Okamura T et al. Chronic active Epstein–Barr virus infection and lymphoproliferative disease. Gann Monogr Cancer Res 1998; 45: 139–147.

    Google Scholar 

  8. Kawa K, Okamura T, Yagi K et al. Mosquito allergy and Epstein–Barr virus-associated T/NK-cell lymphoproliferative disease. Blood 2001; 98: 3173–3174.

    Article  CAS  PubMed  Google Scholar 

  9. Okamura T, Hatsukawa Y, Arai H et al. Blood stem-cell transplantation for chronic active Epstein–Barr virus with lymphoproliferation. Lancet 2000; 356: 223–224.

    Article  CAS  PubMed  Google Scholar 

  10. Hirai K, Hironaka K, Kawa-Ha K et al. Application of PCR to various clinical specimens for the detection of Epstein–Barr virus and its evaluation. Rinsho to uirusu 1994; 22: 320–326.

    Google Scholar 

  11. Kimura H, Morita M, Yabuta Y et al. Quantitative analysis of Epstein–Barr virus load by using a real-time PCR assay. J Clin Microbiol 1999; 37: 132–136.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Okamura T, Inoue M, Yasui M et al. Identification of the Epstein–Barr virus infected cell in chronic active EB-virus infection. Igaku no Ayumi 1998; 187: 689–690.

    CAS  Google Scholar 

  13. Raab-Traub N, Flynn K . The structure of the termini of the Epstein–Barr virus as a marker of clonal cellular proliferation. Cell 1986; 47: 883–889.

    Article  CAS  PubMed  Google Scholar 

  14. Yagita M, Iwakura H, Kishimoto T et al. Successful allogeneic stem cell transplantation from an unrelated donor for aggressive Epstein–Barr virus-associated clonal T-cell proliferation with hemophagocytosis. Int J Hematol 2001; 74: 451–454.

    Article  CAS  PubMed  Google Scholar 

  15. Nagler A, Rabinowitz R, Rosengolts-Rat J et al. Natural killer (NK) and T cell-associated surface marker expression following allogeneic and autologous bone marrow transplantation (BMT). J Hematother Stem Cell Res 2000; 9: 63–75.

    Article  CAS  PubMed  Google Scholar 

  16. Imashuku S . Advances in the management of hemophagocytic lymphohistiocytosis. Int J Hematol 2000; 72: 1–11.

    CAS  PubMed  Google Scholar 

  17. Cheung MM, Chan JK, Lau WH et al. Primary non-Hodgkin's lymphoma of the nose and nasopharynx: clinical features, tumor immunophenotype, and treatment outcome in 113 patients. J Clin Oncol 1998; 16: 70–77.

    Article  CAS  PubMed  Google Scholar 

  18. Kuzushima K, Yamamoto M, Kimura H et al. Establishment of anti-Epstein–Barr virus (EBV) cellular immunity by adoptive transfer of virus-specific cytotoxic T lymphocytes from an HLA-matched sibling to a patient with severe chronic active EBV infection. Clin Exp Immunol 1996; 103: 192–198.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Ohshima K, Suzumiya J, Ohga S et al. Integrated Epstein–Barr virus (EBV) and chromosomal abnormality in chronic active EBV infection. Int J Cancer 1997; 71: 943–947.

    Article  CAS  PubMed  Google Scholar 

  20. Rooney CM, Smith CA, Ng CY et al. Use of genemodified virus-specific T lymphocytes to control Epstein–Barr-virus-related lymphoproliferation. Lancet 1995; 345: 9–13.

    Article  CAS  PubMed  Google Scholar 

  21. Sasaki M, Matsue K, Takeuchi M et al. Successful treatment of disseminated nasal NK/T-cell lymphoma using double autologous peripheral blood stem cell transplantation. Int J Hematol 2000; 71: 75–78.

    CAS  PubMed  Google Scholar 

  22. Teshima T, Miyaji R, Fukuda M et al. Bone-marrow transplantation for Epstein–Barr-virus-associated natural killer cell-large granular lymphocyte leukaemia. Lancet 1996; 347: 1124.

    Article  CAS  PubMed  Google Scholar 

  23. Minegishi M, Ohashi Y, Kumaki S et al. Successful umbilical cord blood transplantation from an unrelated donor for a patient with Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis. Bone Marrow Transplant 2001; 27: 883–886.

    Article  CAS  PubMed  Google Scholar 

  24. Kimura H, Hoshino Y, Kanegane H et al. Clinical and virologic characteristics of chronic active Epstein–Barr virus infection. Blood 2001; 98: 280–286.

    Article  CAS  PubMed  Google Scholar 

  25. Maeda A, Wakiguchi H, Yokoyama W et al. Persistently high Epstein–Barr virus (EBV) loads in peripheral blood lymphocytes from patients with chronic active EBV infection. J Infect Dis 1999; 179: 1012–1015.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Dr Cliona M Rooney and Helen E Heslop, Center for Cell and Gene Therapy, Baylor College of Medicine, for critical reading of the manuscript.

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Okamura, T., Kishimoto, T., Inoue, M. et al. Unrelated bone marrow transplantation for Epstein–Barr virus-associated T/NK-cell lymphoproliferative disease. Bone Marrow Transplant 31, 105–111 (2003). https://doi.org/10.1038/sj.bmt.1703796

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