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Incidence and course of Epstein-Barr virus viremia after allogeneic hematopoietic stem cell transplant for adult-onset systemic chronic active Epstein-Barr virus disease

Bone Marrow Transplantation volume 58, pages 1397–1399 (2023)Cite this article

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Systemic chronic active Epstein-Barr virus disease (CAEBV) is a rare, rapidly progressive T/NK-cell lymphoproliferative disorder. Clonal proliferation of Epstein-Barr virus (EBV) infected T/NK cells results in sustained inflammation characterized by fever, lymphadenopathy, hepatosplenomegaly, and liver dysfunction [1, 2]. CAEBV is managed with cooling therapy (steroids and/or cyclosporine and/or etoposide), chemotherapy regimens for lymphoma, and allogeneic hematopoietic stem cell transplant (HSCT). Chemotherapy alone is inadequate, and HSCT is the only curative option[1, 3, 4]. Although EBV DNA load is important in diagnosing CAEBV [2], the utility of monitoring EBV DNA after HSCT is unknown, and information on the management of EBV viremia post-HSCT is scarce.

We retrospectively analyzed all adult (age ≥ 18) patients who fulfilled the diagnostic criteria of CAEBV [2] and underwent allogeneic HSCT at Hokkaido University Hospital from 2012 to 2022. During the study period, the method of EBV DNA determination in peripheral blood by quantitative polymerase chain reaction was changed twice, resulting in three different units. For standardization, all results were expressed in international units (IU)/mL. Appropriate conversion factors were applied to convert results expressed in copies/μg DNA to IU/mL (102.5 copies/μg DNA = 10,000 IU/mL) [5] and copies/mL to IU/mL (1 copy = 0.77 IU) [6]. Patients with active disease were those with persistent inflammation including fever, liver dysfunction, progressive skin lesions, vasculitis, or uveitis [2, 4]. Patients without these findings were classified as having inactive disease. Low EBV DNA load was defined as ≤100 IU/mL. High EBV viremia was defined as >10,000 IU/mL. Complete response (CR) was defined as complete resolution of disease activity, regardless of EBV DNA load. The study was carried out in accordance with the Declaration of Helsinki and approved by the Institutional Review Board.

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Fig. 1: Incidence and course of EBV viremia after allogeneic HSCT for CAEBV.

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

References

  1. Yamamoto M, Sato M, Onishi Y, Sasahara Y, Sano H, Masuko M, et al. Registry data analysis of hematopoietic stem cell transplantation on systemic chronic active Epstein-Barr virus infection patients in Japan. Am J Hematol. 2022;97:780–90. https://doi.org/10.1002/ajh.26544.

    Article  CAS  PubMed  Google Scholar 

  2. Kimura H, Ito Y, Kawabe S, Gotoh K, Takahashi Y, Kojima S, et al. EBV-associated T/NK-cell lymphoproliferative diseases in nonimmunocompromised hosts: prospective analysis of 108 cases. Blood 2012;119:673–86. https://doi.org/10.1182/blood-2011-10-381921.

    Article  CAS  PubMed  Google Scholar 

  3. Onishi Y, Onodera K, Fukuhara N, Kato H, Ichikawa S, Fujiwara T, et al. Unrelated cord blood transplantation for adult-onset EBV-associated T-cell and NK-cell lymphoproliferative disorders. Int J Hematol. 2022;115:873–81. https://doi.org/10.1007/s12185-022-03313-z.

    Article  CAS  PubMed  Google Scholar 

  4. Arai A, Sakashita C, Hirose C, Imadome KI, Yamamoto M, Jinta M, et al. Hematopoietic stem cell transplantation for adults with EBV-positive T- or NK-cell lymphoproliferative disorders: efficacy and predictive markers. Bone Marrow Transpl. 2016;51:879–82. https://doi.org/10.1038/bmt.2016.3.

    Article  CAS  Google Scholar 

  5. Kawada JI, Kamiya Y, Sawada A, Iwatsuki K, Izutsu K, Torii Y, et al. Viral DNA loads in various blood components of patients with Epstein-Barr virus-positive T-cell/natural killer cell lymphoproliferative diseases. J Infect Dis. 2019;220:1307–11. https://doi.org/10.1093/infdis/jiz315.

    Article  CAS  PubMed  Google Scholar 

  6. Bontems S, Boreux R, Capraro V, Huynen P, Descy J, Melin P, et al. Evaluation of the Abbott RealTime quantitative CMV and EBV assays using the maxCycle protocol in a laboratory automation context. J Virol Methods. 2019;270:137–45. https://doi.org/10.1016/j.jviromet.2019.05.007.

    Article  CAS  PubMed  Google Scholar 

  7. Styczynski J, van der Velden W, Fox CP, Engelhard D, de la Camara R, Cordonnier C, et al. Management of Epstein-Barr Virus infections and post-transplant lymphoproliferative disorders in patients after allogeneic hematopoietic stem cell transplantation: Sixth European Conference on Infections in Leukemia (ECIL-6) guidelines. Haematologica. 2016;101:803–11. https://doi.org/10.3324/haematol.2016.144428.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Wei N, Wang Y, Wang J, Wu L, Wang Z. Characteristics of Epstein-Barr virus reactivation after allogeneic haematopoietic stem cell transplantation in patients with chronic active Epstein-Barr virus disease: favorable responses to rituximab. Bone Marrow Transpl. 2021;56:1449–51. https://doi.org/10.1038/s41409-020-01193-7.

    Article  CAS  Google Scholar 

  9. Okuno Y, Murata T, Sato Y, Muramatsu H, Ito Y, Watanabe T, et al. Defective Epstein-Barr virus in chronic active infection and haematological malignancy. Nat Microbiol. 2019;4:404–13. https://doi.org/10.1038/s41564-018-0334-0.

    Article  CAS  PubMed  Google Scholar 

  10. Venturini C, Houldcroft CJ, Lazareva A, Wegner F, Morfopoulou S, Amrolia PJ, et al. Epstein-Barr virus (EBV) deletions as biomarkers of response to treatment of chronic active EBV. Br J Haematol. 2021;195:249–55. https://doi.org/10.1111/bjh.17790.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Kinzel M, Kalra A, Khanolkar RA, Williamson TS, Li N, Khan F, et al. Rituximab toxicity after preemptive or therapeutic administration for post-transplant lymphoproliferative disorder. Transpl Cell Ther. 2023;29:43.e1–43.e8. https://doi.org/10.1016/j.jtct.2022.10.013.

    Article  CAS  Google Scholar 

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Acknowledgements

We would like to thank Rhalp Jaylord Valenzuela for his statistical expertise.

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Authors and Affiliations

  1. Department of Hematology, Hokkaido University, Faculty of Medicine, Graduate School of Medicine, Sapporo, Japan

    Preeti Prerna M. Vaswani, Masahiro Onozawa, Yuta Hasegawa, Hiroyuki Ohigashi, Takahide Ara, Toshihiro Matsukawa, Atsushi Yasumoto, Souichi Shiratori, Hideki Goto, Masao Nakagawa, Kaoru Kahata, Tomoyuki Endo, Daigo Hashimoto & Takanori Teshima

  2. Section of Hematology, Division of Internal Medicine, National Kidney and Transplant Institute, Quezon City, Philippines

    Preeti Prerna M. Vaswani

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PPMV and MO designed the research, analyzed the data, and wrote the manuscript. All the authors contributed to data collection and review of the manuscript. All authors approved the final manuscript for publishing.

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Correspondence to Masahiro Onozawa.

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Vaswani, P.P.M., Onozawa, M., Hasegawa, Y. et al. Incidence and course of Epstein-Barr virus viremia after allogeneic hematopoietic stem cell transplant for adult-onset systemic chronic active Epstein-Barr virus disease. Bone Marrow Transplant 58, 1397–1399 (2023). https://doi.org/10.1038/s41409-023-02103-3

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