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Epstein-Barr virus central nervous system involvement in Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis

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Abstract

Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is a common subtype of secondary HLH. EBV plays an important part in the course. EBV can cause central nervous system (CNS) infections, and there are few clinical studies on EBV-CNS infection in EBV-HLH patients. All patients who were diagnosed as EBV-HLH and underwent cerebrospinal fluid testing admitted to our center from January 2018 to December 2019 were retrospectively analyzed. Summarized the clinical data, evaluated treatment efficacy after intrathecal injection, and investigated the correlation between EBV-CNS infection with prognosis in EBV-HLH patients. Of 37 of 57 (64.9%) EBV-HLH patients has EBV-CNS infection. The survival of EBV-HLH patients without EBV-CNS infection was significantly better than that in EBV-CNS infection patients (P = 0.018). There were no statistically significant differences in sCD25, ferritin, ALT, AST, LDH, TB, WBC, Hb, and PLT counts between two groups (all P-values > 0.05). Higher EBV-DNA load in peripheral blood was correlated with EBV-CNS infection (P < 0.001). EBV-CNS infection is an independent risk factor affecting the survival of patients (P = 0.004). The CSF cell load of patients with and without EBV-CNS infection groups was significantly different (P = 0.024). Intrathecal injection with methotrexate combined with dexamethasone can effectively decrease CSF EBV-DNA load (P = 0.017) and CSF cell load (P = 0.025). EBV-CNS infection is an independent risk factor affecting prognosis in EBV-HLH patients. Therefore, EBV-CNS infection should cause concern for EBV-HLH patients. Cerebrospinal fluid testing is necessary for all patients. Methotrexate combined with dexamethasone intrathecal injection can be an effective treatment for EBV-CNS infection.

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Data availability

The datasets used during the current study are available from the corresponding author on request.

Materials availability

The datasets used during the current study are available from the corresponding author on request.

References

  1. Ishii E, Ohga S, Imashuku S, Yasukawa M, Tsuda H, Miura I et al (2007) Nationwide survey of hemophagocytic lymphohistiocytosis in Japan. Int J Hematol 86:58–65. https://doi.org/10.1532/IJH97.07012

    Article  PubMed  Google Scholar 

  2. Imashuku S (2002) Clinical features and treatment strategies of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis. Crit Rev Oncol Hematol 44(3):259–272. https://doi.org/10.1016/s1040-8428(02)00117-8

    Article  PubMed  Google Scholar 

  3. Zeng X, Wei N, Wang Y, Wang J, Zhang J, Wu L, Huang W, Gao Z, Pei R, Chen J, Jin Z, Wang Z (2015) Treatment outcomes and prognostic analysis of 61 Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis. Zhonghua Xue Ye Xue Za Zhi 36(6):507–510. https://doi.org/10.3760/cma.j.issn.0253-2727.2015.06.013

    Article  CAS  PubMed  Google Scholar 

  4. Janka G (2009) Hemophagocytic lymphohistiocytosis: when the immune system runs amok. Klin Padiatr 221(5):278–285. https://doi.org/10.1055/s-0029-1237386

    Article  CAS  PubMed  Google Scholar 

  5. Yamashita N, Kimura H, Morishima T (2005) Virological aspects of Epstein-Barr virus infections. Acta Med Okayama 59(6):239–246. https://doi.org/10.18926/AMO/31961

    Article  CAS  PubMed  Google Scholar 

  6. Bharucha T, Houlihan CF, Breuer J (2019) Herpesvirus infections of the central nervous system. Semin Neurol 39(3):369–382. https://doi.org/10.1055/s-0039-1687837

    Article  PubMed  Google Scholar 

  7. Fujimoto H, Asaoka K, Imaizumi T, Ayabe M, Shoji H, Kaji M (2003) Epstein-Barr virus infections of the central nervous system. Int Med (Tokyo, Japan) 42(1):33–40. https://doi.org/10.2169/internalmedicine.42.33

    Article  Google Scholar 

  8. Kato I, Nishinaka-Arai Y, Nakamura M, Akarca AU, Niwa A, Ozawa H, …, Ueno H (2016) VEGFA- a new therapeutic target in CNS leukemia. Blood 128(22):911–911

  9. Boehme V, Schmitz N, Zeynalova S, Loeffler M, Pfreundschuh M (2009) CNS events in elderly patients with aggressive lymphoma treated with modern chemotherapy (CHOP-14) with or without rituximab: an analysis of patients treated in the RICOVER-60 trial of the German high-grade non-Hodgkin lymphoma study group (DSHNHL). Blood 113(17):3896–3902

    Article  CAS  Google Scholar 

  10. Henter J-I, Horne A, Aricó M, Egeler RM, Filipovich AH, Imashuku S, …, Winiarski J (2007) HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatric Blood Cancer 48(2):124–131

  11. Fryer JF, Heath AB, Wilkinson DE, Minor PD, Collaborative Study G (2016) A collaborative study to establish the 1st WHO International Standard for Epstein-Barr virus for nucleic acid amplification techniques. Biologicals 44:423–33

    Article  CAS  Google Scholar 

  12. Wang J, Wang Y, Wu L, Zhang J, Lai W, Wang Z (2016) PEG-aspargase and DEP regimen combination therapy for refractory Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis. J Hematol Oncol 9(1):84. https://doi.org/10.1186/s13045-016-0317-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank the patients and their families for participating in our study.

Funding

This work was supported by the National Natural Science Foundation of China (no. 81871633); Beijing Natural Science Foundation (no. 7181003); Beijing Municipal Administration of Hospitals’ Ascent Plan (DFL20180101).

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Authors and Affiliations

  1. Department of Hematology, Beijing Friendship Hospital, Capital Medical University, YongAn Road 95th Xicheng District, Beijing, China

    Qingxia Yin, Jingshi Wang & Zhao Wang

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  1. Qingxia Yin
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  2. Jingshi Wang
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  3. Zhao Wang
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Correspondence to Zhao Wang.

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The study was approved by the Ethics Committee at Beijing Friendship Hospital.

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Yin, Q., Wang, J. & Wang, Z. Epstein-Barr virus central nervous system involvement in Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis. Ann Hematol 101, 2471–2476 (2022). https://doi.org/10.1007/s00277-022-04957-x

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