Skip to main content

Advertisement

Log in

Dynamic changes in circulating EBV-DNA load during treatment have prognostic values in EBV+ DLBCL-NOS: a Chinese cohort study

  • Original Article
  • Published:
Annals of Hematology Aims and scope Submit manuscript

Abstract

EBV-positive diffuse large B-cell lymphoma, not otherwise specified (EBV+ DLBCL-NOS), is an EBV-positive clonal B-cell lymphoid proliferation and circulating EBV-DNA is a great indicator for prognosis among EBV associated disease. In this retrospective study, we report 66 EBV+ DLBCL cases among 2137 DLBCL-NOS cases diagnosed from 2013 to 2021 (prevalence of 6.0%). After a median follow-up of 27 months, progression-free survival (PFS) and overall survival (OS) at 2 years were 39.5% ± 6.2% and 53.6% ± 6.4%, respectively. Multivariate analysis showed that only the biomarker of the positivity of post treatment EBV-DNA had a borderline correlation with shorter PFS and OS (PFS: P = 0.053; OS: P = 0.065). Patients were divided into three subgroups according to dynamic changes of EBV-DNA status: EBV-DNA persistently negative group, EBV-DNA persistently positive group, and EBV-DNA transformed from positive to negative group; among the three groups, patients of the persistently positive group had worst PFS and OS (P = 0.0527 and P = 0.0139, respectively). Decline in EBV copies correlated significantly with treatment response as well. In conclusion, circulating EBV-DNA level played a vital role in prognostic and monitoring marker for EBV+ DLBCL-NOS.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

Data availability

The data generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

References

  1. Liang JH, Lu TX, Tian T, Wang L, Fan L, Xu J et al (2015) Epstein-Barr virus (EBV) DNA in whole blood as a superior prognostic and monitoring factor than EBV-encoded small RNA in situ hybridization in diffuse large B-cell lymphoma. Clin Microbiol Infect 21(6):596–602

    Article  CAS  PubMed  Google Scholar 

  2. Lu TX, Liang JH, Miao Y, Fan L, Wang L, Qu XY et al (2015) Epstein-Barr virus positive diffuse large B-cell lymphoma predict poor outcome, regardless of the age. Sci Rep 5:12168

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Beltran BE, Morales D, Quiñones P, Medeiros LJ, Miranda RN, Castillo JJ (2011) EBV-positive diffuse large b-cell lymphoma in young immunocompetent individuals. Clin Lymphoma Myeloma Leuk 11(6):512–516

    Article  PubMed  Google Scholar 

  4. Cohen M, Narbaitz M, Metrebian F, De Matteo E, Preciado MV, Chabay PA (2014) Epstein-Barr virus-positive diffuse large B-cell lymphoma association is not only restricted to elderly patients. Int J Cancer 135(12):2816–2824

    Article  CAS  PubMed  Google Scholar 

  5. Hong JY, Yoon DH, Suh C, Huh J, Do IG, Sohn I et al (2015) EBV-positive diffuse large B-cell lymphoma in young adults: is this a distinct disease entity? Ann Oncol 26(3):548–555

    Article  CAS  PubMed  Google Scholar 

  6. Nicolae A, Pittaluga S, Abdullah S, Steinberg SM, Pham TA, Davies-Hill T et al (2015) EBV-positive large B-cell lymphomas in young patients: a nodal lymphoma with evidence for a tolerogenic immune environment. Blood 126(7):863–872

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Shimoyama Y, Yamamoto K, Asano N, Oyama T, Kinoshita T, Nakamura S (2008) Age-related Epstein-Barr virus-associated B-cell lymphoproliferative disorders: special references to lymphomas surrounding this newly recognized clinicopathologic disease. Cancer Sci 99(6):1085–1091

    Article  CAS  PubMed  Google Scholar 

  8. Liang JH, Wang L, Peter Gale R, Wu W, Xia Y, Fan L et al (2017) Efficacy of pegaspargase, etoposide, methotrexate and dexamethasone in newly diagnosed advanced-stage extra-nodal natural killer/T-cell lymphoma with the analysis of the prognosis of whole blood EBV-DNA. Blood Cancer J 7(9):e608

    Article  PubMed  PubMed Central  Google Scholar 

  9. Liang JH, Lu L, Zhu HY, Li W, Fan L, Li JY et al (2019) The Prognostic Role of Circulating Epstein-Barr Virus DNA Copy Number in Angioimmunoblastic T-Cell Lymphoma Treated with Dose-Adjusted EPOCH. Cancer Res Treat 51(1):150–157

    Article  CAS  PubMed  Google Scholar 

  10. Qin JQ, Yin H, Wu JZ, Chen RZ, Xia Y, Wang L et al (2021) Pretreatment whole blood Epstein-Barr virus DNA predicts prognosis in Hodgkin lymphoma. Leuk Res 107:106607

    Article  CAS  PubMed  Google Scholar 

  11. Liang JH, Gao R, Xia Y, Gale RP, Chen RZ, Yang YQ et al (2016) Prognostic impact of Epstein-Barr virus (EBV)-DNA copy number at diagnosis in chronic lymphocytic leukemia. Oncotarget 7(2):2135–2142

    Article  PubMed  Google Scholar 

  12. Zhou XH, Liang JH, Wang L, Zhu HY, Wu JZ, Xia Y et al (2020) High viral loads of circulating Epstein-Barr virus DNA copy number in peripheral blood is associated with inferior prognosis in patients with mantle cell lymphoma. J Cancer 11(17):4980–4988

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Chen Y, Zheng X, Chen B, Yang X, Zheng J, Zheng Z et al (2017) The clinical significance of Epstein-Barr virus DNA in peripheral blood mononuclear cells in patients with non-Hodgkin lymphoma. Leuk Lymphoma 58(10):2349–2355

    Article  CAS  PubMed  Google Scholar 

  14. Zhou J, Huang J, Xiao M, Wang Y, Zhang W, Wan J et al (2022) Epstein-Barr virus copy number in peripheral blood mononuclear cells predicts prognosis in diffuse large B cell lymphoma. Leuk Lymphoma 63(7):1589–1597

    Article  CAS  PubMed  Google Scholar 

  15. Okamoto A, Yanada M, Inaguma Y, Tokuda M, Morishima S, Kanie T et al (2017) The prognostic significance of EBV DNA load and EBER status in diagnostic specimens from diffuse large B-cell lymphoma patients. Hematol Oncol 35(1):87–93

    Article  CAS  PubMed  Google Scholar 

  16. Cruz PM, Mo H, McConathy WJ, Sabnis N, Lacko AG (2013) The role of cholesterol metabolism and cholesterol transport in carcinogenesis: a review of scientific findings, relevant to future cancer therapeutics. Front Pharmacol 4:119

    Article  PubMed  PubMed Central  Google Scholar 

  17. Wang LW, Wang Z, Ersing I, Nobre L, Guo R, Jiang S et al (2019) Epstein-Barr virus subverts mevalonate and fatty acid pathways to promote infected B-cell proliferation and survival. PLoS Pathog 15(9):e1008030

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Gao R, Liang JH, Wang L, Zhu HY, Wu W, Cao L et al (2018) Low serum cholesterol levels predict inferior prognosis and improve NCCN-IPI scoring in diffuse large B cell lymphoma. Int J Cancer 143(8):1884–1895

    Article  CAS  PubMed  Google Scholar 

  19. Witte HM, Merz H, Biersack H, Bernard V, Riecke A, Gebauer J et al (2020) Impact of treatment variability and clinicopathological characteristics on survival in patients with Epstein-Barr-Virus positive diffuse large B cell lymphoma. Br J Haematol 189(2):257–268

    Article  CAS  PubMed  Google Scholar 

  20. Pan Y, Meng B, Zhang H, Cao W, Wang H, Bi C et al (2013) Low incidence of Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly in Tianjin, northern China. Leuk Lymphoma 54(2):298–303

    Article  CAS  PubMed  Google Scholar 

  21. Ahn JS, Yang DH, Duk Choi Y, Jung SH, Yhim HY, Kwak JY et al (2013) Clinical outcome of elderly patients with Epstein-Barr virus positive diffuse large B-cell lymphoma treated with a combination of rituximab and CHOP chemotherapy. Am J Hematol 88(9):774–779

    Article  CAS  PubMed  Google Scholar 

  22. Beltran BE, Castillo JJ, Morales D, de Mendoza FH, Quinones P, Miranda RN et al (2011) EBV-positive diffuse large B-cell lymphoma of the elderly: a case series from Peru. Am J Hematol 86(8):663–667

    Article  PubMed  Google Scholar 

  23. Slack GW, Steidl C, Sehn LH, Gascoyne RD (2014) CD30 expression in de novo diffuse large B-cell lymphoma: a population-based study from British Columbia. Br J Haematol 167(5):608–617

    Article  CAS  PubMed  Google Scholar 

  24. Bourbon E, Maucort-Boulch D, Fontaine J, Mauduit C, Sesques P, Safar V et al (2021) Clinicopathological features and survival in EBV-positive diffuse large B-cell lymphoma not otherwise specified. Blood Adv 5(16):3227–3239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R et al (2016) The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 127(20):2375–2390

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Oyama T, Yamamoto K, Asano N, Oshiro A, Suzuki R, Kagami Y et al (2007) Age-related EBV-associated B-cell lymphoproliferative disorders constitute a distinct clinicopathologic group: a study of 96 patients. Clin Cancer Res 13(17):5124–5132

    Article  CAS  PubMed  Google Scholar 

  27. Meriranta L, Alkodsi A, Pasanen A, Lepistö M, Mapar P, Blaker YN et al (2022) Molecular features encoded in the ctDNA reveal heterogeneity and predict outcome in high-risk aggressive B-cell lymphoma. Blood 139(12):1863–1877

    Article  CAS  PubMed  Google Scholar 

  28. Elgui de Oliveira D, Müller-Coan BG, Pagano JS (2016) Viral carcinogenesis beyond malignant transformation: EBV in the progression of human cancers. Trends Microbiol 24(8):649–64

    Article  CAS  PubMed  Google Scholar 

  29. Malpica L, Marques-Piubelli ML, Beltran BE, Chavez JC, Miranda RN, Castillo JJ (2022) EBV-positive diffuse large B-cell lymphoma, not otherwise specified: 2022 update on diagnosis, risk-stratification, and management. Am J Hematol 97(7):951–965

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This study was supported by the National Natural Science Foundation of China (grants 81770166, 81700193, 82170186, and 81720108002), Jiangsu Province’s Medical Elite Programme (ZDRCA2016022), Project of the National Key Clinical Specialty, the Jiangsu Provincial Special Program of Medical Science (BE2017751), the National Science and Technology Major Project (2018ZX09734007), the China Postdoctoral Science Foundation (2021M691336), and the Jiangsu Postdoctoral Science Foundation (2021K083A).

Author information

Authors and Affiliations

Authors

Contributions

Tong-Yao Xing, Zi-Wen Duan, Jia-Zhu Wu, Yue Li and Li Wang: Conceptualization, methodology, data curation, formal analysis, writing-original draft, and visualization.

Wei-Ting Wang, Kai-Xin Du, Hao-Rui Shen and Hua Yin: Data curation, formal analysis, and visualization. Tong-Yao Xing, Zi-Wen Duan and Jin-Hua Liang: Conceptualization, writing-review & editing, and supervision. Wei Xu and Jian-Yong Li: Conceptualization, methodology, funding acquisition, supervision, writing-review & editing.

Corresponding authors

Correspondence to Jin-Hua Liang or Wei Xu.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Tong-Yao Xing, Zi-Wen Duan, Wei-Ting Wang, Kai-Xin Du, Hao-Rui Shen, Hua Yin, Jia-Zhu Wu, Yue Li, Li Wang, Jia-Yong Li, Jin-Hua Liang, Wei Xu.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 242 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xing, TY., Duan, ZW., Wang, WT. et al. Dynamic changes in circulating EBV-DNA load during treatment have prognostic values in EBV+ DLBCL-NOS: a Chinese cohort study. Ann Hematol 102, 2471–2481 (2023). https://doi.org/10.1007/s00277-023-05260-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-023-05260-z

Keywords

Navigation