Prognostic impact of EBV serostatus in patients with lymphomas or chronic malignancies undergoing allogeneic HCT


The influence of the donor (D) and recipient (R) pre-transplant Epstein-Barr Virus (EBV) serostatus on transplant outcomes (overall survival, relapse-free survival, relapse incidence, non-relapse mortality, acute and chronic GVHD) in 12,931 patients with lymphomas or chronic malignancies undergoing allogeneic hematopoietic cell transplant (allo-HCT) between 1997–2016 was analyzed. In multivariate analysis, the risk of development of chronic GVHD was increased for EBV R+/D+ (HR = 1.26; p = 0.003), R+/D− (HR = 1.21; p = 0.044), and R−/D + (HR = 1.21; p = 0.048) in comparison to R−/D− transplants. No significance was shown for other transplant outcomes; however, in univariate analysis, EBV-seropositive patients receiving grafts from EBV-seropositive donors (EBV R+/D+transplants) had inferior transplant outcomes in comparison to EBV-seronegative recipients of grafts from EBV-seronegative donors (EBV R−/D−): inferior overall survival (59.6% vs 65.9%), inferior relapse-free survival (51.1% vs 57.5%), increased incidence of chronic GVHD (49.5% vs 41.8%), and increased incidence of de novo chronic GVHD (30.5% vs 24.0%). In conclusion, an EBV-negative recipient with lymphoma or chronic malignancy can benefit from selection of an EBV-negative donor in context of chronic GVHD, while there are no preferences in donor EBV serostatus for EBV-seropositive recipient.

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  1. 1.

    Styczynski J, Tridello G, Gil L, Ljungman P, Hoek J, Iacobelli S, et al. Impact of donor epstein-barr virus serostatus on the incidence of graft-versus-host disease in patients with acute leukemia after hematopoietic stem-cell transplantation: a study from the acute leukemia and infectious diseases working parties of the European Society for Blood and Marrow Transplantation. J Clin Oncol. 2016;34:2212–20.

  2. 2.

    Styczynski J, Reusser P, Einsele H, de la Camara R, Cordonnier C, Ward KN, et al. Management of HSV, VZV and EBV infections in patients with hematological malignancies and after SCT: guidelines from the Second European Conference on Infections in Leukemia. Bone Marrow Transpl. 2009;43:757–70.

  3. 3.

    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;91:1059–67.

  4. 4.

    Curtis RE, Travis LB, Rowlings PA, Socie G, Kingma DW, Banks PM, et al. Risk of lymphoproliferative disorders after bone marrow transplantation: a multi-institutional study. Blood. 1999;94:2208–16.

  5. 5.

    Styczynski J, Gil L, Tridello G, Ljungman P, Donnelly JP, van der Velden W, et al. Response to rituximab-based therapy and risk factor analysis in Epstein Barr Virus-related lymphoproliferative disorder after hematopoietic stem cell transplant in children and adults: a study from the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation. Clin Infect Dis. 2013;57:794–802.

  6. 6.

    Glucksberg H, Storb R, Fefer A, Buckner CD, Neiman PE, Clift RA, et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation. 1974;18:295–304.

  7. 7.

    Iacobelli S. Suggestions on the use of statistical methodologies in studies of the European Group for Blood and Marrow Transplantation. Bone Marrow Transpl. 2013;48(Suppl 1):S1–37.

  8. 8.

    Klein JP, Moeschberger ML. Survival analysis: techniques for censored and truncated data. New York: Springer-Verlag; 2003.

  9. 9.

    Zhang MJ, Fine J. Summarizing differences in cumulative incidence functions. Stat Med. 2008;27:4939–49.

  10. 10.

    Schemper M, Smith TL. A note on quantifying follow-up in studies of failure time. Control Clin Trials. 1996;17:343–6.

  11. 11.

    Zeiser R, Blazar BR. Pathophysiology of chronic graft-versus-host disease and therapeutic targets. N Engl J Med. 2017;377:2565–79.

  12. 12.

    Olivieri J, Manfredi L, Postacchini L, Tedesco S, Leoni P, Gabrielli A, et al. Consensus recommendations for improvement of unmet clinical needs—the example of chronic graft-versus-host disease: a systematic review and meta-analysis. Lancet Haematol. 2015;2:297–305.

  13. 13.

    Malard F, Labopin M, Yakoub-Agha I, Chantepie S, Guillaume T, Blaise D, et al. Rituximab-based first-line treatment of cGVHD after allogeneic SCT: results of a phase 2 study. Blood. 2017;v130:2186–95.

  14. 14.

    Dai YM, Liu HY, Liu YF, Zhang Y, He W. EBV transformation induces overexpression of hMSH2/3/6 on B lymphocytes and enhances gammadeltaT-cell-mediated cytotoxicity via TCR and NKG2D. Immunology. 2018.

  15. 15.

    Morishima S, Nakamura S, Yamamoto K, Miyauchi H, Kagami Y, Kinoshita T, et al. Increased T-cell responses to Epstein-Barr virus with high viral load in patients with Epstein-Barr virus-positive diffuse large B-cell lymphoma. Leuk Lymphoma. 2015;56:1072–8.

  16. 16.

    Cohen JI. Epstein-Barr virus infection. N Engl J Med. 2000;343:481–92.

  17. 17.

    Rezvani K, Champlin RE. Epstein-Barr virus and B cells in the pathogenesis of graft-versus-host disease after allogeneic hematopoietic stem-cell transplantation. J Clin Oncol. 2016;34:2201–2.

  18. 18.

    de Masson A, Bouaziz JD, Le Buanec H, Robin M, O’Meara A, Parquet N, et al. CD24(hi)CD27(+) and plasmablast-like regulatory B cells in human chronic graft-versus-host disease. Blood. 2015;125:1830–9.

  19. 19.

    Khoder A, Sarvaria A, Alsuliman A, Chew C, Sekine T, Cooper N, et al. Regulatory B cells are enriched within the IgM memory and transitional subsets in healthy donors but are deficient in chronic GVHD. Blood. 2014;124:2034–45.

  20. 20.

    Forcade E, Kim HT, Cutler C, Wang K, Alho AC, Nikiforow S, et al. Circulating T follicular helper cells with increased function during chronic graft-versus-host disease. Blood. 2016;127:2489–97.

  21. 21.

    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.

  22. 22.

    Styczyński J, Czyżewski K, Frączkiewicz J, Salamonowicz M, Zając-Spychała O, Zaucha-Prażmo A, et al. Viral infections in children undergoing hematopoietic stem cell transplantation: report 2016 of Polish Pediatric Infectious Working Group of Polish Society of Pediatric Oncology and Hematology. Acta Haematol Pol. 2017;48:23–7.

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The authors thank all EBMT transplant centers for reporting data to the EBMT Registry.

Author information

Study design: JS, LG and SC; Data analysis and interpretation: JS, GT, LG, NKn, MMik and PL; Manuscript writing: JS, GT, LG and KNW; Provision of important clinical data: JS, LG, PL, CC, RdlC, DA, GS, PC, DB, IYA, EF, JC, JM, EP, SNQ, HV, NS, JP, MMic, NF, ED, NR, GB, PB, SM, NKr and SC; Microbiology check-up: KNW; Data check-up: NKn and GT; Statistical analysis: GT; Administrative support: JS, NKn and SC; Revision of manuscript: All authors; Final approval: All authors.

Correspondence to Jan Styczynski.

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The authors declare that they have no conflict of interest.

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Results of this study were presented at 59th Annual Meeting of American Society of Hematology, Atlanta, December 9–12, 2017

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Styczynski, J., Tridello, G., Gil, L. et al. Prognostic impact of EBV serostatus in patients with lymphomas or chronic malignancies undergoing allogeneic HCT. Bone Marrow Transplant 54, 2060–2071 (2019) doi:10.1038/s41409-019-0627-9

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