Skip to main content
Top
Published in: Annals of Hematology 3/2024

Open Access 29-12-2023 | Epstein-Barr Virus | Original Article

Clinical characteristics and outcomes of Epstein-Barr virus viral load after allogeneic hematopoietic stem cell transplantation

Authors: Takafumi Tsushima, Shin-Ichi Masuda, Natsumi Yoda, Sayaka Kainuma, Chiharu Kimeda, Shiho Konno, Kazusuke Tanaka, Kosuke Matsuo, Sonoko Shimoji, Kenji Kimura, Hironori Arai, Yoshikazu Utsu, Ken-Ichi Imadome, Nobuyuki Aotsuka

Published in: Annals of Hematology | Issue 3/2024

Login to get access

Abstract

Epstein-Barr virus (EBV) reactivation can occur following allogenic hematopoietic stem cell transplantation (allo-HSCT). However, the clinical characteristics and outcomes of EBV-viral load are not well known. Thus, we retrospectively analyzed the clinical features and prognostic impact of the EBV viral load in 121 allo-HSCT recipients from our hospital. EBV DNA quantification was performed in whole blood after transplantation. Patients were grouped based on whether EBV DNA quantification reached > 1000 copies/mL during follow-up (N = 50) or not (N = 71). Patients with EBV > 1000 EBV copies/mL were relatively more common in the groups with graft versus host disease (GVHD) prophylaxis including ATG, haploidentical donor type, peripheral blood as a donor source, and acute GVHD II–IV. The 20-month OS and DFS were not significantly different between patients with < 1000 EBV copies/mL and patients with > 1000 EBV copies/mL (20-month OS, 56.0% vs. 60.6%; p = 0.503, 20-month DFS, 50.0% vs. 57.7%; p = 0.179). Immunosuppressant (ISS) dose reduction was achieved after the maximum increase in EBV in 41/50 (82%) patients. Additionally, 30/50 (60%) patients achieved a 50% dose reduction or no restarting of ISS within 3 months of the maximum EBV increase. Among cases wherein EBV DNA quantification reached > 1000 copies/mL, those that achieved rapid dose reduction of ISS tended to have longer overall survival (“not reached” vs 5.4 months, p < 0.001) and disease-free survival (88.4 months vs 5.3 months, p < 0.001) than those in patients who did not. Our data highlight the importance of rapid ISS reduction in post-transplant EBV reactivation.
Appendix
Available only for authorised users
Literature
2.
go back to reference Curtis RE, Travis LB, Rowlings PA, Socié G, Kingma DW, Banks PM, Jaffe ES, Sale GE, Horowitz MM, Witherspoon RP, Shriner DA, Weisdorf DJ, Kolb HJ, Sullivan KM, Sobocinski KA, Gale RP, Hoover RN, Fraumeni JF Jr, Deeg HJ (1999) Risk of lymphoproliferative disorders after bone marrow transplantation: a multi-institutional study. Blood 94(7):2208–2216PubMed Curtis RE, Travis LB, Rowlings PA, Socié G, Kingma DW, Banks PM, Jaffe ES, Sale GE, Horowitz MM, Witherspoon RP, Shriner DA, Weisdorf DJ, Kolb HJ, Sullivan KM, Sobocinski KA, Gale RP, Hoover RN, Fraumeni JF Jr, Deeg HJ (1999) Risk of lymphoproliferative disorders after bone marrow transplantation: a multi-institutional study. Blood 94(7):2208–2216PubMed
4.
go back to reference Shapiro RS, McClain K, Frizzera G, Gajl-Peczalska KJ, Kersey JH, Blazar BR, Arthur DC, Patton DF, Greenberg JS, Burke B et al (1988) Epstein-Barr virus associated B cell lymphoproliferative disorders following bone marrow transplantation. Blood 71(5):1234–1243CrossRefPubMed Shapiro RS, McClain K, Frizzera G, Gajl-Peczalska KJ, Kersey JH, Blazar BR, Arthur DC, Patton DF, Greenberg JS, Burke B et al (1988) Epstein-Barr virus associated B cell lymphoproliferative disorders following bone marrow transplantation. Blood 71(5):1234–1243CrossRefPubMed
5.
go back to reference Zutter MM, Martin PJ, Sale GE, Shulman HM, Fisher L, Thomas ED, Durnam DM (1988) Epstein-Barr virus lymphoproliferation after bone marrow transplantation. Blood 72(2):520–529CrossRefPubMed Zutter MM, Martin PJ, Sale GE, Shulman HM, Fisher L, Thomas ED, Durnam DM (1988) Epstein-Barr virus lymphoproliferation after bone marrow transplantation. Blood 72(2):520–529CrossRefPubMed
6.
go back to reference Styczynski J, van der Velden W, Fox CP, Engelhard D, de la Camara R, Cordonnier C, Ljungman P (2016) 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 101(7):803–811. https://doi.org/10.3324/haematol.2016.144428CrossRefPubMedPubMedCentral Styczynski J, van der Velden W, Fox CP, Engelhard D, de la Camara R, Cordonnier C, Ljungman P (2016) 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 101(7):803–811. https://​doi.​org/​10.​3324/​haematol.​2016.​144428CrossRefPubMedPubMedCentral
7.
9.
go back to reference Deeg HJ, Storer BE, Boeckh M, Martin PJ, McCune JS, Myerson D, Heimfeld S, Flowers ME, Anasetti C, Doney KC, Hansen JA, Kiem HP, Nash RA, O’Donnell PV, Radich JP, Sandmaier BM, Scott BL, Sorror ML, Warren EH, Witherspoon RP, Woolfrey A, Appelbaum FR, Storb R (2006) Reduced incidence of acute and chronic graft-versus-host disease with the addition of thymoglobulin to a targeted busulfan/cyclophosphamide regimen. Biol Blood Marrow Transplant 12(5):573–584. https://doi.org/10.1016/j.bbmt.2005.12.036CrossRefPubMed Deeg HJ, Storer BE, Boeckh M, Martin PJ, McCune JS, Myerson D, Heimfeld S, Flowers ME, Anasetti C, Doney KC, Hansen JA, Kiem HP, Nash RA, O’Donnell PV, Radich JP, Sandmaier BM, Scott BL, Sorror ML, Warren EH, Witherspoon RP, Woolfrey A, Appelbaum FR, Storb R (2006) Reduced incidence of acute and chronic graft-versus-host disease with the addition of thymoglobulin to a targeted busulfan/cyclophosphamide regimen. Biol Blood Marrow Transplant 12(5):573–584. https://​doi.​org/​10.​1016/​j.​bbmt.​2005.​12.​036CrossRefPubMed
10.
go back to reference Carpenter B, Haque T, Dimopoulou M, Atkinson C, Roughton M, Grace S, Denovan S, Fielding A, Kottaridis PD, Griffiths P, Mackinnon S, Emery V, Chakraverty R (2010) Incidence and dynamics of Epstein-Barr virus reactivation after alemtuzumab-based conditioning for allogeneic hematopoietic stem-cell transplantation. Transplantation 90(5):564–570. https://doi.org/10.1097/TP.0b013e3181e7a3bfCrossRefPubMed Carpenter B, Haque T, Dimopoulou M, Atkinson C, Roughton M, Grace S, Denovan S, Fielding A, Kottaridis PD, Griffiths P, Mackinnon S, Emery V, Chakraverty R (2010) Incidence and dynamics of Epstein-Barr virus reactivation after alemtuzumab-based conditioning for allogeneic hematopoietic stem-cell transplantation. Transplantation 90(5):564–570. https://​doi.​org/​10.​1097/​TP.​0b013e3181e7a3bf​CrossRefPubMed
11.
12.
go back to reference Wang Y, Fu HX, Liu DH, Xu LP, Zhang XH, Chang YJ, Chen YH, Wang FR, Sun YQ, Tang FF, Liu KY, Huang XJ (2014) Influence of two different doses of antithymocyte globulin in patients with standard-risk disease following haploidentical transplantation: a randomized trial. Bone Marrow Transplant 49(3):426–433. https://doi.org/10.1038/bmt.2013.191CrossRefPubMed Wang Y, Fu HX, Liu DH, Xu LP, Zhang XH, Chang YJ, Chen YH, Wang FR, Sun YQ, Tang FF, Liu KY, Huang XJ (2014) Influence of two different doses of antithymocyte globulin in patients with standard-risk disease following haploidentical transplantation: a randomized trial. Bone Marrow Transplant 49(3):426–433. https://​doi.​org/​10.​1038/​bmt.​2013.​191CrossRefPubMed
16.
go back to reference Styczynski J, Gil L, Tridello G, Ljungman P, Donnelly JP, van der Velden W, Omar H, Martino R, Halkes C, Faraci M, Theunissen K, Kalwak K, Hubacek P, Sica S, Nozzoli C, Fagioli F, Matthes S, Diaz MA, Migliavacca M, Balduzzi A, Tomaszewska A, Camara Rde L, van Biezen A, Hoek J, Iacobelli S, Einsele H, Cesaro S (2013) 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 57(6):794–802. https://doi.org/10.1093/cid/cit391CrossRefPubMed Styczynski J, Gil L, Tridello G, Ljungman P, Donnelly JP, van der Velden W, Omar H, Martino R, Halkes C, Faraci M, Theunissen K, Kalwak K, Hubacek P, Sica S, Nozzoli C, Fagioli F, Matthes S, Diaz MA, Migliavacca M, Balduzzi A, Tomaszewska A, Camara Rde L, van Biezen A, Hoek J, Iacobelli S, Einsele H, Cesaro S (2013) 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 57(6):794–802. https://​doi.​org/​10.​1093/​cid/​cit391CrossRefPubMed
18.
go back to reference Muramatsu H, Takahashi Y, Shimoyama Y, Doisaki S, Nishio N, Ito Y, Hama A, Shimada A, Yagasaki H, Ito M, Kojima S (2011) CD20-negative Epstein-Barr virus-associated post-transplant lymphoproliferative disease refractory to rituximab in a patient with severe aplastic anemia. Int J Hematol 93(6):779–781. https://doi.org/10.1007/s12185-011-0870-3CrossRefPubMed Muramatsu H, Takahashi Y, Shimoyama Y, Doisaki S, Nishio N, Ito Y, Hama A, Shimada A, Yagasaki H, Ito M, Kojima S (2011) CD20-negative Epstein-Barr virus-associated post-transplant lymphoproliferative disease refractory to rituximab in a patient with severe aplastic anemia. Int J Hematol 93(6):779–781. https://​doi.​org/​10.​1007/​s12185-011-0870-3CrossRefPubMed
20.
go back to reference Bonney DK, Htwe EE, Turner A, Kelsey A, Shabani A, Hughes S, Hughes I, Wynn RF (2012) Sustained response to intrathecal rituximab in EBV associated post-transplant lymphoproliferative disease confined to the central nervous system following haematopoietic stem cell transplant. Pediatr Blood Cancer 58(3):459–461. https://doi.org/10.1002/pbc.23134CrossRefPubMed Bonney DK, Htwe EE, Turner A, Kelsey A, Shabani A, Hughes S, Hughes I, Wynn RF (2012) Sustained response to intrathecal rituximab in EBV associated post-transplant lymphoproliferative disease confined to the central nervous system following haematopoietic stem cell transplant. Pediatr Blood Cancer 58(3):459–461. https://​doi.​org/​10.​1002/​pbc.​23134CrossRefPubMed
21.
go back to reference Cesaro S, Pegoraro A, Tridello G, Calore E, Pillon M, Varotto S, Abate D, Barzon L, Mengoli C, Carli M, Messina C (2010) A prospective study on modulation of immunosuppression for Epstein-Barr virus reactivation in pediatric patients who underwent unrelated hematopoietic stem-cell transplantation. Transplantation 89(12):1533–1540. https://doi.org/10.1097/TP.0b013e3181dd6c0aCrossRefPubMed Cesaro S, Pegoraro A, Tridello G, Calore E, Pillon M, Varotto S, Abate D, Barzon L, Mengoli C, Carli M, Messina C (2010) A prospective study on modulation of immunosuppression for Epstein-Barr virus reactivation in pediatric patients who underwent unrelated hematopoietic stem-cell transplantation. Transplantation 89(12):1533–1540. https://​doi.​org/​10.​1097/​TP.​0b013e3181dd6c0a​CrossRefPubMed
24.
go back to reference van Esser JW, van der Holt B, Meijer E, Niesters HG, Trenschel R, Thijsen SF, van Loon AM, Frassoni F, Bacigalupo A, Schaefer UW, Osterhaus AD, Gratama JW, Löwenberg B, Verdonck LF, Cornelissen JJ (2001) Epstein-Barr virus (EBV) reactivation is a frequent event after allogeneic stem cell transplantation (SCT) and quantitatively predicts EBV-lymphoproliferative disease following T-cell–depleted SCT. Blood 98(4):972–978. https://doi.org/10.1182/blood.v98.4.972CrossRefPubMed van Esser JW, van der Holt B, Meijer E, Niesters HG, Trenschel R, Thijsen SF, van Loon AM, Frassoni F, Bacigalupo A, Schaefer UW, Osterhaus AD, Gratama JW, Löwenberg B, Verdonck LF, Cornelissen JJ (2001) Epstein-Barr virus (EBV) reactivation is a frequent event after allogeneic stem cell transplantation (SCT) and quantitatively predicts EBV-lymphoproliferative disease following T-cell–depleted SCT. Blood 98(4):972–978. https://​doi.​org/​10.​1182/​blood.​v98.​4.​972CrossRefPubMed
25.
go back to reference Fox CP, Burns D, Parker AN, Peggs KS, Harvey CM, Natarajan S, Marks DI, Jackson B, Chakupurakal G, Dennis M, Lim Z, Cook G, Carpenter B, Pettitt AR, Mathew S, Connelly-Smith L, Yin JA, Viskaduraki M, Chakraverty R, Orchard K, Shaw BE, Byrne JL, Brookes C, Craddock CF, Chaganti S (2014) EBV-associated post-transplant lymphoproliferative disorder following in vivo T-cell-depleted allogeneic transplantation: clinical features, viral load correlates and prognostic factors in the rituximab era. Bone Marrow Transplant 49(2):280–286. https://doi.org/10.1038/bmt.2013.170CrossRefPubMed Fox CP, Burns D, Parker AN, Peggs KS, Harvey CM, Natarajan S, Marks DI, Jackson B, Chakupurakal G, Dennis M, Lim Z, Cook G, Carpenter B, Pettitt AR, Mathew S, Connelly-Smith L, Yin JA, Viskaduraki M, Chakraverty R, Orchard K, Shaw BE, Byrne JL, Brookes C, Craddock CF, Chaganti S (2014) EBV-associated post-transplant lymphoproliferative disorder following in vivo T-cell-depleted allogeneic transplantation: clinical features, viral load correlates and prognostic factors in the rituximab era. Bone Marrow Transplant 49(2):280–286. https://​doi.​org/​10.​1038/​bmt.​2013.​170CrossRefPubMed
Metadata
Title
Clinical characteristics and outcomes of Epstein-Barr virus viral load after allogeneic hematopoietic stem cell transplantation
Authors
Takafumi Tsushima
Shin-Ichi Masuda
Natsumi Yoda
Sayaka Kainuma
Chiharu Kimeda
Shiho Konno
Kazusuke Tanaka
Kosuke Matsuo
Sonoko Shimoji
Kenji Kimura
Hironori Arai
Yoshikazu Utsu
Ken-Ichi Imadome
Nobuyuki Aotsuka
Publication date
29-12-2023
Publisher
Springer Berlin Heidelberg
Published in
Annals of Hematology / Issue 3/2024
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-023-05596-6

Other articles of this Issue 3/2024

Annals of Hematology 3/2024 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.