Prevalence, management, and new treatment modalities of EBV-DNA-emia and EBV-PTLD after allo-HCT: survey of Infectious Diseases Working Party EBMT.


Journal

Bone marrow transplantation
ISSN: 1476-5365
Titre abrégé: Bone Marrow Transplant
Pays: England
ID NLM: 8702459

Informations de publication

Date de publication:
23 Oct 2023
Historique:
received: 02 07 2023
accepted: 13 10 2023
revised: 28 09 2023
medline: 24 10 2023
pubmed: 24 10 2023
entrez: 23 10 2023
Statut: aheadofprint

Résumé

The aim of this study was to determine the current approach of EBV-driven post-transplant complications in context of monitoring, diagnosis, prevalence and treatment in EBMT transplant centers. Routine serology testing in patient and donor before HCT is performed in 95.5% centers. Pretransplant EBV-DNA is routinely tested in all patients in 32.7% centers. Monitoring for EBV infection is feasible in 98.2% centers: including 66.7% centers using standardized PCR. Post-HCT regular monitoring is performed in all patients in 80.5% centers. Anti-EBV prophylaxis with rituximab is used in 12.4% centers. Frequency of csEBV-DNA-emia was 7.4% (adults: 6.2%, children: 12.6%). The PCR threshold used to start preemptive treatment was differentiated among centers. Frequency of EBV-PTLD was 1.6% (adults: 1.3%; children: 3.5%). First-line therapy of EBV-driven complications was rituximab and reduction of immunosuppressive therapy. The rate of failure of first-line preemptive treatment was 12.0%. EBV-specific viral-specific T-lymphocytes were available in 46.0% centers. A number of new experimental therapies were given in 28 patients with resistant/refractory PTLD. In conclusion, the prevalence of EBV-DNA-emia and EBV-PTLD over the period 2020-2021 decreased in comparison to historical data. New trends (routine pretransplant screening for EBV-DNA, wider access to VST, new experimental therapies) are being observed in management of EBV infection after allo-HCT.

Identifiants

pubmed: 37872300
doi: 10.1038/s41409-023-02129-7
pii: 10.1038/s41409-023-02129-7
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2023. The Author(s), under exclusive licence to Springer Nature Limited.

Références

Styczynski J. Managing post-transplant lymphoproliferative disorder. Expert Opinion on Orphan Drugs. 2017;5:19–35.
doi: 10.1080/21678707.2017.1262256
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.
doi: 10.1200/JCO.2015.64.2405 pubmed: 27091716
Styczynski J, Tridello G, Gil L, Ljungman P, Mikulska M, Ward KN, et al. Prognostic impact of EBV serostatus in patients with lymphomas or chronic malignancies undergoing allogeneic HCT. Bone Marrow Transplant. 2019;54:2060–71.
doi: 10.1038/s41409-019-0627-9 pubmed: 31363166
Styczynski J, Tridello G, Gil L, Ljungman P, Mikulska M, van der Werf S, et al. Prognostic impact of Epstein–Barr virus serostatus in patients with nonmalignant hematological disorders undergoing allogeneic hematopoietic cell transplantation: the study of Infectious Diseases Working Party of the European Society for Blood and Marrow Transplantation. Acta Haematol Pol. 2020;51:73–80.
doi: 10.2478/ahp-2020-0015
Galazka P, Szafranska M, Jaremek K, Rutkowska D, Czyzewski K, Debski R, et al. Long-term follow-up of pediatric patients with EBV-related post-transplant lymphoproliferative disorder. Acta Haematol Pol. 2021;52:597–600.
doi: 10.5603/AHP.a2021.0099
Kolodziejczak M, Gil L, de la Camara R, Styczynski J. Impact of donor and recipient Epstein-Barr Virus serostatus on outcomes of allogeneic hematopoietic cell transplantation: a systematic review and meta-analysis. Ann Hematol. 2021;100:763–77.
doi: 10.1007/s00277-021-04428-9 pubmed: 33491135 pmcid: 7914248
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.
doi: 10.3324/haematol.2016.144428 pubmed: 27365460 pmcid: 5004459
Marjanska A, Styczynski J. Who is the patient at risk for EBV reactivation and disease: expert opinion focused on post-transplant lymphoproliferative disorders following hematopoietic stem cell transplantation. Expert Opin Biol Ther. 2023;23:539–52.
doi: 10.1080/14712598.2023.2196366 pubmed: 36971380
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 Transplant. 2009;43:757–70.
doi: 10.1038/bmt.2008.386 pubmed: 19043458
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.
doi: 10.1093/cid/cit391 pubmed: 23771985
Williams-Aziz SL, Hartline CB, Harden EA, Daily SL, Prichard MN, Kushner NL, et al. Comparative activities of lipid esters of cidofovir and cyclic cidofovir against replication of herpesviruses in vitro. Antimicrob Agents Chemother. 2005;49:3724–33.
doi: 10.1128/AAC.49.9.3724-3733.2005 pubmed: 16127046 pmcid: 1195409
Wang FZ, Roy D, Gershburg E, Whitehurst CB, Dittmer DP, Pagano JS. Maribavir inhibits Epstein-Barr virus transcription in addition to viral DNA replication. J Virol. 2009;83:12108–17.
doi: 10.1128/JVI.01575-09 pubmed: 19759127 pmcid: 2786727
Whitehurst CB, Sanders MK, Law M, Wang FZ, Xiong J, Dittmer DP, et al. Maribavir inhibits Epstein-Barr virus transcription through the EBV protein kinase. J Virol. 2013;87:5311–5.
doi: 10.1128/JVI.03505-12 pubmed: 23449792 pmcid: 3624302
Camargo JF, Morris MI, Abbo LM, Simkins J, Saneeymehri S, Alencar MC, et al. The use of brincidofovir for the treatment of mixed dsDNA viral infection. J Clin Virol. 2016;83:1–4.
doi: 10.1016/j.jcv.2016.07.021 pubmed: 27513204
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. Transplant Cell Ther. 2023;29:43.e1–43.e8.
doi: 10.1016/j.jtct.2022.10.013 pubmed: 36273783

Auteurs

Jan Styczynski (J)

Department of Pediatric Hematology and Oncology, Collegium Medicum Nicolaus Copernicus University Torun, Bydgoszcz, Poland. jstyczynski@cm.umk.pl.

Gloria Tridello (G)

EBMT, Leiden Study Unit, Leiden, The Netherlands.

Lotus Wendel (L)

EBMT, Leiden Study Unit, Leiden, The Netherlands.

Nina Knelange (N)

EBMT, Leiden Study Unit, Leiden, The Netherlands.

Simone Cesaro (S)

Pediatric Hematology Oncology, Department of the Mother and Child, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.

Lidia Gil (L)

University of Medical Sciences, Poznan, Poland.

Per Ljungman (P)

Karolinska University Hospital, Karolinska Comprehensive Cancer Center, and Karolinska Institutet, Stockholm, Sweden.

Malgorzata Mikulska (M)

Division of Infectious Diseases, University of Genoa and Ospedale Policlinico San Martino, Genova, Italy.

Dina Averbuch (D)

Faculty of Medicine, Hebrew University of Jerusalem, Hadassah Medical Center, Jerusalem, Israel.

Rafael de la Camara (R)

Hospital Universitario de la Princesa, Madrid, Spain.

Classifications MeSH