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Sintilimab treatment for chronic active Epstein–Barr virus infection and Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis in children

BACKGROUND: Chronic active Epstein–Barr virus infection (CAEBV) and Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) are rare but life-threatening progressive diseases triggered by EBV infection. Glucocorticoid/immunosuppressants treatment is temporarily effective; however,...

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Autores principales: Chen, Ruyue, Lin, Qiang, Zhu, Yun, Shen, Yunyan, Xu, Qinying, Tang, Hanyun, Cui, Ningxun, Jiang, Lu, Dai, Xiaomei, Chen, Weiqing, Li, Xiaozhong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10514962/
https://www.ncbi.nlm.nih.gov/pubmed/37736751
http://dx.doi.org/10.1186/s13023-023-02861-9
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author Chen, Ruyue
Lin, Qiang
Zhu, Yun
Shen, Yunyan
Xu, Qinying
Tang, Hanyun
Cui, Ningxun
Jiang, Lu
Dai, Xiaomei
Chen, Weiqing
Li, Xiaozhong
author_facet Chen, Ruyue
Lin, Qiang
Zhu, Yun
Shen, Yunyan
Xu, Qinying
Tang, Hanyun
Cui, Ningxun
Jiang, Lu
Dai, Xiaomei
Chen, Weiqing
Li, Xiaozhong
author_sort Chen, Ruyue
collection PubMed
description BACKGROUND: Chronic active Epstein–Barr virus infection (CAEBV) and Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) are rare but life-threatening progressive diseases triggered by EBV infection. Glucocorticoid/immunosuppressants treatment is temporarily effective; however, most patients relapse and/or progress. Hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy; however, there are risks of transplantation-associated complications. Currently there is no standard treatment for CAEBV and EBV-HLH. Programmed death protein 1 (PD-1) inhibitors have achieved a high response in many EBV-related diseases. Sintilimab (a recombinant human IgG4 monoclonal antibody against PD-1) disrupts the interaction between PD-1 and its ligand, leading to T cell reinvigoration. METHODS: A retrospective analysis was performed on three children with CAEBV or EBV-HLH in the Children’s Hospital of Soochow University between 12 December 2020 and 28 November 2022. The efficacy of sintilimab was evaluated. RESULTS: Three patients, including two males and one female, were analyzed. Among them, two children were diagnosed with CAEBV with intermittent fever for more than four years, and one child was diagnosed with EBV-HLH. After sintilimab treatment and a mean follow-up of 17.1 months (range 10.0–23.3 months), patients 1 and 3 achieved a complete clinical response and patient 2 achieved a partial clinical response. All three children showed a > 50% decrease in EBV-DNA load in both blood and plasma. EBV-DNA copies in sorted T, B, and NK cells were also markedly decreased after sintilimab treatment. CONCLUSION: Our data supported the efficacy of PD-1 targeted therapy in certain patients with CAEBV and EBV-HLH, and suggested that sintilimab could provide a cure for these diseases, without HSCT. More prospective studies and longer follow-up are needed to confirm these conclusions.
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spelling pubmed-105149622023-09-23 Sintilimab treatment for chronic active Epstein–Barr virus infection and Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis in children Chen, Ruyue Lin, Qiang Zhu, Yun Shen, Yunyan Xu, Qinying Tang, Hanyun Cui, Ningxun Jiang, Lu Dai, Xiaomei Chen, Weiqing Li, Xiaozhong Orphanet J Rare Dis Research BACKGROUND: Chronic active Epstein–Barr virus infection (CAEBV) and Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) are rare but life-threatening progressive diseases triggered by EBV infection. Glucocorticoid/immunosuppressants treatment is temporarily effective; however, most patients relapse and/or progress. Hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy; however, there are risks of transplantation-associated complications. Currently there is no standard treatment for CAEBV and EBV-HLH. Programmed death protein 1 (PD-1) inhibitors have achieved a high response in many EBV-related diseases. Sintilimab (a recombinant human IgG4 monoclonal antibody against PD-1) disrupts the interaction between PD-1 and its ligand, leading to T cell reinvigoration. METHODS: A retrospective analysis was performed on three children with CAEBV or EBV-HLH in the Children’s Hospital of Soochow University between 12 December 2020 and 28 November 2022. The efficacy of sintilimab was evaluated. RESULTS: Three patients, including two males and one female, were analyzed. Among them, two children were diagnosed with CAEBV with intermittent fever for more than four years, and one child was diagnosed with EBV-HLH. After sintilimab treatment and a mean follow-up of 17.1 months (range 10.0–23.3 months), patients 1 and 3 achieved a complete clinical response and patient 2 achieved a partial clinical response. All three children showed a > 50% decrease in EBV-DNA load in both blood and plasma. EBV-DNA copies in sorted T, B, and NK cells were also markedly decreased after sintilimab treatment. CONCLUSION: Our data supported the efficacy of PD-1 targeted therapy in certain patients with CAEBV and EBV-HLH, and suggested that sintilimab could provide a cure for these diseases, without HSCT. More prospective studies and longer follow-up are needed to confirm these conclusions. BioMed Central 2023-09-22 /pmc/articles/PMC10514962/ /pubmed/37736751 http://dx.doi.org/10.1186/s13023-023-02861-9 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Chen, Ruyue
Lin, Qiang
Zhu, Yun
Shen, Yunyan
Xu, Qinying
Tang, Hanyun
Cui, Ningxun
Jiang, Lu
Dai, Xiaomei
Chen, Weiqing
Li, Xiaozhong
Sintilimab treatment for chronic active Epstein–Barr virus infection and Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis in children
title Sintilimab treatment for chronic active Epstein–Barr virus infection and Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis in children
title_full Sintilimab treatment for chronic active Epstein–Barr virus infection and Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis in children
title_fullStr Sintilimab treatment for chronic active Epstein–Barr virus infection and Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis in children
title_full_unstemmed Sintilimab treatment for chronic active Epstein–Barr virus infection and Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis in children
title_short Sintilimab treatment for chronic active Epstein–Barr virus infection and Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis in children
title_sort sintilimab treatment for chronic active epstein–barr virus infection and epstein–barr virus-associated hemophagocytic lymphohistiocytosis in children
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10514962/
https://www.ncbi.nlm.nih.gov/pubmed/37736751
http://dx.doi.org/10.1186/s13023-023-02861-9
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