{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T18:52:49Z","timestamp":1793645569120,"version":"4.5.1"},"reference-count":12,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T00:00:00Z","timestamp":1747180800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T00:00:00Z","timestamp":1747180800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170206"],"award-info":[{"award-number":["82170206"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shanghai Municipal Health Commission Project of Disciplines of Excellence","award":["20234Z0002"],"award-info":[{"award-number":["20234Z0002"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Exp Hematol Oncol"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Letermovir is an antiviral agent that significantly decreases the frequency of cytomegalovirus (CMV) infections following allogeneic hematopoietic stem cell transplantation (allo-HCT); however, its impact on Epstein-Barr virus (EBV) infection remains unclear. This multicenter, retrospective study involved 565 patients aged\u2009\u2265\u200918\u00a0years, who underwent allo-HCT between January 2021 and December 2023, with 284 receiving letermovir prophylaxis (letermovir group) and 281 not (control group). Cumulative incidences of clinically significant CMV infection (cs-CMVi), EBV DNAemia, EBV-disease and post-transplant lymphoproliferative disorder (PTLD) were compared between the\u00a0groups. The 1-year cumulative incidence of EBV DNAemia did not differ significantly between the letermovir and control groups (58.1% <jats:italic>vs.<\/jats:italic> 52.7%,<jats:italic> P<\/jats:italic>\u2009=\u20090.3). However, letermovir prophylaxis was associated with a significantly higher incidence of PTLD within the first year post-HCT (7.39% vs. 1.80%, P\u2009=\u20090.00059). Multivariate analysis identified letermovir prophylaxis as an independent risk factor for PTLD (HR [95% CI]: 4.619 [1.458\u201310.278], P\u2009=\u20090.007). Letermovir altered the early reconstitution trajectory\u00a0after allo-HCT, particularly in CD8<jats:sup>+<\/jats:sup> T cells. Our findings emphasized that although letermovir prophylaxis did not increase the risk of EBV DNAemia in allo-HCT recipients, it was associated with a higher incidence of PTLD. Further studies focusing on immune reconstitutiom dynamics are warranted to elucidate the underlying pathophysiology of EBV-PTLD under letermovir pressure.<\/jats:p>","DOI":"10.1186\/s40164-025-00665-0","type":"journal-article","created":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T12:20:43Z","timestamp":1747225243000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Epstein-Barr virus infection following allogeneic hematopoietic stem cell transplantation in the era of letermovir for cytomegalovirus prophylaxis"],"prefix":"10.1186","volume":"14","author":[{"given":"Jingtao","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shixuan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruoxuan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zengkai","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luxiang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanhe","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayu","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zilu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanmin","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxia","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,14]]},"reference":[{"issue":"9","key":"665_CR1","doi-asserted-by":"publisher","first-page":"1754","DOI":"10.1038\/s41409-020-0831-7","volume":"55","author":"Y Ru","year":"2020","unstructured":"Ru Y, Zhang X, Song T, Ding Y, Zhu Z, Fan Y, et al. Epstein-Barr virus reactivation after allogeneic hematopoietic stem cell transplantation: multifactorial impact on transplant outcomes. Bone Marrow Transplant. 2020;55(9):1754\u201362.","journal-title":"Bone Marrow Transplant"},{"issue":"9","key":"665_CR2","doi-asserted-by":"publisher","first-page":"2163","DOI":"10.1007\/s00277-019-03742-7","volume":"98","author":"X-N Gao","year":"2019","unstructured":"Gao X-N, Lin J, Wang L-J, Li F, Li H-H, Wang S-H, et al. Risk factors and clinical outcomes of Epstein-Barr virus DNAemia and post-transplant lymphoproliferative disorders after haploidentical and matched-sibling PBSCT in patients with hematologic malignancies. Ann Hematol. 2019;98(9):2163\u201377.","journal-title":"Ann Hematol"},{"issue":"1","key":"665_CR3","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1007\/s10238-023-01270-3","volume":"24","author":"J Huang","year":"2024","unstructured":"Huang J, Pan Z, Wang L, Zhang Z, Huang J, Jiang C, et al. Early T-cell reconstitution predicts risk of EBV reactivation after allogeneic hematopoietic stem cell transplantation. Clin Exp Med. 2024;24(1):22.","journal-title":"Clin Exp Med"},{"issue":"17","key":"665_CR4","doi-asserted-by":"publisher","first-page":"1426","DOI":"10.1182\/blood.2023020075","volume":"142","author":"JE Amengual","year":"2023","unstructured":"Amengual JE, Pro B. How i treat posttransplant lymphoproliferative disorder. Blood. 2023;142(17):1426\u201337.","journal-title":"Blood"},{"key":"665_CR5","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1186\/s40164-017-0087-0","volume":"6","author":"R Bishnoi","year":"2017","unstructured":"Bishnoi R, Bajwa R, Franke AJ, Skelton WP, Wang Y, Patel NM, et al. Post-transplant lymphoproliferative disorder (PTLD): single institutional experience of 141 patients. Exp Hematol Oncol. 2017;6:26.","journal-title":"Exp Hematol Oncol"},{"issue":"25","key":"665_CR6","doi-asserted-by":"publisher","first-page":"2433","DOI":"10.1056\/NEJMoa1706640","volume":"377","author":"FM Marty","year":"2017","unstructured":"Marty FM, Ljungman P, Chemaly RF, Maertens J, Dadwal SS, Duarte RF, et al. Letermovir prophylaxis for cytomegalovirus in hematopoietic-cell transplantation. N Engl J Med. 2017;377(25):2433\u201344.","journal-title":"N Engl J Med"},{"issue":"1","key":"665_CR7","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1182\/blood.2020009396","volume":"138","author":"D Zamora","year":"2021","unstructured":"Zamora D, Duke ER, Xie H, Edmison BC, Akoto B, Kiener R, et al. Cytomegalovirus-specific T-cell reconstitution following letermovir prophylaxis after hematopoietic cell transplantation. Blood. 2021;138(1):34\u201343.","journal-title":"Blood"},{"key":"665_CR8","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2023012008","author":"CD Lauruschkat","year":"2024","unstructured":"Lauruschkat CD, Muchsin I, Rein AF, Erhard F, Grathwohl D, D\u00f6lken L, et al. Impaired T and \u201cmemory-like\u201d NK-cell reconstitution is linked to late-onset HCMV reactivation after letermovir cessation. Blood Adv. 2024. https:\/\/doi.org\/10.1182\/bloodadvances.2023012008.","journal-title":"Blood Adv."},{"issue":"9","key":"665_CR9","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1038\/s41577-019-0180-1","volume":"19","author":"JJ Goronzy","year":"2019","unstructured":"Goronzy JJ, Weyand CM. Mechanisms underlying T cell ageing. Nat Rev Immunol. 2019;19(9):573\u201383.","journal-title":"Nat Rev Immunol"},{"issue":"23","key":"665_CR10","doi-asserted-by":"publisher","first-page":"3225","DOI":"10.1182\/blood.2020009482","volume":"137","author":"Y Deng","year":"2021","unstructured":"Deng Y, Chatterjee B, Zens K, Zdimerova H, M\u00fcller A, Schuhmachers P, et al. CD27 is required for protective lytic EBV antigen-specific CD8+ T-cell expansion. Blood. 2021;137(23):3225\u201336.","journal-title":"Blood"},{"issue":"12","key":"665_CR11","first-page":"1","volume":"51","author":"T-S Kim","year":"2019","unstructured":"Kim T-S, Shin E-C. The activation of bystander CD8+ T cells and their roles in viral infection. Exp Mol Med. 2019;51(12):1\u20139.","journal-title":"Exp Mol Med"},{"key":"665_CR12","doi-asserted-by":"publisher","first-page":"1047661","DOI":"10.3389\/fimmu.2022.1047661","volume":"13","author":"N Holay","year":"2022","unstructured":"Holay N, Kennedy BE, Murphy JP, Konda P, Giacomantonio M, Brauer-Chapin T, et al. After virus exposure, early bystander na\u00efve CD8 T cell activation relies on NAD+ salvage metabolism. Front Immunol. 2022;13:1047661.","journal-title":"Front Immunol"}],"container-title":["Experimental Hematology &amp; Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40164-025-00665-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40164-025-00665-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40164-025-00665-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T12:20:44Z","timestamp":1747225244000},"score":1,"resource":{"primary":{"URL":"https:\/\/ehoonline.biomedcentral.com\/articles\/10.1186\/s40164-025-00665-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,14]]},"references-count":12,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["665"],"URL":"https:\/\/doi.org\/10.1186\/s40164-025-00665-0","relation":{},"ISSN":["2162-3619"],"issn-type":[{"value":"2162-3619","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,14]]},"assertion":[{"value":"3 January 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 May 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 May 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was approved by the Institutional Review Board of each participating hospital and was conducted in accordance with the Declaration of Helsinki and its amendments. The requirement for written informed consent was waived, owing to the non-interventional and retrospective nature of the study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"72"}}