{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:43:30Z","timestamp":1791996210613,"version":"4.4.0"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Whether simultaneous cytomegalovirus (CMV) and Epstein\u2013Barr virus (EBV) reactivation confers additional late mortality beyond isolated CMV remains controversial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively analyzed 202 consecutive first-ever hematopoietic stem cell transplantations performed between 2018 and 2019, using twice-weekly PCR surveillance and uniform preemptive therapy. Cox models were used to estimate hazard ratios (HRs) for overall survival (OS) and leukemia-free survival (LFS) at the 1-, 3-, and 5-year landmarks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Although 1-year outcomes were similar, divergence emerged thereafter: 5-year OS was 19.4% with coreactivation, 36.6% with isolated CMV, and 25.1% with no reactivation (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.041); corresponding LFS was 19.4%, 36.6%, and 25.2% (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.060). Multivariate analysis identified sustained CMV replication as the dominant late risk factor (OS HR 5.295, 95% CI 1.5888\u201317.6464;\n                      <jats:italic>p<\/jats:italic>\n                      = 0.0067), whereas coreactivation lost significance because EBV clearance shortened the overall viral window. Interestingly, viral enteritis was identified as an independent adverse predictor of 1-year LFS (HR 6.2453, 95% CI 1.3245\u20137.2376;\n                      <jats:italic>p<\/jats:italic>\n                      = 0.0010).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Late mortality is driven by persistent CMV-driven endothelial injury rather than transient EBV coreactivation. Extending PCR surveillance from day 100 to year 2 and targeting chronic low-level CMV should be prioritized to improve long-term transplantation success.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1782595","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T11:24:45Z","timestamp":1774437885000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Late-phase impact of CMV\/EBV reactivation on survival after hematopoietic stem-cell transplantation: a 5-year single-center cohort study"],"prefix":"10.3389","volume":"16","author":[{"given":"Shanshan","family":"Li","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Peking University Third Hospital","place":["Beijing, China"]},{"name":"Core Unit of National Clinical Research Center for Laboratory Medicine, Peking University Third Hospital","place":["Beijing, China"]},{"name":"Department of Clinical Laboratory, Peking University People\u2019s Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Peking University People\u2019s Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyan","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Peking University Third Hospital","place":["Beijing, China"]},{"name":"Core Unit of National Clinical Research Center for Laboratory Medicine, Peking University Third Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"43163","DOI":"10.1038\/s41598-025-27354-6","article-title":"Prophylactic infusion of donor derived CMV specific T cells for the prevention of CMV reactivation following allogeneic HSCT","volume":"15","author":"Barkhordar","year":"2025","journal-title":"Sci. Rep."},{"key":"B2","doi-asserted-by":"publisher","first-page":"798","DOI":"10.1200\/JCO.2013.51.5304","article-title":"Sustained complete responses in patients with lymphoma receiving autologous cytotoxic T lymphocytes targeting Epstein-Barr virus latent membrane proteins","volume":"32","author":"Bollard","year":"2014","journal-title":"J. Clin. Oncol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1038\/s41408-024-01116-5","article-title":"Busulfan-fludarabine versus busulfan-cyclophosphamide for allogeneic transplant in acute myeloid leukemia: long term analysis of GITMO AML-R2 trial","volume":"14","author":"Cavallaro","year":"2024","journal-title":"Blood Cancer J."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1401","DOI":"10.1038\/mt.2015.91","article-title":"Long-term outcome of extranodal NK\/T cell lymphoma patients treated with postremission therapy using EBV LMP1 and LMP2a-specific CTLs","volume":"23","author":"Cho","year":"2015","journal-title":"Mol. Ther."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1875","DOI":"10.1016\/S0140-6736(00)02293-5","article-title":"Assessment of thymic output in adults after haematopoietic stem-cell transplantation and prediction of T-cell reconstitution","volume":"355","author":"Douek","year":"2000","journal-title":"Lancet"},{"key":"B6","doi-asserted-by":"publisher","first-page":"2366","DOI":"10.1111\/ajt.15402","article-title":"Postreperfusion plasma endothelial activation markers are associated with acute kidney injury after lung transplantation","volume":"19","author":"Forker","year":"2019","journal-title":"Am. J. Transplant."},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1251593","article-title":"Prevention of CMV\/EBV reactivation by double-specific T cells in patients after allogeneic stem cell transplantation: results from the randomized phase I\/IIa MULTIVIR-01 study","volume":"14","author":"Gerbitz","year":"2023","journal-title":"Front. Immunol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"3030","DOI":"10.1016\/j.cell.2025.03.022","article-title":"Optimizing stem cell infusion timing in the prevention of acute graft-versus-host disease","volume":"188","author":"Hou","year":"2025","journal-title":"Cell"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1467","DOI":"10.1056\/NEJMoa2313812","article-title":"Sequential CD7 CAR T-cell therapy and allogeneic HSCT without GVHD prophylaxis","volume":"390","author":"Hu","year":"2024","journal-title":"N Engl. J. Med."},{"key":"B10","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1038\/s41422-022-00721-y","article-title":"Genetically modified CD7-targeting allogeneic CAR-T cell therapy with enhanced efficacy for relapsed\/refractory CD7-positive hematological Malignancies: a phase I clinical study","volume":"32","author":"Hu","year":"2022","journal-title":"Cell Res."},{"key":"B11","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/j.bbmt.2008.11.025","article-title":"Treatment of acute leukemia with unmanipulated HLA-mismatched\/haploidentical blood and bone marrow transplantation","volume":"15","author":"Huang","year":"2009","journal-title":"Biol. Blood Marrow Transplant."},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.70192","article-title":"Building a bridge between the mechanism of EBV reactivation and the treatment of EBV-associated cancers","volume":"97","author":"Jiang","year":"2025","journal-title":"J. Med. Virol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1186\/s13045-024-01612-y","article-title":"Increased Epstein\u2013Barr virus reactivation following prophylaxis for cytomegalovirus infection after haploidentical haematopoietic stem cell transplantation","volume":"17","author":"Kong","year":"2024","journal-title":"J. Hematol. Oncol."},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.818167","article-title":"Association between cytomegalovirus and epstein-barr virus co-reactivation and hematopoietic stem cell transplantation","volume":"12","author":"Li","year":"2022","journal-title":"Front. Cell Infect. Microbiol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"2199","DOI":"10.3760\/cma.j.issn.0366-6999.2010.16.008","article-title":"Valganciclovir for pre-emptive therapy of cytomegalovirus viraemia after hematopoietic stem cell transplantation: a prospective multi-center trial","volume":"123","author":"Liu","year":"2010","journal-title":"Chin. Med. J. Engl"},{"key":"B16","doi-asserted-by":"publisher","first-page":"e451","DOI":"10.1016\/S1473-3099(25)00069-6","article-title":"Recommendations from the 10th European Conference on Infections in Leukaemia for the management of cytomegalovirus in patients after allogeneic haematopoietic cell transplantation and other T-cell-engaging therapies","volume":"25","author":"Ljungman","year":"2025","journal-title":"Lancet Infect. Dis."},{"key":"B17","doi-asserted-by":"publisher","first-page":"2433","DOI":"10.1056\/NEJMoa1706640","article-title":"Letermovir prophylaxis for cytomegalovirus in hematopoietic-cell transplantation","volume":"377","author":"Marty","year":"2017","journal-title":"N Engl. J. Med."},{"key":"B18","doi-asserted-by":"publisher","first-page":"3001","DOI":"10.1182\/bloodadvances.2023011626","article-title":"Tabelecleucel for EBV+ PTLD after allogeneic HCT or SOT in a multicenter expanded access protocol","volume":"8","author":"Nikiforow","year":"2024","journal-title":"Blood Adv."},{"key":"B19","doi-asserted-by":"publisher","first-page":"2514","DOI":"10.1158\/1078-0432.CCR-08-1254","article-title":"EBV-related lymphoproliferative disease complicating therapy with the anti-CD2 monoclonal antibody, siplizumab, in patients with T-cell Malignancies","volume":"15","author":"O\u2019Mahony","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"B20","doi-asserted-by":"publisher","first-page":"2474","DOI":"10.1093\/jac\/dkaf243","article-title":"Dynamics of dual CMV and EBV co-reactivation and emergence of resistance in an HSCT recipient","volume":"80","author":"Pociupany","year":"2025","journal-title":"J. Antimicrob. Chemother."},{"key":"B21","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1172\/JCI121127","article-title":"Off-the-shelf EBV-specific T cell immunotherapy for rituximab-refractory EBV-associated lymphoma following transplantation","volume":"130","author":"Prockop","year":"2020","journal-title":"J. Clin. Invest."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02549","article-title":"Heterologous cytomegalovirus and allo-reactivity by shared T cell receptor repertoire in kidney transplantation","volume":"10","author":"Stranavova","year":"2019","journal-title":"Front. Immunol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1515\/jtim-2025-0018","article-title":"A novel and safe protocol for patients with severe comorbidity who undergo haploidentical hematopoietic stem cell transplantation: A single-center prospective study","volume":"13","author":"Sun","year":"2025","journal-title":"J. Transl. Int. Med."},{"key":"B24","doi-asserted-by":"publisher","first-page":"876","DOI":"10.3390\/pathogens13100876","article-title":"Immune modulation by epstein-barr virus lytic cycle: relevance and implication in oncogenesis","volume":"13","author":"Todorovic","year":"2024","journal-title":"Pathogens"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1181","DOI":"10.1016\/j.annonc.2024.08.2344","article-title":"Gemcitabine, carboplatin, and Epstein-Barr virus-specific autologous cytotoxic T lymphocytes for recurrent or metastatic nasopharyngeal carcinoma: VANCE, an international randomized phase III trial","volume":"35","author":"Toh","year":"2024","journal-title":"Ann. Oncol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1038\/bmt.2013.191","article-title":"Influence of two different doses of antithymocyte globulin in patients with standard-risk disease following haploidentical transplantation: a randomized trial","volume":"49","author":"Wang","year":"2014","journal-title":"Bone Marrow Transplant."},{"key":"B27","doi-asserted-by":"publisher","first-page":"3956","DOI":"10.1182\/blood-2015-02-627786","article-title":"Haploidentical vs identical-sibling transplant for AML in remission: a multicenter, prospective study","volume":"125","author":"Wang","year":"2015","journal-title":"Blood"},{"key":"B28","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/s13045-018-0564-x","article-title":"The consensus on indications, conditioning regimen, and donor selection of allogeneic hematopoietic cell transplantation for hematological diseases in China-recommendations from the Chinese Society of Hematology","volume":"11","author":"Xu","year":"2018","journal-title":"J. Hematol. Oncol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1016\/j.jare.2025.02.006","article-title":"Sequential allogeneic HSCT after CAR-T therapy for relapsed\/refractory acute lymphoblastic leukemia patients: A long-term follow-up result","volume":"78","author":"Yang","year":"2025","journal-title":"J. Adv. Res."},{"key":"B30","doi-asserted-by":"publisher","first-page":"5059","DOI":"10.2147\/DDDT.S513383","article-title":"Efficacy and safety of letermovir for cytomegalovirus prophylaxis following allogeneic hematopoietic stem cell transplantation in pediatric patients","volume":"19","author":"Zhu","year":"2025","journal-title":"Drug Des. Devel Ther."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1782595\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T11:24:47Z","timestamp":1774437887000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1782595\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,25]]},"references-count":30,"alternative-id":["10.3389\/fcimb.2026.1782595"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2026.1782595","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,25]]},"article-number":"1782595"}}