{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:43:31Z","timestamp":1791996211591,"version":"4.4.0"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,2,16]],"date-time":"2021-02-16T00:00:00Z","timestamp":1613433600000},"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. Immunol."],"abstract":"<jats:p>Reactivation of cytomegalovirus (CMV) or Epstein-Barr virus (EBV) is common after hematopoietic stem cell transplantation (HSCT). Previous researches have demonstrated that either CMV or EBV reactivation is associated with poor outcomes of HSCT. However, few studies investigate the impact of CMV and EBV co-reactivation after HSCT. In this study, we described the clinical characteristics of HSCT recipients with CMV and EBV co-reactivation (defined as CMV and EBV viremia occur at the same period of time). We conducted a longitudinal study of 247 patients who underwent HSCT in our center. A total of 24 (9.7%) patients had CMV and EBV co-reactivation. These patients showed higher incidence of viral pneumonitis (P=0.005). Patients with CMV and EBV co-reactivation had significant lower 1-year overall survival (OS) (P=0.004) and lower 1-year leukemia free survival (LFS) (P=0.016). Our further analysis suggested that duration of CMV (P=0.014), EBV (P&amp;lt;0.001), and CD4+CD25+ T cell counts at day 30 post-transplantation (P=0.05) are independent risk factors of virus co-reactivation. In conclusion, patients who developed co-reactivation of CMV and EBV had poor prognosis in terms of lower 1-year OS and LFS, and the CMV and EBV co-reactivation was associated with prolonged CMV or EBV duration and poor CD4+CD25+ T cell reconstitution at day 30 post-transplantation.<\/jats:p>","DOI":"10.3389\/fimmu.2020.620891","type":"journal-article","created":{"date-parts":[[2021,2,18]],"date-time":"2021-02-18T17:50:46Z","timestamp":1613670646000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":39,"title":["Co-Reactivation of Cytomegalovirus and Epstein-Barr Virus Was Associated With Poor Prognosis After Allogeneic Stem Cell Transplantation"],"prefix":"10.3389","volume":"11","author":[{"given":"Jing-Rui","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da-Yu","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen-Hua","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Hui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan-Ping","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai-Yan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Jun","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Qian","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,2,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-10-748426","article-title":"The cumulative burden of double-stranded DNA virus detection after allogeneic HCT is associated with increased mortality","volume":"129","author":"Hill","year":"2017","journal-title":"Blood"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2015.06.009","article-title":"Patients with refractory cytomegalovirus (CMV) infection following allogeneic haematopoietic stem cell transplantation are at high risk for CMV disease and non-relapse mortality","volume":"21","author":"Liu","year":"2015","journal-title":"Clin Microbiol Infect"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2009.06.019","article-title":"Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective","volume":"15","author":"Tomblyn","year":"2009","journal-title":"Biol Blood Marrow Transplant"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(15)00289-6","article-title":"Cytomegalovirus viral load and mortality after haemopoietic stem cell transplantation in the era of pre-emptive therapy: a retrospective cohort study","volume":"3","author":"Green","year":"2016","journal-title":"Lancet Haematol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1093\/cid\/cit391","article-title":"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","volume":"57","author":"Styczynski","year":"2013","journal-title":"Clin Infect Dis"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2015.07.035","article-title":"Epstein-Barr Virus-Related Post-Transplantation Lymphoproliferative Disorder after Unmanipulated Human Leukocyte Antigen Haploidentical Hematopoietic Stem Cell Transplantation: Incidence, Risk Factors, Treatment, and Clinical Outcomes","volume":"21","author":"Xu","year":"2015","journal-title":"Biol Blood Marrow Transplant"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-02-487074","article-title":"CMV reactivation after allogeneic HCT and relapse risk: evidence for early protection in acute myeloid leukemia","volume":"122","author":"Green","year":"2013","journal-title":"Blood"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1097\/MOH.0000000000000083","article-title":"Epstein-Barr virus lymphoproliferative disease after hematopoietic stem cell transplant","volume":"21","author":"Rouce","year":"2014","journal-title":"Curr Opin Hematol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2012.79","article-title":"A novel protocol for haploidentical hematopoietic SCT without in vitro T-cell depletion in the treatment of severe acquired aplastic anemia","volume":"47","author":"Xu","year":"2012","journal-title":"Bone Marrow Transplant"},{"key":"B10","doi-asserted-by":"publisher","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":"B11","article-title":"1994 Consensus Conference on Acute GVHD Grading","volume":"15","author":"Przepiorka","year":"1995","journal-title":"Bone Marrow Transplant"},{"key":"B12","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1097\/00007890-197410000-00001","article-title":"Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors","volume":"18","author":"Glucksberg","year":"1974","journal-title":"Transplantation"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1111\/ctr.12172","article-title":"Epstein-Barr virus reactivation in allogeneic stem cell transplantation is highly related to cytomegalovirus reactivation","volume":"27","author":"Zallio","year":"2013","journal-title":"Clin Transplant"},{"key":"B14","article-title":"Clinical outcomes of allogeneic hematopoietic stem cell transplantation patients with co-activation of cytomegalovirus and Epstein-Barr virus","volume":"94","author":"Song","year":"2014","journal-title":"Zhonghua Yi Xue Za Zhi"},{"key":"B15","first-page":"78","article-title":"Risk Factors For The Development Of Cytomegalovirus Disease After Allogeneic Stem Cell Transplantation","volume":"9","author":"Nathan Cantoni","year":"2006","journal-title":"Haematologica"},{"key":"B16","article-title":"Cytomegalovirus infection after bone marrow transplantation: an association with acute graft-v-host disease","volume":"674","author":"Miller","year":"1986","journal-title":"Blood"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2010.03.020","article-title":"Evidence for a bidirectional relationship between cytomegalovirus replication and acute graft-versus-host disease","volume":"16","author":"Cantoni","year":"2010","journal-title":"Biol Blood Marrow Transplant"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.10751","article-title":"Retrospective evaluation of serum Epstein Barr virus DNA levels in 406 allogeneic stem cell transplant patients","volume":"96","author":"Juvonen","year":"2007","journal-title":"Haematologica"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2014.08.010","article-title":"Cytomegalovirus infection in patients who underwent allogeneic hematopoietic stem cell transplantation in Portugal: a five-year retrospective review","volume":"20","author":"Sousa","year":"2014","journal-title":"Biol Blood Marrow Transplant"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2016.05.014","article-title":"Risk Factors and Utility of a Risk-Based Algorithm for Monitoring Cytomegalovirus, Epstein-Barr Virus, and Adenovirus Infections in Pediatric Recipients after Allogeneic Hematopoietic Cell Transplantation","volume":"22","author":"Rustia","year":"2016","journal-title":"Biol Blood Marrow Transplant"},{"key":"B21","doi-asserted-by":"publisher","first-page":"18","DOI":"10.3109\/08820139.2012.719563","article-title":"Reconstitution and phenotype of Tregs in CMV reactivating patients following allogeneic hematopoietic stem cell transplantation","volume":"42","author":"Velaga","year":"2013","journal-title":"Immunol Invest"},{"key":"B22","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1007\/s12185-011-0976-7","article-title":"Impaired regulatory T cell reconstitution in patients with acute graft-versus-host disease and cytomegalovirus infection after allogeneic bone marrow transplantation","volume":"95","author":"Ngoma","year":"2012","journal-title":"Int J Hematol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2010.04.011","article-title":"Recovery of CMV-specific CD8+ T cells and Tregs after allogeneic peripheral blood stem cell transplantation","volume":"17","author":"Pastore","year":"2011","journal-title":"Biol Blood Marrow Transplant"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.21445","article-title":"Regulatory T cell activity in primary and persistent Epstein-Barr virus infection","volume":"81","author":"Wingate","year":"2009","journal-title":"J Med Virol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2020.620891\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,18]],"date-time":"2021-02-18T17:50:50Z","timestamp":1613670650000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2020.620891\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,16]]},"references-count":24,"alternative-id":["10.3389\/fimmu.2020.620891"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2020.620891","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,16]]},"article-number":"620891"}}