{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T12:24:39Z","timestamp":1787055879928,"version":"build-2736575974"},"reference-count":36,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Investigation"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>Pediatric Epstein\u2013Barr virus (EBV)\u2010associated hemophagocytic lymphohistiocytosis (HLH) is a life\u2010threatening disorder, and early identification of poor responders is critical to improving survival. However, no convenient clinical tools exist to predict individual prognosis using dynamic biomarkers during early treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate the predictive value of early dynamic changes in plasma biomarkers and to develop a prognostic model for children with EBV\u2010HLH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective study enrolled 60 newly diagnosed pediatric EBV\u2010HLH patients. We analyzed the longitudinal changes in plasma EBV\u2010DNA (pEBV\u2010DNA), ferritin, and cytokine levels during the etoposide\u2010based induction first\u2010line therapy. Independent prognostic factors were identified using Cox multivariate regression and LASSO, followed by the construction of a prognostic nomogram. Model performance was evaluated through area under the curve (AUC), decision curve analysis, and internal cross\u2010validation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Multivariate analysis identified positive pEBV\u2010DNA at week 2 (w2) and low decreases in ferritin (\u0394Ferritin.w2) and interferon (IFN)\u2010\u03b3 (\u0394IFN\u2010\u03b3.w2) as independent predictors of adverse outcomes. A nomogram integrating these three variables demonstrated a superior AUC of 0.834 (vs. 0.677 for pEBV\u2010DNA.w2 alone,\n                      <jats:italic>P<\/jats:italic>\n                      = 0.003). The model successfully stratified patients into low\u2010 and high\u2010risk groups with significantly different 3\u2010year event\u2010free survival (84.8% vs. 33.3%,\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>The proposed model, based on dynamic plasma biomarkers, provides a promising tool for the early risk stratification of pediatric EBV\u2010HLH. Composed of pEBV\u2010DNA, \u0394Ferritin, and \u0394IFN\u2010\u03b3 at w2, this nomogram can effectively identify patients at high risk of first\u2010line treatment failure. Given the exploratory nature of this study, these findings require further validation in larger, independent cohorts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ped4.70071","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T11:32:08Z","timestamp":1787052728000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dynamic early biomarkers predict outcomes in pediatric Epstein\u2013Barr virus\u2010associated hemophagocytic lymphohistiocytosis"],"prefix":"10.1002","author":[{"given":"Feifei","family":"Liu","sequence":"first","affiliation":[{"name":"Laboratory of Hematologic Diseases Beijing Pediatric Research Institute Beijing Children's Hospital Capital Medical University National Center for Children's Health  Beijing China"},{"name":"National Key Discipline of Pediatrics Capital Medical University  Beijing China"},{"name":"Key Laboratory of Major Diseases in Children 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