{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:22:51Z","timestamp":1787163771258,"version":"build-2736575974"},"reference-count":29,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"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":["European J of Haematology"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Secondary hemophagocytic lymphohistiocytosis (sHLH) is a severe hyperinflammatory syndrome requiring rapid recognition and treatment. Despite the expanding availability of biologic and cytokine\u2010directed therapies, etoposide\u2010based immunochemotherapy remains the primary treatment in many pediatric centers. This study evaluated the efficacy, response kinetics, and clinical outcomes of etoposide\u2010based therapy in children with sHLH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively analyzed 32 pediatric patients diagnosed with sHLH between 2018 and 2023 at a tertiary center. Diagnosis was based on HLH\u20102004 criteria; primary HLH was excluded through genetic testing when available. All patients received dexamethasone and etoposide, with cyclosporine A initiated after Week 1. Trigger\u2010directed therapies included rituximab for EBV\u2010HLH and anakinra or tocilizumab in selected hyperinflammatory states. Laboratory dynamics (ferritin, fibrinogen, platelets, and absolute neutrophil count), clinical responses, relapse, hematopoietic stem cell transplantation (HSCT), and overall survival (OS) were assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The median age was 38\u2009months; 62.5% were male. Triggers included EBV (34%), other viral infections (19%), rheumatologic disease\/MAS (16%), bacterial infection (13%), and malignancy (9%). By Week 4, ferritin decreased from 6480 to 1240\u2009ng\/mL and fibrinogen increased from 122 to 286\u2009mg\/dL (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Fever resolved in 90% by Week 2, and 81% achieved complete laboratory response. During a median follow\u2010up of 18\u2009months, relapse occurred in 18.8% and HSCT was required in 15.6% of patients. Overall survival was 91% at 1\u2009year and 86% at 2\u2009years. Adverse events were consistent with expected etoposide\u2010related toxicities.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Etoposide\u2010based immunochemotherapy provided rapid disease control and favorable survival in pediatric sHLH. These findings support the continued relevance of etoposide while underscoring the need for risk\u2010adapted approaches integrating trigger\u2010directed therapy, cytokine inhibitors, and timely HSCT in selected patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ejh.70082","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T23:49:21Z","timestamp":1765928961000},"page":"319-325","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Efficacy of Etoposide\u2010Based Therapy in Pediatric Secondary Hemophagocytic Lymphohistiocytosis"],"prefix":"10.1111","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6939-1570","authenticated-orcid":false,"given":"Neryal","family":"Tahta","sequence":"first","affiliation":[{"name":"Department of Pediatric Hematology and Oncology Izmir City Hospital  Izmir Turkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5768-0890","authenticated-orcid":false,"given":"Sultan Okur","family":"Acar","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology Dokuz Eylul University  Izmir Turkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4292-1409","authenticated-orcid":false,"given":"I\u015f\u0131k Odaman","family":"Al","sequence":"additional","affiliation":[{"name":"Ba\u011fc\u0131lar Medipol Mega Hospital  Istanbul Turkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5365-8103","authenticated-orcid":false,"given":"Melek","family":"Erdem","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Department of Pediatric Hematology and Oncology Istinye University  Istanbul Turkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4714-332X","authenticated-orcid":false,"given":"Tu\u011fba Hilkay","family":"Karap\u0131nar","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology Dr Behcet Uz Children's Hospital  Izmir Turkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6908-8309","authenticated-orcid":false,"given":"Ye\u015fim","family":"Oymak","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology Dr Behcet Uz Children's Hospital  Izmir Turkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8585-9628","authenticated-orcid":false,"given":"Salih","family":"G\u00f6zmen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology Izmir City Hospital  Izmir Turkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,16]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2007.05.001"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-03-278127"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2016.05.001"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2014.10.001"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation-2015.1.190"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1040-8428(02)00117-8"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2017.03.023"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.21039"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/key006"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation-2009.1.127"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-01-0172"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2013.12.012"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-04-282392"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-025-03698-0"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-911X(199705)28:5<342::AID-MPO3>3.0.CO;2-H"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2001.19.10.2665"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-06-788349"},{"issue":"29","key":"e_1_2_12_19_1","first-page":"e150","article-title":"Clinical 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