{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T10:10:18Z","timestamp":1790244618305,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T00:00:00Z","timestamp":1763337600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T00:00:00Z","timestamp":1763337600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP18ck0106462"],"award-info":[{"award-number":["JP18ck0106462"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP21ck0106717"],"award-info":[{"award-number":["JP21ck0106717"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Epstein\u2013Barr virus\u2010associated hemophagocytic lymphohistiocytosis (EBV\u2010HLH) is highly prevalent in Asia. This study evaluated the safety and efficacy of a risk\u2010stratified treatment guided by dexamethasone (DEX) response and plasma EBV\u2010DNA levels. Our goal was to optimize etoposide dosing and establish a safer EBV\u2010HLH treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a single\u2010arm, multicenter, risk\u2010stratified Phase II clinical trial, EBV\u2010HLH15, for EBV\u2010HLH. Patients were classified into three groups based on age, DEX response, and plasma EBV\u2010DNA load. In the low\u2010risk (LR) group, etoposide was eliminated from the treatment regimen. In the intermediate\u2010risk and high\u2010risk group (IR\/HR group), etoposide dosing was reduced by up to 60% compared with the HLH\u20102004 study to attenuate treatment intensity, whereas rituximab was added in the HR group to maintain it.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of 56 patients suspected of EBV\u2010HLH enrolled, 26 (14 in LR, eight in IR, and four in HR group) were eligible for EBV\u2010HLH15. The median age was 3.5\u00a0years (range: 1.0\u20138.0). The 1\u2010year overall survival of the LR and IR\/HR groups was 100% and 81.5% (95% confidence interval [CI]\u00a0=\u00a043.5\u201395.1), respectively. The event\u2010free survival of the LR and IR\/HR groups was 78.6% (95% CI\u00a0=\u00a047.2\u201392.5) and 58.3% (95% CI\u00a0=\u00a027.0\u201380.1), respectively. Most events (9\/10, mainly deterioration or recurrence of HLH) occurred within 3\u00a0weeks of treatment initiation. No patients received rituximab as scheduled in Weeks 5 and 6.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Risk\u2010stratified treatment for EBV\u2010HLH guided by DEX response and plasma EBV\u2010DNA levels after 2\u00a0weeks of treatment was safe and effective.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pbc.32166","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T08:23:37Z","timestamp":1763367817000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Risk\u2010Stratified Phase II Clinical Trial for Epstein\u2013Barr Virus\u2010Associated Hemophagocytic Lymphohistiocytosis in Pediatric, Adolescent, and Young Adult Patients in Japan"],"prefix":"10.1002","volume":"73","author":[{"given":"Kenichi","family":"Sakamoto","sequence":"first","affiliation":[{"name":"Department of Pediatrics Shinshu University School of Medicine  Matsumoto Japan"},{"name":"HLH\/LCH Committee Japan Children's Cancer Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4012-0958","authenticated-orcid":false,"given":"Ryu","family":"Yanagisawa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Shinshu University School of Medicine  Matsumoto Japan"},{"name":"HLH\/LCH Committee Japan Children's Cancer Group"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8847-2528","authenticated-orcid":false,"given":"Rintaro","family":"Ono","sequence":"additional","affiliation":[{"name":"HLH\/LCH Committee Japan Children's Cancer Group"},{"name":"Department of Pediatrics St. Luke's International Hospital  Tokyo 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