{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T12:17:40Z","timestamp":1780316260574,"version":"3.54.1"},"reference-count":36,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"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 Blood &amp;amp; Cancer"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Standardized salvage treatments for refractory\/relapse Langerhans cell histiocytosis (LCH) remain to be established. Trametinib (TRA) has shown marked efficacy in LCH, but cohort studies regarding efficacy and safety of TRA monotherapy in refractory\/relapse LCH were scarce.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods\/Results<\/jats:title>\n                    <jats:p>We retrospectively analyzed 22 patients with refractory\/relapse LCH treated with TRA monotherapy. Patients were treated for a median of 21.4 months (3.0\u201351.6 months). Nineteen (86.4%) of 22 of patients remained progression\u2010free during TRA treatment. Sixteen patients stopped TRA (not due to progression or toxicity), of which 10 remained progression free, with median follow\u2010up time of 28.7 months (1.5\u201344.6 months) after TRA withdrawal, and 6 patients experienced relapse, with median time to relapse from post\u2010TRA withdrawal of 3.7 months (2.7\u201316.5 months). Two patients continued on TRA at last follow\u2010up and one switched to chemotherapy due to toxicity. Three\u2010year event\u2010free survival was 50.7% (95% CI: 27.7\u201369.8), with a median follow\u2010up time of 36.4 months (3.0\u201367.6 months). From TRA initiation to 12 months of treatment, cell\u2010free BRAF\/MAP2K1 mutation status in blood presented as negative to negative or positive to negative was correlated with superior event\u2010free survival rate (EFS) rate. Toxicity was tolerable, and adverse events were predominantly skin rash (77.3%), paronychia (22.7%), and diarrhea (13.6%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Overall, TRA was effective and safe in the treatment of patients with refractory\/relapse LCH, offering a convenient therapeutic alternative.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/1545-5017.70162","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T10:56:36Z","timestamp":1773399396000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Trametinib Monotherapy in the Treatment of Pediatric Refractory\/Relapse Langerhans Cell Histiocytosis"],"prefix":"10.1002","volume":"73","author":[{"given":"Wenqian","family":"Wang","sequence":"first","affiliation":[{"name":"Hematology Center Beijing Children's Hospital Capital Medical University, National Center for Children's Health  Beijing China"},{"name":"Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics Capital Medical University  Beijing China"},{"name":"Key Laboratory of Major Diseases in Children Ministry of Education  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zishi","family":"Fang","sequence":"additional","affiliation":[{"name":"Hematology Center Beijing Children's Hospital Capital Medical University, National Center for Children's Health  Beijing China"},{"name":"Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics Capital Medical University  Beijing China"},{"name":"Key Laboratory of Major Diseases in Children Ministry of Education  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Ge","sequence":"additional","affiliation":[{"name":"Hematology Center 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Wang","sequence":"additional","affiliation":[{"name":"Hematology Center Beijing Children's Hospital Capital Medical University, National Center for Children's Health  Beijing China"},{"name":"Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics Capital Medical University  Beijing China"},{"name":"Key Laboratory of Major Diseases in Children Ministry of Education  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Cui","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics Capital Medical University  Beijing China"},{"name":"Key Laboratory of Major Diseases in Children Ministry of Education  Beijing China"},{"name":"Hematologic Disease Laboratory Beijing Pediatric Research Institute Beijing Children's Hospital Capital Medical University, National Center For Children's Health  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenxin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Hematology Center Beijing Children's Hospital Capital Medical University, National Center for Children's Health  Beijing China"},{"name":"Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics Capital Medical University  Beijing China"},{"name":"Key Laboratory of Major Diseases in Children Ministry of Education  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhigang","family":"Li","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics Capital Medical University  Beijing China"},{"name":"Key Laboratory of Major Diseases in Children Ministry of Education  Beijing China"},{"name":"Hematologic Disease Laboratory Beijing Pediatric 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