{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T12:10:43Z","timestamp":1781784643140,"version":"3.54.5"},"reference-count":38,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,8,31]],"date-time":"2025-08-31T00:00:00Z","timestamp":1756598400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Langerhans cell histiocytosis (LCH) is a rare malignancy driven by MAPK pathway activation and often involves <jats:italic>BRAF<\/jats:italic> V600E mutations. Targeted therapy with trametinib, a MEK inhibitor, is a promising alternative to conventional chemotherapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Procedure<\/jats:title><jats:p>We retrospectively analyzed the records of patients treated with trametinib either at relapse or as front\u2010line therapy between 2020 and 2024.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Fifteen pediatric patients received trametinib either at diagnosis (<jats:italic>n<\/jats:italic> = 6), relapse (<jats:italic>n<\/jats:italic> = 7), or due to chemotherapy intolerance (<jats:italic>n<\/jats:italic> = 2). Molecular testing identified MAPK pathway mutations in 11 patients. The median age at treatment initiation was 5\u00a0years (range: 0.1\u201316.5). Notably, five of these patients started trametinib before the age of 1. The median treatment duration was 2.2\u00a0years (range: 0.1\u20134.7\u00a0years). All 15 patients achieved favorable responses without concerns regarding growth and development. The adverse effects included rash (40%) and diarrhea (13%), which were all mild and were managed with temporary dose adjustments. A self\u2010weaning dosing strategy minimized long\u2010term exposure while maintaining disease control.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our data suggest that trametinib is a safe and effective therapy for pediatric LCH with broad efficacy and tolerability. However, prospective studies are needed to confirm these findings and refine targeted treatment protocols.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.32016","type":"journal-article","created":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T06:25:36Z","timestamp":1756707936000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Targeted Therapy in Pediatric Langerhans Cell Histiocytosis: Describing a Novel Strategy to Minimize Long\u2010Term Exposure While Maintaining Efficacy"],"prefix":"10.1002","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-1215-0523","authenticated-orcid":false,"given":"Natalia","family":"Wojciechowska","sequence":"first","affiliation":[{"name":"Cook Children's Medical Center  Fort Worth Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0651-4187","authenticated-orcid":false,"given":"Alexandra 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