{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T18:10:08Z","timestamp":1785175808046,"version":"3.55.0"},"reference-count":26,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T00:00:00Z","timestamp":1765929600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T00:00:00Z","timestamp":1765929600000},"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":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2026,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Langerhans cell histiocytosis (LCH) is a rare, heterogeneous inflammatory myeloid neoplasm. This study focuses to summarize real\u2010world experiences of using mitogen\u2010activated protein kinase (MAPK) inhibitors in managing pediatric LCH. Thirty\u2010six children with LCH received vemurafenib (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200911), dabrafenib (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200919), or trametinib (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20096), either as monotherapy (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200924) or combined with chemotherapy (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200912). The median Disease Activity Score declined from 5 at baseline to 1 after 3\u2009months of MAPK inhibitor therapy (\n                    <jats:italic>p\u2009&lt;<\/jats:italic>\n                    \u2009.0001). Elevated interleukin\u20102 receptor (IL\u20102R) and tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1) levels were observed in 90.1% and 81.8% of patients, respectively. Median IL\u20102R and TNF\u2010\u03b1 levels decreased from 1212\u2009U\/mL and 15 \u03c1g\/mL at baseline to 494\u2009U\/mL and 4.18 \u03c1g\/mL at 3\u2009months (\n                    <jats:italic>p\u2009&lt;<\/jats:italic>\n                    \u2009.0001,\n                    <jats:italic>p\u2009=<\/jats:italic>\n                    \u2009.002), with no significant differences between MAPK inhibitor alone and combined with chemotherapy groups (\n                    <jats:italic>p\u2009=<\/jats:italic>\n                    \u2009.7791,\n                    <jats:italic>p\u2009=<\/jats:italic>\n                    \u2009.7503). The objective response rate at 3\u2009months was 94.4% (34\/36). At last follow\u2010up, 20 patients had no active disease (NAD); 13 had NAD with residual diabetes insipidus and\/or sclerosing cholangitis; 1 had NAD with neurodegeneration; and 2 died of progressive disease. Among 13 patients who discontinued treatment, relapse occurred more frequently in the monotherapy group (75%) than in the combination group (20%), but the difference was not statistically significant (\n                    <jats:italic>p<\/jats:italic>\n                    = .103). [Correction added on 07 February 2026, after first online publication: The\n                    <jats:italic>p<\/jats:italic>\n                    value has been revised from .047 to .103.]. Grade\u2009\u22653 adverse events occurred in 11.1% and resolved with dose adjustment. MAPK inhibitors are effective and well tolerated in pediatric LCH. Combination therapy may reduce relapse risk. Further prospective studies are warranted.\n                  <\/jats:p>","DOI":"10.1002\/ijc.70300","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T03:39:12Z","timestamp":1766029152000},"page":"2674-2683","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Efficacy, safety, and relapse outcomes of\n                    <scp>MAPK<\/scp>\n                    inhibitors in pediatric Langerhans cell histiocytosis: A real\u2010world study"],"prefix":"10.1002","volume":"158","author":[{"given":"Xue","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Pediatrics, West China Second University Hospital Sichuan University  Chengdu Sichuan China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children Sichuan University, Ministry of Education  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing\u2010jing","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, West China Second University Hospital Sichuan University  Chengdu Sichuan China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children Sichuan University, Ministry of Education  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, West China Second University Hospital Sichuan University  Chengdu Sichuan China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children Sichuan University, Ministry of Education  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao\u2010yu","family":"Jing","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, West China Second University Hospital Sichuan University  Chengdu Sichuan China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children Sichuan University, Ministry of Education  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9283-3274","authenticated-orcid":false,"given":"Xia","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, West China Second University Hospital Sichuan University  Chengdu Sichuan China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children Sichuan University, Ministry of Education  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, West China Second University Hospital Sichuan University  Chengdu Sichuan China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children Sichuan University, Ministry of Education  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,17]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019000934"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-09-455774"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.19376"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-03-635151"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2024025625"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.19.00456"},{"key":"e_1_2_11_8_1","first-page":"1137","article-title":"Dabrafenib and trametinib in Langerhans cell histiocytosis and other histiocytic disorders","volume":"109","author":"Cournoyer 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