Modified LCH-III Regimen With or Without Luvometinib for Multisystem Pediatric Langerhans Cell Histiocytosis

Inclusion Criteria: 1. Children aged 0-18 years, of either sex. 2. Pathologically confirmed diagnosis of Langerhans cell histiocytosis (LCH) with positive staining for CD1a and/or CD207 (Langerin), and no prior treatment specifically directed against LCH. 3. Multisystem involvement of LCH, as determined by clinical and imaging evaluation. 4. Provision of written informed consent (by parent/legal guardian and, where appropriate, assent from the child), with willingness to comply with the study treatment regimen and follow-up assessments. Exclusion Criteria: 1. Presence of any other significant underlying medical condition, including but not limited to primary immunodeficiency disorders, congestive heart failure, renal insufficiency, chronic viral hepatitis, HIV infection, or status post solid organ transplantation. 2. History of a second (secondary) malignancy. 3. QTcF interval \> 0.47 seconds on electrocardiogram performed prior to enrollment. 4. Ophthalmologic screening prior to enrollment revealing retinal vein occlusion, retinal pigment epithelial detachment, or other clinically significant ocular abnormalities that, in the opinion of the investigator, contraindicate participation. 5. LCH harboring Class 3 MEK pathway mutations, specifically the following alterations: L98\_I103del, L98\_K104del, P105\_A106del, P105\_I107delinsL, L101\_I103delinsF, E102\_I103delinsF, E102\_I103del, E102\_I103delinsV, E102\_I103delinsVN, E102\_K104delinsQ, or I103\_A106del. 6. Refusal or inability to provide written informed consent (or assent, as applicable).