This protocol addresses adults with Langerhans cell histiocytosis complicated by LCH-associated sclerosing cholangitis — a presentation involving critical liver involvement — in whom a BRAF-V600E mutation has been confirmed.
LCH-associated sclerosing cholangitis poses a distinct therapeutic challenge. The optimal treatment for this hepatic complication remains undefined, and standard chemotherapy has been associated with poor outcomes in this setting. BRAF-V600E mutational testing is recommended for all LCH patients to inform both diagnosis and treatment selection.
The approach centres on a BRAF inhibitor directed at the confirmed mutation, alongside early assessment of liver transplant candidacy in otherwise fit patients. The full protocol — including agent choice, dosing rationale, and transplant evaluation pathway — is available via the structured regimen below.
Treatment response is evaluated using FDG-PET–based imaging after 2–3 months of therapy initiation, with subsequent imaging frequency individualised to the clinical scenario.
For LCH-associated sclerosing cholangitis, the optimum therapy is unknown.
Due to poor outcomes with chemotherapy, targeted agents are preferable.
All patients with LCH should undergo BRAF-V600E mutational testing to aid in diagnosis and treatment.
Prolonged remissions following liver transplant have been reported; therefore, early transplant referral should be undertaken in otherwise fit patients.
Because most patients will require a dose reduction and lower doses of BRAF and MEK inhibitors are quite effective, it is reasonable to start at half of the dose currently used to treat patients with melanoma.
For initially FDG PET avid LCH, it is recommended to repeat an FDG PET-based imaging study for assessment of disease response after 2-3 mo of initiation of therapy, with subsequent imaging frequency tailored individually based on the specific clinical scenario.
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