Langerhans cell histiocytosis
ICD-10 C96.5 · ICD-11 2B31.2

Treatment of Langerhans Cell Histiocytosis with LCH-Associated Sclerosing Cholangitis (BRAF-V600E Negative)

This protocol covers adult patients with Langerhans cell histiocytosis presenting with LCH-associated sclerosing cholangitis and critical liver involvement, who test negative for the BRAF-V600E mutation.

Clinical Scenario

LCH-associated sclerosing cholangitis represents significant liver involvement in LCH. The optimum therapy for this presentation is not established. Outcomes with chemotherapy are poor, making the choice of approach particularly consequential. BRAF-V600E mutational status informs both diagnosis and treatment planning and should be assessed in all patients — this protocol applies to those who test negative.

Treatment Approach (Partial Overview)

In the BRAF-V600E negative setting, MEK inhibitor-based targeted therapy is a central element of the approach; for patients with critical liver involvement who are otherwise fit, early liver transplant referral is also part of the management strategy. The full evidence-based regimen — including agent selection, initiation guidance, and sequencing — is in the structured protocol below.

Treatment Goals

Disease response is assessed using FDG-PET-based imaging after 2–3 months of therapy initiation, with subsequent imaging frequency individualised to the clinical situation.

Instant Access to Structured Evidence-Based Regimens

References

DOI: 10.1182/blood.2021014343
  • 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.
  • 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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