An update on the treatment of pediatric-onset Langerhans cell histiocytosis through pharmacotherapy

ABSTRACT

Introduction: Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasia driven by activation mutations alongside the MAPK pathway. Its broad spectrum of clinical manifestations and diverse course and clinical outcome, make interpretation of trial data difficult. Use of different stratification systems further complicates comparison among trials.

Areas covered: This review summarizes the published data derived from prospective clinical trials from Phase II onwards. PubMed was searched using combinations of the keywords ‘Langerhans cell histiocytosis’, ‘histiocytosis X’, ‘pediatric’, ‘children’, ‘treatment’, and ‘therapy’. Only full-length papers published in English and German were included in the review.

Expert opinion: Mortality in multisystem LCH is restricted to patients with involvement of risk organs (hematopoiesis, liver and spleen) at diagnosis, and is particularly high (up to 60–70%) if systemic therapy fails to control the disease. For the rest of the cohort, mortality is almost negligible, and the main challenges are disease relapses and related permanent consequences (encountered in up to 50% of the survivors). While systemic therapy has clearly improved survival of patients with most severe disease form, its role in providing sustained disease control and preventing permanent consequences in patients with ‘low risk’ disease is less clear.

KEYWORDS:

• Langerhans cell histiocytosis
• children
• treatment
• therapy
• prednisolone
• vinblastine

Article highlights

• LCH is clonal neoplastic disease with extremely variable presentation, severity, course and outcome

• Disseminated disease (e.g. multifocal skeletal or multisystem LCH) is an indication for risk-adapted systemic treatment

• The combination of vinblastine and prednisolone given in a more intensive initial 6–12 week phase followed by a less intensive continuation phase to a total treatment duration for 12 months is the current first-line standard of care

• Second-line treatment regimens are less well defined and should be provided in the frame of controlled prospective trials

• According to preliminary experience, MAPK inhibitors show excellent activity, swift dramatic response, and good tolerability in children with severe LCH failing first-line treatment

• New insights into the pathobiology suggest MAPK inhibitors as a rational treatment for the neurodegenerative type of CNS-LCH

Declaration of interest

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This manuscript has not been funded.