INTRODUCTION

Background

The treatment of Langerhans cell histiocytosis (LCH) has varied greatly over the past century, and is still controversial. Early treatment approaches reflected contemporary views on disease pathogenesis, which included granulomatous, inflammatory or infectious origins for LCH. Consequently, children with LCH were treated with antibiotics, anti-inflammatory agents including steroids, and with radiation therapy and over the last 30–40 years with cytotoxic chemotherapy. While varying degrees of success have been reported, it remains true that only once the issues of aetiology and pathogenesis have been resolved can a definitive therapy be envisioned. Nevertheless, systematic approaches to diagnosis and treatment, which were major advances of the 1980s, have improved the outlook for children with LCH and are the main focus of this chapter.

Historical perspective

The first systematic treatment trial of children with LCH was that of Lahey (1962). In that study, children were matched for age and extent of disease, and outcome was analysed according to whether or not ‘specific’ treatment for LCH was given. Treatment was not controlled however, and a variety of agents, including antibiotics, steroids and cytotoxic drugs were given, making direct comparisons problematic. Nevertheless, the principal, and important, finding of this study was a significant increase in survival in the group of children receiving therapy compared to those who were untreated.

These findings led to a number of studies in which, unfortunately, the patient populations varied greatly with respect to extent of disease. This variability made interpretation of results difficult, and conclusions regarding superior treatment approaches were at best tenuous.