Treatment of Langerhans cell histiocytosis--evolution and current approaches.

Optimal treatment of Langerhans cell histiocytosis remains problematic. The absence of controlled studies and the lack of standard diagnostic and evaluation criteria have impeded therapeutic progress even though knowledge of basic aspects of LCH have advanced. Historical analysis of outcome suggests little improvement until very recently, but marked differences in outcome according to extent of disease. Consequently, major and now successful efforts have been made to stratify LCH patients into different 'risk groups'. Recent findings suggest that combination chemotherapy for multisystem disease is beneficial and that VP-16 is a useful new agent for treating LCH, despite controversies regarding its side effects. The first randomised international treatment study, LCH-1, being conducted by the Histiocyte Society, should resolve some of these controversies. Other experimental therapies may be considered for children with severe, unresponsive LCH.