Disease response criteria in Langerhans cell histiocytosis: a global view

Abstract

Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasm with heterogeneous presentations. The discovery of BRAFV600E and other MAPK pathway mutations drastically transformed the treatment landscape, especially for high-risk LCH and CNS-LCH. While treatment strategies for children and adults are somewhat similar, response assessment methodologies remain highly dichotomized.Currently, separate treatment response criteria exist for children and adults, especially in therapeutic trials. Considering the rapid evolution of targeted MAPK-inhibitor therapies, along with ultrasensitive detection of minimal residual disease biomarkers (e.g., circulating BRAFV600E-encoding DNA) and sophisticated imaging tools (18F-FDG-PET and whole-body MRI), harmonization of response criteria in LCH is clearly warranted. The Histiocyte Society Global LCH Treatment Response Harmonization Task Force, a collaborative network of pediatric and adult LCH experts, is set to propose updated pediatric LCH treatment response criteria, which will also serve as the foundation for a universal response assessment tool for pediatric and adult LCH. In this review, we focus on the past, present, and likely future of response assessment in LCH patients, and discuss needs that remain unmet in the targeted therapy era.

Keywords: Harmonization; Langerhans cell histiocytosis; Response; Therapy.