Children with Langerhans cell histiocytosis (LCH) develop destructive lesions that can arise in virtually any organ including bone, brain, liver and bone marrow. LCH was first identified over 100 years ago, but only in the past ~10 years has been recognized as a disease in the family of pediatric cancers. The current standard of care for children with systemic LCH is chemotherapy that fails to cure over 50%, and the majority of patients who are cured suffer long term consequences.
Improved therapies are clearly needed for children with LCH. A mutation in the BRAF gene (called BRAF-V600E), was discovered in over half of LCH tumors. Subsequently, more mutations in genes in the MAPK pathway have been discovered in almost all cases of LCH. Studies in blood cells from patients with LCH and in mice demonstrated that LCH is caused by activation of the MAPK pathway at specific stages of blood cell development.
We have organized a team consisting of international leaders in immunology/tumor biology, genomics and pediatric oncology research to create the North American Consortium for Histiocytosis (NACHO). New biological insights and development of the NACHO consortium create potential to transform outcomes for patients with LCH.
This study aims to test a novel therapy that blocks the abnormal growth from the MAPK pathway and also uses chemotherapy. The study is testing the hypothesis that this novel combination will cure patients.
