Marta Wilejto1, Oussama Abla. 1. Division of Haematology/Oncology, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada. marta.wilejto@sickkids.ca
Abstract
PURPOSE OF REVIEW: To provide an updated overview of the pathogenesis and treatment of Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD). RECENT FINDINGS: There is ongoing debate as to the exact pathogenesis of these disorders and their classification as reactive versus neoplastic. Proinflammatory cytokines are known to play a role in both LCH and ECD and strengthen the hypothesis that, at least in part, they are disorders of immune dysregulation. The recent discovery of activating mutations in the proto-oncogene BRAF in a subset of LCH patients suggests that LCH is in fact a neoplastic disorder. Understanding of the mechanisms that promote proliferation and migration of histiocytes has led researchers to explore targeted immune-modulatory therapies for ECD. Similarly for LCH, alternative chemotherapeutic agents and reduced-intensity hematopoietic stem cell transplant are being evaluated for refractory disease. SUMMARY: More research is needed to better understand the cause of these disorders and may help in identifying new targeted therapies, particularly for patients with refractory or relapsed disease. Multinational trials are ongoing for LCH and are urgently needed for ECD.
PURPOSE OF REVIEW: To provide an updated overview of the pathogenesis and treatment of Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD). RECENT FINDINGS: There is ongoing debate as to the exact pathogenesis of these disorders and their classification as reactive versus neoplastic. Proinflammatory cytokines are known to play a role in both LCH and ECD and strengthen the hypothesis that, at least in part, they are disorders of immune dysregulation. The recent discovery of activating mutations in the proto-oncogene BRAF in a subset of LCH patients suggests that LCH is in fact a neoplastic disorder. Understanding of the mechanisms that promote proliferation and migration of histiocytes has led researchers to explore targeted immune-modulatory therapies for ECD. Similarly for LCH, alternative chemotherapeutic agents and reduced-intensity hematopoietic stem cell transplant are being evaluated for refractory disease. SUMMARY: More research is needed to better understand the cause of these disorders and may help in identifying new targeted therapies, particularly for patients with refractory or relapsed disease. Multinational trials are ongoing for LCH and are urgently needed for ECD.
Authors: Eli L Diamond; Lorenzo Dagna; David M Hyman; Giulio Cavalli; Filip Janku; Juvianee Estrada-Veras; Marina Ferrarini; Omar Abdel-Wahab; Mark L Heaney; Paul J Scheel; Nancy K Feeley; Elisabetta Ferrero; Kenneth L McClain; Augusto Vaglio; Thomas Colby; Laurent Arnaud; Julien Haroche Journal: Blood Date: 2014-05-21 Impact factor: 22.113
Authors: Georgi Iskrov; Itziar Astigarraga; Rumen Stefanov; Julio López-Bastida; Renata Linertová; Juan Oliva-Moreno; Pedro Serrano-Aguilar; Manuel Posada-de-la-Paz; Arrigo Schieppati; Domenica Taruscio; Márta Péntek; Johann Matthias Graf von der Schulenburg; Panos Kanavos; Karine Chevreul; Ulf Persson; Giovanni Fattore Journal: Eur J Health Econ Date: 2016-04-04
Authors: S Sirrs; P Munk; P I Mallinson; H Ouellette; G Horvath; S Cooper; G Da Roza; D Rosenbaum; M O'Riley; G Nussbaumer; L N Hoang; C H Lee Journal: JIMD Rep Date: 2013-10-06