@article{Héritier2016, abstract = {Purpose Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasia with a broad spectrum of clinical manifestations and outcomes in children. The somatic BRAFV600E mutation occurs frequently, but clinical significance remains to be determined. Patients and Methods BRAFV600E mutation was investigated in a French LCH cohort. We analyzed associations between mutation status and clinical presentation, extent of disease, reactivation rate, response to therapy, and long-term permanent sequelae. Results Among 315 patients with successfully determined BRAF status, 173 (54.6%) carried a BRAFV600E mutation. Patients with BRAFV600E manifested more severe disease than did those with wild-type BRAF. Patients with BRAFV600E comprised 87.8% of patients (43 of 49) with multisystem LCH with risk organ involvement (liver, spleen, hematology), 68.6% of patients (35 of 51) with multisystem LCH without risk organ involvement, 43.9% of patients (86 of 196) with single-system LCH, and 42.1% of patients (8 of 19) with lung-involved LCH (P < .001). BRAFV600E mutation was also associated with organ involvement that could lead to permanent, irreversible damage, such as neurologic (75%) and pituitary (72.9%) injuries. Compared with patients with wild-type BRAF, patients with BRAFV600E more commonly displayed resistance to combined vinblastine and corticosteroid therapy (21.9% v 3.3%; P = .001), showed a higher reactivation rate (5-year reactivation rate, 42.8% v 28.1%; P = .006), and had more permanent, long-term consequences from disease or treatment (27.9% v 12.6%; P = .001). Conclusion In children with LCH, BRAFV600E mutation was associated with high-risk features, permanent injury, and poor short-term response to chemotherapy. Further population-based studies should be undertaken to confirm our observations and to assess the impact of BRAF inhibitors for this subgroup of patients who may benefit from targeted therapy. }, author = {Héritier, Sébastien and Emile, Jean-François and Barkaoui, Mohamed-Aziz and Thomas, Caroline and Fraitag, Sylvie and Boudjemaa, Sabah and Renaud, Florence and Moreau, Anne and Peuchmaur, Michel and Chassagne-Clément, Catherine and Dijoud, Frédérique and Rigau, Valérie and Moshous, Despina and Lambilliotte, Anne and Mazingue, Françoise and Kebaili, Kamila and Miron, Jean and Jeziorski, Eric and Plat, Geneviève and Aladjidi, Nathalie and Ferster, Alina and Pacquement, Hélène and Galambrun, Claire and Brugières, Laurence and Leverger, Guy and Mansuy, Ludovic and Paillard, Catherine and Deville, Anne and Armari-Alla, Corinne and Lutun, Anne and Gillibert-Yvert, Marion and Stephan, Jean-Louis and Cohen-Aubart, Fleur and Haroche, Julien and Pellier, Isabelle and Millot, Frédéric and Lescoeur, Brigitte and Gandemer, Virginie and Bodemer, Christine and Lacave, Roger and Hélias-Rodzewicz, Zofia and Taly, Valérie and Geissmann, Frédéric and Donadieu, Jean}, doi = {10.1200/jco.2015.65.9508}, journal = {Journal of Clinical Oncology}, month = {sep}, pages = {3023-3030}, title = {BRAF Mutation Correlates With High-Risk Langerhans Cell Histiocytosis and Increased Resistance to First-Line Therapy}, url = {http://europepmc.org/articles/pmc5321082?pdf=render}, volume = {34}, year = {2016} }