In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 25 ( 2016-09-01), p. 3023-3030
Abstract:
Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasia with a broad spectrum of clinical manifestations and outcomes in children. The somatic BRAF V600E mutation occurs frequently, but clinical significance remains to be determined. Patients and Methods BRAF V600E 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 BRAF V600E mutation. Patients with BRAF V600E manifested more severe disease than did those with wild-type BRAF. Patients with BRAF V600E 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). BRAF V600E 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 BRAF V600E 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, BRAF V600E 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.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2015.65.9508
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2016
detail.hit.zdb_id:
2005181-5
detail.hit.zdb_id:
604914-X
