Mutation in Cell-Free DNA, Rather than in Lesion Tissues, at Diagnosis Is An Independent Prognostic Factor in Children with Langerhans Cell Histiocytosis.

The aim of this study was to investigate the prognostic significance of BRAF in cell-free (cf) DNA (cfBRAF) and lesion tissues (ltBRAF) in pediatric Langerhans cell histiocytosis (LCH). This study included a total of 140 patients with successfully detected cfBRAF and ltBRAF at diagnosis. Treatment response at week 6 was correlated with both cfBRAF and ltBRAF Moreover, the patients with positive cfBRAF had a much lower 3-year progression-free survival (PFS) rate and a higher progression/reactivation rate than those with negative cfBRAF (47.1% ± 7.6% vs. 78.4% ± 5.1%, < 0.0001; 44.6% vs. 19.0%, = 0.001, respectively). However, no significant difference was found in the 3-year PFS rate or progression/reactivation rate between patients with positive and negative ltBRAF ( = 0.348 and 0.596, respectively). In addition, after patients were divided into group A (both cfBRAF and ltBRAF positive, = 56), group B (ltBRAF positive and cfBRAF negative, = 28), and group C (both cfBRAF and ltBRAF negative, = 56), there was a significant difference in the 3-year PFS rate and progression/reactivation rate among the three groups (47.1% ± 7.6%, 92.9% ± 6.1%, and 72.2% ± 6.1%, < 0.001; 44.6%, 3.6%, and 26.8%, < 0.001, respectively). In the multivariate analysis, cfBRAF and age at diagnosis remained independent prognostic factors for 3-year PFS in childhood LCH. Therefore, cfBRAF was more closely associated with important clinical characteristics, treatment response at week 6, and prognosis than ltBRAF.