Background: Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm with inflammatory characteristics. This study aims to investigate the correlation between sCD25 levels and clinical characteristics and prognosis in pediatric LCH. Procedure: Serum sCD25 levels were measured in 370 LCH patients under 18 years old using ELISA assays. The patients were divided into two cohorts based on different treatment regiments. We further assessed the predictive value for prognosis impact of sCD25 in a test cohort, which was validated in the independent validation cohort. Results: The median serum sCD25 level at diagnosis was 3908 pg/ml (range: 231-44 000). sCD25 level was significantly higher in MS RO+ LCH patients compared to SS LCH patients ( P<0.001). Patients with increased sCD25 were more likely have involvement of risk organs, skin, lung, lymph node, or pituitary (all P < 0.05). sCD25 level could predict LCH progression and relapse with an area under the ROC curve of 60.6%. The best cutoff value was determined at 2921 pg/ml. High-sCD25 group had a significantly worse progression-free survival than those in the low-sCD25 group ( P < 0.05). Conclusion: Elevated serum sCD25 levels at initial diagnosis was associated with high-risk clinical features and worse prognosis. sCD25 levels can predict the progression/recurrence of LCH after treatment with first-line chemotherapy.

Langerhans cell histiocytosis (LCH) is a rare hematologic neoplasm characterized by the clonal proliferation of Langerhans-like cells. Colony-stimulating Factor 1 receptor (CSF1R) is a membrane-bound receptor that is highly expressed in LCH cells and tumor-associated macrophages. In this study, a soluble form of CSF1R protein (sCSF1R) was identified by plasma proteome profiling, and its role in evaluating LCH prognosis was explored. We prospectively measured plasma sCSF1R levels in 104 LCH patients and 10 healthy children using ELISA. Plasma sCSF1R levels were greater in LCH patients than in healthy controls ( P < 0.001) and significantly differed among the three disease extents, with the highest level in MS RO+ LCH patients ( P < 0.001). Accordingly, immunofluorescence showed the highest level of membrane-bound CSF1R in MS RO+ patients. Furthermore, the plasma sCSF1R concentration at diagnosis could efficiently predict the prognosis of LCH patients treated with standard first-line treatment (AUC =0.782, P < 0.001). Notably, dynamic monitoring of sCSF1R levels could predict relapse early in patients receiving BRAF inhibitor treatment. In vitro drug sensitivity data showed that sCSF1R increased resistance to Ara-C in THP-1 cells expressing ectopic BRAF-V600E. Overall, the plasma sCSF1R level at diagnosis and during follow-up is of great clinical importance in pediatric LCH patients.

Objective To investigate the clinical characteristics, treatment, and prognosis of children with systemic juvenile xanthogranuloma (JXG). Methods Children with JXG from January 2012 to December 2019 were retrospectively analyzed. Data relating to the clinical manifestations, laboratory values, treatment, and prognosis of the children were extracted from medical records. Patients underwent vindesine +prednisone as the first-line treatment and cytarabine + vindesine + dexamethasone +/- cladribine as the second-line treatment. Results Ten patients, including 8 males and 2 females, with an onset age of 1.95 (0.80-7.30) years, exhibited multi-system dysfunction. The median age of diagnosis was 2.45 (1.30-12.10) years. The most common location of extracutaneous lesions was the central nervous system (6 cases), followed by the lung (5 cases) and bone (4 cases). Nine patients underwent first-line chemotherapy, and 6 patients underwent second-line chemotherapy, including 5 patients with poorly controlled disease after first-line treatment. The median observation time was 20 (3-106) months. Nine patients survived, whereas one patient died of respiratory failure caused by pulmonary infection. By the end of follow-up, 7 patients were in an active disease (AD) state but better (AD-better), and 2 patients were in an AD-stable state. Three patients had permanent sequelae, mainly, central diabetes insipidus. The first-line treatment response rate was 40.0%, and the second-line treatment response rate was 66.7%. Conclusion The chemotherapy protocol for Langerhans cell histiocytosis (LCH) was effective for patients with systemic JXG, which also resulted in good outcomes. Central nervous system involvement did not impact overall survival, but serious permanent sequelae remained.