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.

Objectives: A lot of medication risks related to high-dose methotrexate (HDMTX) therapy still remain to be identified and standardized. This study aims to establish an evidence-based practice guideline for individualized medication of HDMTX. Methods: The practice guideline was launched by the Division of Therapeutic Drug Monitoring, Chinese Pharmacological Society. The guideline was developed following the WHO handbook for guideline development and the methodology of evidence-based medicine (EBM). The guideline was initially registered in the International Practice Guidelines Registry Platform (IPGRP-2017CN021). Systematic reviews were conducted to synthesis available evidence. A multicenter cross-sectional study was conducted by questionnaires to evaluate patients’ perception and willingness on individualized medication of HDMTX. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to rate the quality of evidence and to grade the strength of recommendations. Results: Multidisciplinary working groups were included in this guideline, including clinicians, pharmacists, methodologists, pharmacologists and pharmacoeconomic specialists. A total of 124 patients were involved to integrate patient values and preferences. Finally, the guideline presents 28 recommendations, regarding evaluation prior to medication (renal function, liver function, pleural effusion, comedications, genetic testing), pre-treatment and routine dosing regimen, therapeutic drug monitoring (necessity, method, timing, target concentration), leucovorin rescue (initial timing, dosage regimen and optimization), management of toxicities. Of them, 12 are strong recommendations. Conclusions: We developed an evidence-based practice guideline with respect to HDMTX medication using a rigorous and multidisciplinary approach. This guideline provides comprehensive and practical recommendations involving the whole process of HDMTX medication to health care providers.

Background Langerhans cell histiocytosis (LCH) is a rare disease with a high frequency of the BRAFV600E mutation. We sought to investigate the effectiveness and safety of Dabrafenib in children with BRAFV600E-mutated LCH. Procedure A retrospective analysis was performed on 20 children with BRAFV600E -mutated LCH, who were treated with Dabrafenib and followed up from November 1, 2016, to June 1, 2020. Results The median age at which the patients started taking Dabrafenib was 2.3 (0.6-6.5) years old . All patients were initially treated with chemotherapy and then changed to targeted therapy due to poor response or intolerance to chemotherapy. The overall objective response rate and disease control rate were 65% and 75%, respectively. Among the 15 patients who had positive circulating cell-free BRAFV600E (cfBRAFV600E) mutation before Dabrafenib treatment, decreased cfBRAFV600E level was observed at the end of treatment (P=0.029). In 9 of 15 (60%) patients, cfBRAFV600E level became negative within a median time of 3.0 months (1.0-9.0 months). All patients survived, and a half of them suffered a relapse or progression after Dabrafenib treatment. Grade 2 or 3 adverse effects occurred in 5 patients. Relief of adverse effects was obtained after symptomatic treatment, reduction of dosage or withdrawal. Conclusions Some children with BRAFV600E-mutated LCH may benifit from monotherapy of Dabrafenib, especially high-risk patients with concomitant HLH and intolerance to chemotherapy. The safety of Dabrafenib is notable. A prospective study with a larger sample size are required to determine the optimal dosage and duration of Dabrafenib.