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.

Severe aplastic anemia (SAA) is caused by immune-mediated destruction. Standard immunosuppressive therapy (IST) is effective, but needs to be improved. A total of 115 patients (60 males; median age of 5.77 years and median follow-up time of 45 months) were enrolled in this historical control study. The complete response (CR) rates in the eltrombopag group were 30.3% at 3 months, 50.0% at 6 months, conpared to 8.2% at 3 months, 10.2% at 6 months in the control group. There were significant differences between the two groups at 3 months and 6 months after IST. The overall response rates in the two groups showed no significant differences during the study. There were significant differences in the times separated from granulocyte colony stimulating factor (G-CSF) G-CSF, red blood cell transfusion and Platelet transfusion between the two groups. Overall survival rates were 97.0% in the eltrombopag group and 96.0% in the control group (P=0.998). In the eltrombopag group 10.2% cases relapsed compared to 4.1% in the control group (P=0.703). No case progressed to myelodysplastic syndrome or myeloid leukemia in the eltrombopag group; one patient (2.0%) progressed to myelodysplastic syndrome in the control group. Totally 11 patients (16.7%) showed myeloid gene mutations in the eltrombopag group. Event-free survival (EFS) was 66.6% in the eltrombopag group and 57.1% in the control group. There were no significant differences in EFS between the two groups (P=0.967). In the eltrombopag group the common adverse reactions were transient and reversible hyperbilirubinemia, elevated liver enzymesand hyperuricemia.

In this study, we reported a patient who presents with multicentric reticulohistiocytosis (MRH)-like clinical feature, but the histology is not compatible with it. Like our patient, a couple of patients described previously also had the dilemma that they could not be classified appropriately into any current histiocytosis entity. Considering the clinical and pathological features together, all these patients had a similar clinical profile: xanthomatous rash, erosive arthritis and histopathological findings showing xanthomized histiocytes. Therefore, we propose a new disease entity - xanthomatous erosive arthritis (XEA), to accommodate these patients that cannot be classified appropriately into the current system.

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.

Background: Eltrombopag (E-PAG) is being investigated for the treatment of aplastic anemia (AA) by stimulating hematopoietic stem cell (HSC) proliferation. Objective: To evaluate the effectiveness and safety of E-PAG in first-line therapy for pediatric AA. Methods: The present retrospective study reviewed the pediatric patients with newly diagnosed AA in immunosuppressive therapy (IST) therapy with E-PAG at the single center from March to September in 2017. All patients were followed up for >2 years. Results: A total of 14 patients (8 males), aged 86 months, were enrolled in this study. E-PAG was administered with a median time to initiation of 19.5 days after IST, and the median course of treatment was 253 days. The rate of complete response and overall response at 6 months were 64.3% (9/14 case) and 78.6% (11/14 cases) respectively. The survival rate was 100%, and no relapses occurred in responders. E-PAG was well-tolerated; however, the most common adverse events included indirect bilirubin elevation, jaundice, and transient liver-enzyme elevation. By the end of follow-up, bone marrow chromosomes were normal, and no abnormal myelodysplastic syndromes (MDS) -related clones appeared. Conclusions: The addition of E-PAG to IST was associated with the markedly increased complete response with respect to hematology in pediatric patients with SAA than in a historical cohort without the unacceptable side effects.