Clinical features and outcomes of 17 children with systemic juvenile xanthogranuloma (sJXG) including five complicated with hemophagocytic lymphohistiocytosis (HLH)

Juvenile xanthogranuloma (JXG) is primarily limited to the skin, and systemic JXG (sJXG) is rarely reported. Reports of sJXG patients with hemophagocytic lymphohistiocytosis (HLH) are particularly rare. Herein, we conducted a retrospective study of children diagnosed with sJXG in the Hematology Centre of Beijing Children's Hospital from Jan. 2016 to Dec. 2021. The clinical features, laboratory parameters, treatments and outcomes of 17 sJXG patients were investigated, including five complicated with HLH. All sJXG-HLH patients had intermittent fever, rash, hepatosplenomegaly, cytopenia and high levels of soluble CD25, but interferon-gamma was almost normal. Patients with sJXG-HLH had a younger diagnosis age (P = 0.035) and were more likely to have skin, liver, and spleen involvement than those without HLH (P = 0.029, P = 0.003, P = 0.003, respectively). Corticosteroids and/or ruxolitinib could be used to control the hyperinflammatory status when HLH was diagnosed. The treatment of sJXG varied, including Langerhans cell histiocytosis (LCH)-based chemotherapy and targeted therapy. The overall response rate of sJXG for first-line and second-line chemotherapy was 50.0% (5/10) and 50% (4/8), respectively. Patients with BRAF V600E mutation showed a response to dabrafenib. There was no significant difference in the overall survival and progression-free survival between sJXG patients without and with HLH (P = 0.12 and P = 0.46, respectively). Therefore, LCH-based chemotherapy could serve as an effective treatment for sJXG patients, and dabrafenib, to some extent, showed efficacy in controlling sJXG in patients with BRAF V600E mutation. The prognosis of sJXG-HLH patients seemed to be comparable to patients without HLH.