Efficacy of Etoposide-Based Therapy in Pediatric Secondary Hemophagocytic Lymphohistiocytosis.
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OBJECTIVES: Secondary hemophagocytic lymphohistiocytosis (sHLH) is a severe hyperinflammatory syndrome requiring rapid recognition and treatment. Despite the expanding availability of biologic and cytokine-directed therapies, etoposide-based immunochemotherapy remains the primary treatment in many pediatric centers. This study evaluated the efficacy, response kinetics, and clinical outcomes of etoposide-based therapy in children with sHLH. METHODS: We retrospectively analyzed 32 pediatric patients diagnosed with sHLH between 2018 and 2023 at a tertiary center. Diagnosis was based on HLH-2004 criteria; primary HLH was excluded through genetic testing when available. All patients received dexamethasone and etoposide, with cyclosporine A initiated after Week 1. Trigger-directed therapies included rituximab for EBV-HLH and anakinra or tocilizumab in selected hyperinflammatory states. Laboratory dynamics (ferritin, fibrinogen, platelets, and absolute neutrophil count), clinical responses, relapse, hematopoietic stem cell transplantation (HSCT), and overall survival (OS) were assessed. RESULTS: The median age was 38 months; 62.5% were male. Triggers included EBV (34%), other viral infections (19%), rheumatologic disease/MAS (16%), bacterial infection (13%), and malignancy (9%). By Week 4, ferritin decreased from 6480 to 1240 ng/mL and fibrinogen increased from 122 to 286 mg/dL (p < 0.001). Fever resolved in 90% by Week 2, and 81% achieved complete laboratory response. During a median follow-up of 18 months, relapse occurred in 18.8% and HSCT was required in 15.6% of patients. Overall survival was 91% at 1 year and 86% at 2 years. Adverse events were consistent with expected etoposide-related toxicities. CONCLUSION: Etoposide-based immunochemotherapy provided rapid disease control and favorable survival in pediatric sHLH. These findings support the continued relevance of etoposide while underscoring the need for risk-adapted approaches integrating trigger-directed therapy, cytokine inhibitors, and timely HSCT in selected patients.