Pediatric health, medicine and therapeutics · 2026
Early Prediction Model for Etoposide-Based Protocols Resistance in Pediatric HLH.
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Wu Jiajia, Xie Longlong, Li Xun, Yan Haipeng, Yang Yufan, Luo Ting, Wang Xiangyu, Zhang Xinping, Huang Jiaotian, Zheng Mincui, Yang Haixia, Lu Xiulan
Аннотация
BACKGROUND: Etoposide-based protocols remain the first-line therapy for pediatric hemophagocytic lymphohistiocytosis (HLH), yet 20-30% of patients exhibit primary resistance. Early identification of non-responders is critical to enable timely salvage therapy. We aimed to develop and validate a predictive model for etoposide-based protocols resistance using readily available clinical and laboratory parameters.
METHODS: A retrospective cohort of 79 pediatric HLH patients (median age 3.5 years; 53% male) treated with etoposide-based protocols (HLH-94/2004) at Hunan Children's Hospital (2020-2024) was analyzed. Patients were stratified into refractory (n=20) and responsive (n=59) groups based on 8-week treatment outcomes. Chemosensitive patients were defined as those achieving complete response (CR) or entering maintenance by week 8; chemorefractory patients were defined as those who died during induction, required salvage therapy due to progression, or failed to achieve CR within 8 weeks. CR required normalization of all quantifiable disease markers (sCD25, ferritin, triglycerides, ALT, hemoglobin, neutrophils, platelets). Pre-chemotherapy and early post-chemotherapy (Day 3) variables were compared using t-tests, Mann-Whitney U-tests, and χ2 analyses. Multivariable logistic regression and ROC analyses identified predictors of resistance, with internal validation via 1000-bootstrapping.
RESULTS: Pre-chemotherapy IL-10 >131.2 μmol/L (OR=5.1; 95% CI 1.9-13.7; P=0.001) and pre-chemotherapy platelet count <55.5×109/L (OR=4.2; 95% CI 1.6-11.3; P=0.004) independently predicted refractoriness. A combined model incorporating these parameters achieved an AUC of 0.822 (sensitivity 81.3%, specificity 75.0%). Post-chemotherapy Day 3 platelet count (OR=1.02 per 109/L increase; P=0.01) and lymphocyte count (OR=2.5 per 109/L increase; P=0.03) further refined prediction (AUC 0.880). Calibration curves and decision curve analysis confirmed clinical utility.
CONCLUSION: Pre-chemotherapy IL-10 and platelet count reliably identify pediatric HLH patients at high risk of etoposide-based protocols resistance. Integration of Day 3 post-chemotherapy parameters enables ultra-early and more precise risk stratification, facilitating prompt transition to salvage therapies.
METHODS: A retrospective cohort of 79 pediatric HLH patients (median age 3.5 years; 53% male) treated with etoposide-based protocols (HLH-94/2004) at Hunan Children's Hospital (2020-2024) was analyzed. Patients were stratified into refractory (n=20) and responsive (n=59) groups based on 8-week treatment outcomes. Chemosensitive patients were defined as those achieving complete response (CR) or entering maintenance by week 8; chemorefractory patients were defined as those who died during induction, required salvage therapy due to progression, or failed to achieve CR within 8 weeks. CR required normalization of all quantifiable disease markers (sCD25, ferritin, triglycerides, ALT, hemoglobin, neutrophils, platelets). Pre-chemotherapy and early post-chemotherapy (Day 3) variables were compared using t-tests, Mann-Whitney U-tests, and χ2 analyses. Multivariable logistic regression and ROC analyses identified predictors of resistance, with internal validation via 1000-bootstrapping.
RESULTS: Pre-chemotherapy IL-10 >131.2 μmol/L (OR=5.1; 95% CI 1.9-13.7; P=0.001) and pre-chemotherapy platelet count <55.5×109/L (OR=4.2; 95% CI 1.6-11.3; P=0.004) independently predicted refractoriness. A combined model incorporating these parameters achieved an AUC of 0.822 (sensitivity 81.3%, specificity 75.0%). Post-chemotherapy Day 3 platelet count (OR=1.02 per 109/L increase; P=0.01) and lymphocyte count (OR=2.5 per 109/L increase; P=0.03) further refined prediction (AUC 0.880). Calibration curves and decision curve analysis confirmed clinical utility.
CONCLUSION: Pre-chemotherapy IL-10 and platelet count reliably identify pediatric HLH patients at high risk of etoposide-based protocols resistance. Integration of Day 3 post-chemotherapy parameters enables ultra-early and more precise risk stratification, facilitating prompt transition to salvage therapies.