Early Prediction Model for Etoposide-Based Protocols Resistance in Pediatric HLH.

Authors

Jiajia Wu, Longlong Xie, Xun Li, Haipeng Yan, Yufan Yang, Ting Luo, Xiangyu Wang, Xinping Zhang, Jiaotian Huang, Mincui Zheng, Haixia Yang, Xiulan Lu

Published in

Pediatric health, medicine and therapeutics. Volume 17. Pages 577441. Epub Jun 24, 2026.

Abstract

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.
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.
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.
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.

PMID:
42371597
Bibliographic data and abstract were imported from PubMed on 29 Jun 2026.

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