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

Area of Science:

• Pediatric Hematology
• Oncology
• Immunology

Background:

• Etoposide-based chemotherapy is the standard first-line treatment for pediatric hemophagocytic lymphohistiocytosis (HLH).
• A significant proportion of pediatric HLH patients (20-30%) exhibit primary resistance to etoposide-based protocols.
• Timely identification of non-responsive patients is essential for initiating effective salvage therapies.

Purpose of the Study:

• To develop and validate a predictive model for etoposide resistance in pediatric HLH.
• To utilize readily available clinical and laboratory parameters for early prediction.
• To improve treatment outcomes by enabling prompt salvage therapy.

Main Methods:

• Retrospective analysis of 79 pediatric HLH patients treated with etoposide-based protocols.
• Stratification into refractory (n=20) and responsive (n=59) groups based on 8-week treatment outcomes.
• Multivariable logistic regression and ROC analyses to identify predictors of resistance, with internal validation via bootstrapping.

Main Results:

• Pre-chemotherapy IL-10 >131.2 μmol/L (OR=5.1) and platelet count <55.5×10⁹/L (OR=4.2) independently predicted refractoriness.
• A combined model using these parameters achieved an AUC of 0.822.
• Incorporating Day 3 post-chemotherapy platelet and lymphocyte counts further improved prediction accuracy (AUC 0.880).

Conclusions:

• Pre-chemotherapy IL-10 and platelet counts are reliable indicators of etoposide resistance in pediatric HLH.
• Integrating early post-chemotherapy parameters allows for ultra-early and precise risk stratification.
• This predictive model facilitates timely transition to salvage therapies for non-responsive patients.