Early Identification of Differentiation Syndrome During ATRA and Arsenic Therapy in Pediatric NHR-APL: Insights From...

The combination of all-trans retinoic acid (ATRA) with arsenic trioxide (ATO) has dramatically improved the cure rate of acute promyelocytic leukemia (APL). However, differentiation syndrome (DS) remains a significant cause of early mortality in APL patients. This severe complication typically occurs during induction therapy with ATRA and/or ATO. Early prediction and timely intervention are crucial to reducing DS-related mortality. This study aimed to identify risk factors for DS and develop a predictive model tailored to children with non-high-risk (NHR) APL.

We conducted a multicenter retrospective analysis of 166 pediatric NHR-APL patients treated between 2011 and 2024. Clinical characteristics were compared between DS and non-DS groups. Logistic regression was used to identify independent predictors, and a nomogram was developed based on these variables. The model was evaluated using the area under the curve (AUC) and decision curve analysis (DCA).

Seventeen patients (10.2%) developed DS during induction. Multivariate analysis identified five independent risk factors: female sex, non-chemotherapy group, BCR subtype 3, elevated peripheral promyelocyte proportion (≥ 44%), and platelet count (≥ 20 × 10⁹/L). The predictive nomogram achieved an AUC of 0.89 in the training set and 0.75 in the validation set. DCA demonstrated favorable clinical utility of the model.

We developed and validated the first nomogram for predicting DS in pediatric NHR-APL. This tool enables early risk stratification and may guide clinical decision-making to reduce early mortality.