Advances in differentiation syndrome in acute promyelocytic leukemia: From mechanisms to management

Differentiation syndrome (DS) is a life-threatening complication of all-trans retinoic acid and arsenic trioxide therapy for acute promyelocytic leukemia (APL). This review synthesizes the current understanding of DS pathogenesis, from PML::RARA degradation to cytokine storm, endothelial injury, and multi-organ damage, alongside diagnostic criteria, severity grading, and risk stratification. We describe a graded treatment framework encompassing prophylactic, therapeutic, and refractory-phase strategies, with particular emphasis on special populations, predictive models, and emerging therapies. Integrating mechanistic insights with risk-adapted, stepwise therapeutic strategies is essential to reduce DS-associated morbidity and mortality, thereby further improving outcomes in this highly curable disease.