DISCUSSION: Differentiation syndrome (DS) occurs in up to 25% of patients during induction treatment with ATRA. Factors associated with developing DS include elevated white blood cell count at diagnosis and increased body mass index. Clinical symptoms occur in a bimodal pattern - 48% within 1 week and 38% in 3-4 weeks after starting ATRA. In APL, myeloid differentiation is halted at the promyelocytic stage due to an aberrant protein, PML/RARa, encoded by the fusion of promyelocytic gene and retinoic acid receptor alpha gene, which binds deoxyribonucleic acid and halts transcription and differentiation. Treatment with ATRA dissociates the PML/RARa protein from its binding site and promotes the differentiation of promyelocytes into neutrophils, basophils and eosinophils. The rapid differentiation leads to migration of neutrophils into the lung, causing a cytokine storm and diffuse capillary leak. Glucocorticoids are the mainstay of therapy. Most patients experience rapid improvement within 24-48 hours. Without glucocorticoids, mortality can be as high as 30%.