Severe Pulmonary Differentiation Syndrome Despite Corticosteroid Prophylaxis in Acute Promyelocytic Leukemia: Clinical Improvement With Pulse Methylprednisolone Therapy and High-Flow Nasal Cannula.

Differentiation syndrome (DS) is a potentially life-threatening complication of differentiation therapy in acute promyelocytic leukemia (APL), particularly with all-trans retinoic acid (ATRA) and arsenic trioxide. We report the case of a 37-year-old woman with newly diagnosed APL who developed severe pulmonary DS 48 hours after ATRA initiation despite dexamethasone prophylaxis. She developed progressive hyperleukocytosis, fluid retention, severe hypoxemia, and diffuse bilateral pulmonary infiltrates, requiring high-flow nasal cannula (HFNC) support with an FiO₂ of up to 80% and a flow rate of 60 L/min, combined with awake prone positioning. The initial PaO₂/FiO₂ ratio was 150, and the respiratory rate-oxygenation (ROX) index was 4, indicating a clinical profile associated with a higher risk of intubation. In the absence of bacterial growth from respiratory samples or a cardiogenic cause, DS was considered the predominant mechanism of respiratory deterioration. After 48 hours of HFNC support, the ROX index increased to 8; however, persistent pulmonary involvement prompted escalation to pulse methylprednisolone therapy at 1 g/day for three days. The patient showed clinical, oxygenation, and radiologic improvement, with an increase in the PaO₂/FiO₂ ratio from 150 to 350, and invasive mechanical ventilation was avoided. This case highlights the importance of early recognition of severe pulmonary DS in APL and suggests that individualized corticosteroid intensification combined with advanced noninvasive respiratory support may be useful in selected high-risk patients.