Acute Differentiation Syndrome

Differentiation syndrome (DS) is a life-threatening complication of treatment with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) for acute promyelocytic leukemia. Symptoms typically include fever, weight gain, dyspnea, and hypoxia with pulmonary infiltrates or pleural or pericardial effusions identified on chest imaging. Management involves immediate corticosteroid administration; discontinuation of ATRA/ATO and initiation of cytoreductive agents may be necessary in severe cases. Prophylaxis with steroids is traditionally indicated for those with WBC >10 k. DS has also been observed with targeted agents, most notably IDH1/2 and FLT3 inhibitors. The clinical features are similar, though the onset is more insidious, occurring weeks to months following therapy initiation. Management involves corticosteroids and often does not preclude future use of the offending agent. Here, we detail two cases of ATRA and TKI-mediated DS, offering recommendations for diagnosis and management.