Differentiation Syndrome in Acute Leukemia: APL and Beyond

SIMPLE SUMMARY: Differentiation syndrome (DS) is a frequent clinical complication of treatment with all-trans retinoic acid (ATRA) and/or arsenic trioxide (ATO), and is typically characterized by non-infectious related fever, dyspnea, hypotension, weight gain > 5 kg, pleural or pericardial effusions, and acute renal failure. DS was initially observed in patients with acute promyelocytic leukemia (APL) treated with ATRA and ATO but was later recognized with other targeted therapies for acute myeloid leukemia (AML). In this review, we discuss the pathogenesis, clinical manifestations, radiological findings, diagnosis, and treatment of DS in patients with APL treated with ATRA and ATO, as well as discuss DS in patients with AML treated with novel therapeutics. ABSTRACT: Differentiation syndrome (DS) is a frequent and potentially life-threatening clinical syndrome first recognized with the advent of targeted therapeutics for acute promyelocytic leukemia (APL). DS was subsequently observed more broadly with targeted therapeutics for acute myeloid leukemia (AML). DS is typically characterized by fever, dyspnea, hypotension, weight gain, pleural or pericardial effusions, and acute renal failure. The incidence in patients with APL ranges from 2 to 37%, with the wide variation likely attributed to different diagnostic criteria, use of prophylactic treatment, and different treatment regimens. Treatment with corticosteroids +/- cytoreductive therapy should commence as soon as DS is suspected to reduce DS-related morbidity and mortality. The targeted anti-leukemic therapy should be discontinued in patients with severe DS. Here, we discuss the pathogenesis of DS, clinical presentations, diagnostic criteria, management strategies, and implementation of prospective tracking on clinical trials.