How we prevent and treat differentiation syndrome in patients with acute promyelocytic leukemia

Differentiation syndrome (DS), formerly known as retinoic acid syndrome, is a relatively common and potentially severe complication seen in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and/or arsenic trioxide. The full-blown syndrome consists of unexplained fever, weight gain, dyspnea with pulmonary infiltrates, pleuropericardial effusion, hypotension, and renal failure. Most measures currently used for management of DS have very little evidence-based support, and therefore, many remain controversial. Despite the lack of evidence supporting DS prophylaxis, several groups have adopted a preventive strategy with corticosteroids, especially for patients with leukocyte levels higher than from 5 to 10 × 10(9)/L. DS diagnosis should be suspected in the presence of any of the above-mentioned signs and symptoms, and preemptive treatment with dexamethasone should be started immediately. Other supportive measures can also be crucial for the correct management of DS, especially in those patients with life-threatening complications. Temporary discontinuation of all-trans retinoic acid or arsenic trioxide is indicated only for patients in very poor clinical condition or with severe renal or pulmonary dysfunction, sometimes requiring admission to the intensive care unit. Recognition of specific biomarkers and a better understanding of DS pathogenesis can be helpful for the development of specific therapies to counteract DS in a timely manner.