Differentiation syndrome secondary to all-trans-retinoic acid and arsenic trioxide
C. Stop the ATRA and start steroids
Acute promyelocytic leukemia (APL) is an aggressive acute myeloid leukemia characterized by a balanced reciprocal translocation between chromosomes 15 and 17 resulting in a PML-RARα fusion gene; it is also characterized by coagulopathy with lymphocytic blast cell morphology.1 The mainstay of induction therapy for APL is ATRA with arsenic trioxide, with or without anthracycline-based chemotherapy. All-trans-retinoic acid induction therapy leads to terminal differentiation of the malignant blast cell progenitors.
Differentiation syndrome (DS) is a well-known, life-threatening complication of induction therapy with ATRA and arsenic trioxide. The incidence of DS after starting induction therapy ranges from 2.5% to 31%.2 Luesink et al2 suggest that DS is caused by excessive systemic inflammation from chemokines inducing a life-threatening capillary leak syndrome. It classically presents with unexplained fever, respiratory distress, hemodynamic instability, peripheral edema, acute kidney injury, and pleuropericardial effusions. Our patient demonstrated fever, wheezing with pulmonary infiltrates, and bilateral upper extremity edema. On literature search, we found 3 other documented cases of DS presenting with bilateral serous RD, manifesting with only subretinal fluid and no intraretinal fluid or choroidal effusions.3,4 In 2 of these 3 cases, ATRA was discontinued and steroids were started, leading to resolution of the subretinal fluid. Our case would represent, to our knowledge, the first reported ophthalmic DS with choroidal effusion and serous RD with intraretinal fluid. Treatment of DS typically entails pausing ATRA and starting systemic steroids.3,4 Given this patient’s constellation of systemic symptoms and prior reports of serous RD in the setting of DS, the patient started receiving intravenous dexamethasone (choice C).