Bradycardia during Induction Therapy with All-trans Retinoic Acid in Patients with Acute Promyelocytic Leukemia: Case Report and Literature Review

A 41-year-old man with newly diagnosed acute promyelocytic leukemia (APL) received induction chemotherapy, containing all-trans retinoic acid (ATRA), idarubicin, and arsenic trioxide. On the 11th day of therapy, he experienced complete atrioventricular (AV) block; therefore, ATRA and arsenic trioxide were immediately postponed. His heart rate partially recovered, and ATRA was rechallenged with a half dose. However, complete AV block as well as differentiation syndrome recurred on the next day. ATRA was immediately discontinued, and a temporary pacemaker was inserted. Two days after discontinuing ATRA, AV block gradually improved, and ATRA was uneventfully rechallenged again. The Naranjo adverse drug reaction probability scale was 7 for ATRA, suggesting it was the probable cause of arrhythmia. A literature search identified 6 other cases of bradycardia during ATRA therapy, and all of them occurred during APL induction therapy, with onset ranging from 4 days to 25 days. Therefore, monitoring vital signs and performing electrocardiogram are highly recommended during the first month of induction therapy with ATRA. ATRA should be discontinued if complete AV block occurs. Rechallenging with ATRA can be considered in fully recovered and clinically stable patients.