Rare but important adverse effects of all-trans retinoic acid in acute promyelocytic leukemia and their management.

Several adverse effects have been reported to occur after clinical application of all-trans retinoic acid (RA) in acute promyelocytic leukemia (APL). Except for severe side effects including retinoic acid syndrome, the mechanism of action of RA on adverse effects remains unclear. Here we describe some rare adverse effects and their management. We reviewed the English literature, and we added our cases of endocrine and metabolic adverse effects, such as hypercalcemia, male infertility, bone marrow necrosis, fibrosis and acute pancreatitis. We also described our cases of thromboembolic events, RA-dependent growth of pathologic cells including Sweet's syndrome, erythema nodosum, hyperhistaminemia, granulomatous proliferation, and mild cases of pulmonary complications. In addition, we reviewed the efficacy of RA administration for other types of leukemia or myelodysplastic syndrome. RA and chemotherapeutic agents might induce complete remission, but we obtained a response in only one case of M2 in the third relapse. During RA administration the patient should be monitored for these adverse effects, and early diagnosis and appropriate treatment are important.