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 app lication of all-trans retinoic acid (RA) in acute promyelocytic leukem ia (APL). Except for severe side effects including retinoic acid syndr ome, the mechanism of action of RA on adverse effects remains unclear. Here we describe some ran adverse effects and their management. We re viewed the English literature, and we added our cases of endocrine and metabolic adverse effects, such as hypercalcemia, male infertility, b one marrow necrosis, fibrosis and acute pancreatitis. We also describe d our cases of thromboembolic events, RA-dependent growth of pathologi c cells including Sweet's syndrome, erythema nodosum, hyperhistaminemi a, granulomatous proliferation, and mild cases of pulmonary complicati ons. In addition, we reviewed the efficacy of RA administration for ot her types of leukemia or myelodysplastic syndrome. RA and chemotherape utic agents might induce complete remission, but we obtained a respons e in only one case of M2 in the third relapse. During RA administratio n the patient should be monitored for these adverse effects, and early diagnosis and appropriate treatment are important. (C) 1997 Elsevier Science Ireland Ltd.