Induction treatment of acute promyelocytic leukemia using all-trans retinoic acid. Controversies about dosage, advantages and side-effect management

All-trans retinoic acid (ATRA) in acute promyelocytic leukemia (APL) represents the leading example of targetted drugs for inducing an in vivo differentiation of malignancy (1,2). A fixed dose of 45 mg/m2/day was proposed for the treatment of patients (3), according to the results obtained by retinoic acid derivatives in skin diseases. We report that 25 mg (4), and even 15 mg/m2/day are still effective dosages. Absence of drug resistance, rapid correction of fibrinogenopenia and the absence of hypoplasia are the apparent major advantages and consequently high frequency of early mortality generally reported during chemotherapy is expected to be reduced. In fact the same risk of early death (10%) is recorded in all available data (5), due to coagulation disorders and to a leukocyte activation syndrome. Management of these side-effects is based on the prevention and treatment of the irreversible state as soon as first symptoms appear. Actually the major advantage of ATRA treatment in addition to chemotherapy is the decrease of relapse rate (6), the increase of event-free survival, and thus the increase of survival.