Extramedullary relapse after all-trans retinoic acid treatment in acute promyelocytic leukemia - the occurrence of retinoic acid syndrome is a risk factor

All-trans retinoic acid (ATRA) is now a standard agent for remission induct ion of acute promyelocytic leukemia (APL). Recently, extramedullary relapse , which was a rare condition in APL patients after chemotherapy alone, was reported with an increased frequency after ATRA treatment. However, it is n ot yet clear whether ATRA truly increases the risk of extramedullary recurr ence and what are the risk factors. In this study, three of 13 patients wit h recurrent APL after prior treatment of ATRA were found to have extramedul lary involvement, compared with none in 11 recurrent patients previously tr eated with chemotherapy alone (estimated relative risk 2.100, 95% confidenc e interval 1.341-3.289). Furthermore, in the former group of patients, the development of retinoic acid (RA) syndrome during prior induction treatment was significantly associated with extramedullary involvement at relapse (t hree in five patients with RA syndrome vs none in eight without the syndrom e, estimated relative risk 5.000, 95% confidence interval 1.448-17.271). In conclusion, ATRA may predispose APL patients to extramedullary involvement at relapse and the occurrence of RA syndrome is a risk factor for it. Furt her studies are needed to confirm these findings. It also remains to be cla rified whether treatment modification is necessary in patients who develop RA syndrome during ATRA treatment.