Extramedullary involvement in the absence of bone marrow disease is rare in patients with acute promyelocytic leukemia (APL). We report two patients with APL who had central nervous system (CNS) relapse without evidence of cytologic and molecular disease of bone marrow after all-trans-retinoic acid (ATRA) treatment. Both of the patients were treated successfully with combination of intrathecal chemotherapy and radiotherapy with or without systemic chemotherapy. Although increasing number of cases with extramedullary involvement of APL after ATRA including therapy have been reported, further studies with a large series of patients are necessary to determine whether ATRA increases the risk of development of extramedullary involvement of disease in patients with APL.
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