BONE-MARROW NECROSIS IN 2 PATIENTS WITH ACUTE PROMYELOCYTIC LEUKEMIA DURING TREATMENT WITH ALL-TRANS-RETINOIC ACID

All-trans retinoic acid has been used for the treatment of acute promy elocytic leukemia (APL) with encouraging results. However, it has rece ntly been associated with a number of potentially serious complication s including the retinoic acid syndrome. We describe two patients with Apt. who were begun on all-trans retinoic acid therapy (45 mg/m(2)), b ut who developed leukocytosis which was treated with hydroxyurea. Both patients demonstrated clinical and laboratory findings of disseminate d intravascular coagulation, massive cell lysis manifested by marked i ncreases in serum lactic dehydrogenase, and rapid clinical deteriorati on. Both patients developed bone marrow necrosis within viable, noninf arcted bone trabeculae. We postulate that the development of bone marr ow necrosis in these two patients was not a chance occurrence. Rather, the specific combination of cytotoxic and differentiating agents used in these patients (hydroxyurea with all-trans retinoic acid) caused m assive cell lysis and death. The absence of bone marrow necrosis in th e setting of induction therapy for APL both with and without all-trans retinoic acid therapy suggests that the addition of hydroxyurea was c ritical to the development of marrow necrosis. We, therefore, recommen d caution in the use of hydroxyurea and all-trans retinoic acid in the treatment of APL. (C) 1994 Wiley-Liss, Inc.