Bone marrow necrosis in two patients with acute promyelocytic leukemia during treatment with all-trans retinoic acid.

All-trans retinoic acid has been used for the treatment of acute promyelocytic leukemia (APL) with encouraging results. However, it has recently been associated with a number of potentially serious complications including the retinoic acid syndrome. We describe two patients with APL who were begun on all-trans retinoic acid therapy (45 mg/m2), but who developed leukocytosis which was treated with hydroxyurea. Both patients demonstrated clinical and laboratory findings of disseminated intravascular coagulation, massive cell lysis manifested by marked increases in serum lactic dehydrogenase, and rapid clinical deterioration. Both patients developed bone marrow necrosis within viable, noninfarcted bone trabeculae. We postulate that the development of bone marrow 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 massive cell lysis and death. The absence of bone marrow necrosis in the setting of induction therapy for APL both with and without all-trans retinoic acid therapy suggests that the addition of hydroxyurea was critical to the development of marrow necrosis. We, therefore, recommend caution in the use of hydroxyurea and all-trans retinoic acid in the treatment of APL.