Treatment of Relapsing APL Previously Treated with All-trans Retinoic Acid Using Arsenic Trioxide
Division of Hematology, Department of Internal Medicine, Nippon Medical School
All-trans retinoic acid (ATRA) combined with anthracycline-based chemotherapy and followed by maintenance treatment with intermittent ATRA improved the cure rate in patients with newly diagnosed APL to 70% from 35% in patients treated with chemotherapy alone. Nevertheless, disease will relapse in about 20% of patients who achieve a complete remission. Arsenic trioxide (ATO) is an active drug in refractory/relapsed APL with antileukemic mechanisms of inducing partial differentiation and apoptosis. ATO monotherapy in patients with relapsed APL achieved remission rates of more than 80% with molecular remissions. The reported adverse effects (e.g., APL differentiation syndrome, hyperleukocytosis, prolongation of the QTc interval, and liver dysfunction) are few and manageable. A 74-year-old woman in whom APL complicated with subarachnoid hemorrhage was diagnosed achieved complete remission with ATRA in March 2005. Subsequently, she received postremission therapy as an outpatient. In October 2005, leukemia relapse was noted with a white blood cell count of 11.2×109/L (42% blasts), a platelet count of 16×109/L, and disseminated intravascular coagulation (DIC). ATO was administered at a dose of 0.15 mg/kg/day. The DIC resolved after 12 days. The white blood cell count gradually decreased. On day 41, ATO was discontinued due to neutropenia of less than 0.1×109/L. After 14 days, granulocyte colony-stimulating factor (G-CSF) was administered because of sustained neutropenia. Ten days after G-CSF was started, bone marrow aspiration revealed APL cells. ATO was started again with G-CSF, and bone marrow remission was finally achieved after 20 days. ATO is a powerful and promising treatment for refractory/relapsed APL. Neutropenia has recently been reported as an adverse effect. This is the first case of APL successfully treated with ATO and G-CSF for neutropenia followed by remission.
日医大医会誌 2006; 2(3), 152-156
acute promyelocytic leukemia, arsenic trioxide all-trans retinoic acid, differentiation, granulocyte colony-stimulating factor
Sakae Tanosaki, Department of Internal Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan