Differentiation and apoptosis induction therapy in acute promyelocytic leukaemia
Abstract
Induction of differentiation and/or apoptosis is a new and promising approach to cancer therapy, well illustrated by the treatment of acute promyelocytic leukaemia with all-trans-retinoic acid and arsenic compounds. Treatment with all-transretinoic acid results in complete remission in 92 - 95% of patients with this disease. Using the recently advocated combination of all-transretinoic acid and chemotherapy, adverse effects such as retinoic acid syndrome have decreased, and long-term survival has improved. Chemotherapy in combination with all-trans-retinoic acid seems to be the best postremission treatment protocol, with a 5-year relapse-free survival rate of 50 - 60%. Arsenic compounds have recently proved effective in newly diagnosed and relapsed acute promyelocytic leukaemia, with complete remission rates of 80 - 90% according to most reports. As2O3, the most studied arsenic compound, can be given by intravenous infusion at a dose of 0.08 - 0.16 mg/kg daily. A course of 28 - 44 days is required to induce remission. Although the drug is safe in patients who have relapsed, severe liver damage has been observed in some newly diagnosed patients. Combined use of chemotherapy and arsenic as postremission treatment results in longe...Continue Reading
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Apoptosis
Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis