Treatment of acute promyelocytic leukaemia

Currently available clinical results show that the combination of ATRA and anthracycline-Ara-C chemotherapy can slightly increase the CR rate in newly diagnosed APL, from about 80% (with chemotherapy alone) to more than 90%, and patients presenting with high leukocyte counts seem to benefit particularly from this combined therapy. ATRA followed by chemotherapy also reduces the incidence of relapse (particularly of early relapse) as compared to chemotherapy alone. However, treatment with ATRA is still complicated by the risk of hyperleukocytosis and potentially fatal ATRA syndrome, whose best preventive approach (addition of chemotherapy and/or dexamethasone) is still debated. Because some patients still relapse after ATRA plus chemotherapy, prognostic factors for relapse need to be precisely determined. They certainly include persistence or re-appearance of PML-RAR transcript during follow-up. Allogeneic BMT should be considered in those patients. Most of the patients who are not cured by the combination of ATRA and chemotherapy or by subsequent allogeneic BMT still die from their disease. This is due to the acquisition by APL cells of progressive resistance to ATRA, that appears to depend on induction of increased ATRA catabolism in APL cells. Current efforts aimed at overcoming this resistance (including intermittent ATRA schedules, synthesis of new retinoid compounds, utilization of inhibitors of cytochrome P450) are being developed.