Novel Treatment Approaches

Investigators from Shanghai52 53 have recently reported results in 61 newly diagnosed APL patients who received induction therapy with combined ATRA (25 mg/m2/day) plus arsenic trioxide (0.16 mg/kg/day). All patients subsequently received three courses of consolidation chemotherapy, and five cycles of maintenance with sequential ATRA, arsenic, and 6-MP and MTX. Among the 61 patients, 58 (95.1%) entered CR at a median of 26 days and, with a follow up of 20-39 months, all of them were relapse free.52 Similar results, at least for induction, have been reported by Wang et al.,54 with a CR rate in 80 newly diagnosed patients treated with low-dose ATRA plus arsenic of 92.5%; there were two early deaths (2.5%), and four cases of resistant leukemia, but no data were presented on long-term outcomes. Estey et al.34 have treated 44 newly diagnosed APL patients with ATRA (45 mg/m2/ day) plus arsenic trioxide (0.15 mg/kg/day) added at day 10 (with addition of one dose of gemtuzumab ozogamicin if the presenting WBC count was above 10,000/^L or if disease persistence was documented by RT-PCR); treatment with ATRA/arsenic trioxide was continued for 6 months from CR. The rate of CR was 89%, there were four early deaths (9.14%), and 36 of 39 patients were alive in CR at early follow up. Finally, investigators from Iran55 and India56 have separately reported results with arsenic trioxide alone as the sole treatment of APL. Rates of CR, were 85.6 and 86% respectively, for the two studies and, relapse rates were approximately 25%.56 56 In patients with a WBC count lower than 5000 ^L, and a platelet count higher than 20,000 ^L at dignosis, the EFS was 100%.

Studies such as these must be viewed in context of the data summarized in Table 6.1, particularly the more recent trials. While results with arsenic trioxide alone and ATRA plus arsenic trioxide are encouraging, the number of patients treated to date is relatively small, follow up is short, and extensive experience with these agents is limited to selected centers and countries. In addition, the toxicities of arsenic trioxide and ATRA are not trivial, and there is, as yet, no standardized strategy for postremission therapy in patients who receive this type of induction. Despite these caveats, treatment with arsenic trioxide alone, or arsenic trioxide combined with ATRA, may well be suitable for selected patients with low-risk APL, or for patients who are not candidates for, or who refuse, cytotoxic chemotherapy.

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