Arsenic Containing Triple-Agent Therapy for Acute Promyelocytic Leukemia-Comparison of Tetra-Arsenic Tetra-Sulfide vs. Arsenic Trioxide in the Long-Term Follow-up at a Single Hospital.

Abstract 1081

Our previous study has demonstrated that oral tetra-arsenic tetra-sulfide (As₄S₄) alone is highly effective and safe in both induction and maintenance therapy in acute promyelocytic leukemia (APL) (Dao-Pei Lu et al., Blood 2002; 99: 3136). Triple-agent treatment with As₄S₄, all-trans retinoid acid (ATRA) and low-dose chemotherapy has achieved expeditiously consecutive complete remission (CR) without death during induction, and it has also improved leukemia-free survival (LFS) (Tong Wu et al., ASH abstract 591 2007). To learn the efficacy and safety of As₄S₄ and arsenic trioxide (ATO), a total of 88 consecutive cases of newly diagnosed APL patients who have been treated with triple-agent regimen with arsenic, either As₄S₄ (n=42) or ATO (n=46), ATRA and low-dose chemotherapy at Beijing Dao-Pei Hospital were analyzed retrospectively. Major clinical characteristics in two groups were similar. Purified natural oral As₄S₄ (Dao-Pei Lu's Lab) or commercially available intravenous ATO were used. The regimens for induction, consolidation and maintenance therapy have been reported previously. All 88 patients attained hematological CR (HCR) after induction therapy without early death. A total of 84 cases were monitored for PML/RARA fusion transcript by RQ-PCR. Molecular CR (MCR) reached in all evaluable cases (100%) in As₄S₄ group and 93.5% of cases in ATO group. In As₄S₄ group, 3-year and 5-year LFS rates were all 100% with a median follow-up of 57 months (range, 12–103 months). In ATO group, however, 5 cases relapsed and 2 patients died with a median follow-up of 36 months (range, 12–96 months). The 3-year and 5-year LFS rates were both 86.6%. The difference of LFS between As₄S₄ and ATO groups were remarkable (p=0.028). Three-year and 5-year overall survival (OS) rates were all 100% in As₄S₄ group, 96.7% and 88.6% in ATO group respectively. Statistically there was no significant difference (p=0.1015). The side effects in As₄S₄ group were mild and all patients could continue the therapy. However, a total of 15 side events in ATO group including hepatic, cardiac or lung complications led to discontinuation of therapy. Our encouraging clinical results indicate that arsenic, either As₄S₄ or ATO in combination with ATRA and low-dose chemotherapy is highly effective in the induction of both HCR and MCR in newly diagnosed APL patients. As₄S₄ containing triple-agent protocol has better results in the prevention of relapse and improvement of LFS, and has less toxicity. Our clinical study has shown for the first time that all consecutive newly diagnosed cases of APL have achieved long-term LFS with As₄S₄ containing triple-agent regimen, which are significantly better than that of ATO containing one.