Treatement of New Cases of Acute Promyelocytic Leukemia by Arsenic Trioxide Whitout ATRA +/− Chemotherapy and Long Term Follow up of Patients

Acute promyelocytic leukemia (APL) is a unique type of hematologic malignancies with high cure rate. ATRA and chemotherapy is current standard treatment but Arsenic Trioxide (ATO) is most potent single agent against APL.

Materials and methods: between may 2000 and October 2007 we treated 193 new cases by ATO alone. Patients received 0.15 mg/kg ATO as 2 hours daily i.v infusion till complete remission or 60 days, and then received the same dose as consolidation for 28 days, one months after CR. From 2006, increased ATO consolidation to 4 doses (two 28 days in first year and two 28 days in beginning of second and third years). They received Dexamethasone for treatment of APL differentiation syndrome. Patients followed by sensitive RT-PCR for MRD detection. Median follow up was 28 months (1–88) and 38% of cases followed for more than 3 years and 15% for more than 5 years. For treatment of patients after relapse we used ATO again by the same schedule.

Results: Median age of patients was 29+/−13 years and median WBC count at was 2100+/−23319 at diagnosis and 35% of cases have WBC more than 10000 at first presentation. Remission rate was 82.7%. APL differentiation syndrome happened in 31% of patients during remission induction. we observed, by long term follow up that 67.7% of patients are alive. DFS for 2,3 and 5 years were 80%+/−3, 69%+/−4 and 64%+/−5 respectively. Overall survival of patients for 2,3 and 5 years were 86%+/−2, 79+/− 3 and 66%+/−5 respectively. WBC more than 10000 count at diagnosis was associated with increased mortality during remission induction phase (p value< 0.001) but it has no association with DFS or overall survival. Also we observed that chance of relapse for patients with sustained remission at one, two, three and four years after remission induction were 24.6%,16.7%,5.8% and 3% respectively and chance of survival for these patients were 82.8%,88.9%,95% and 100% respectively. For patients who remained in CR after 3 years of remission induction DFS and OS for more than 4 years after remission induction were 94+/−3% for both. These results means that chance of cure for patients on CR is high. Patients who relapsed after first induction could achieve to CR by ATO alone again but their long term prognosis was not good and 68% of them finally died. One year, two, three and four years survival for this group were 88%+−4,72.6%,57.7% and 27+/−7%

Conclusion: ATO treatment is an alternative treatment for APL with good long term result. Reduction of early mortality needs better referral system to earlier beginning of treatment and also better control o APL differentiation syndrome and bleeding (especially from lung and CNS).Also we suggest that for relapsed cases it is better to add other treatment modalities like ATRA, chemotherapy or BMT to improve long term results.