Single Agent Arsenic Trioxide in the Treatment of Newly Diagnosed Acute Promyelocytic Leukemia: Long Term Follow-up Data.

Abstract 846

We had previously reported a well tolerated regimen using single agent arsenic trioxide (ATO) (Blood 2006:107; 2627) leading to durable remissions in patients with newly diagnosed acute promyelocytic leukemia (APL). Briefly, the regimen consisted of ATO (10mg/day for adults and 0.15mg/kg/day for pediatric patients) for up to 60 days in induction; this was followed by a 28 day consolidation after a 4 week break. Four weeks after completion of consolidation, patients received ATO for 10 days/month for 6 months. A concern with the previous report was the relatively short duration of follow up.

Here we report the long term follow-up data of the same cohort. As previously reported, 72 newly diagnosed cases of APL were enrolled. 62 patients (86.1%) achieved hematological remission. The remaining died prior to achieving remission. There were no primary induction failures. Twenty two (30.6%) of these patients were considered good risk group (WBC count at diagnosis <5×10⁹/L and a platelet count >20×10⁹/L), the rest were considered high risk. Since publication of the last report an additional 7 patients have relapsed to give a total of 13 relapses, 2 were in the good risk group and the remaining 11 in the high risk group. The relapses in the good risk group were salvaged with an autologous SCT and have durable continued second remissions. The median time to relapse was 1.5 years. Five (38.52%) of these relapses occurred beyond 2 years and included both relapses in the good risk group. At a median follow-up of 58 months the 5-year Kaplan-Meier overall survival (OS), event free survival (EFS) and disease free survival (DFS) of the entire cohort was 74.22±5.26%, 68.93±5.52% and 80.00±5.17% respectively. The 5-year OS and EFS of the good risk and high risk group was 100±00% vs. 63.30±6.9% and 90.00±6.71% vs. 59.66±6.99% respectively. Beyond induction, all deaths followed relapse of disease. There were no second malignancies reported. Besides the previously reported toxicities, which were mild and transient in most cases, there were no new toxicities that were reported on continued follow up of these cases. Since completion of therapy, in spite of counseling and advising against pregnancy, 3 males and 4 females in the reproductive age group have had 8 normal children. No abortions, still births or fetal defects were reported among patients in the reproductive age group in this cohort. Hair and nail samples from 5 cases that had completed maintenance therapy more than 24 months earlier have been collected for analysis, the results of which are awaited. At our center the cost of administering this regimen is a quarter of that of a conventional ATRA plus anthracycline based regimen. Additionally, after the initial induction therapy the rest of the treatment did not require hospital admission nor did it result in any Grade III/IV hematological toxicity.

Single agent ATO based regimen as reported previously is well tolerated, results in durable remissions and does not have any significant late side effects. In the good risk group it is associated with excellent clinical outcomes while in the high risk group additional interventions are probably required to reduce the risk of late relapses. In a resource constrained environment it is probably the best option.