Sequential Treatment of Arsenic Trioxide Followed by All Trans Retinoic Acid with Anthracyclines has Excellent Long-Term Cure in Acute Promyelocytic Leukemia

Abstract

Acute promyelocytic leukemia (APL) remains the most curable myeloid leukemia made feasible through effective use of two differentiating agents, all trans retinoic acid (ATRA) and arsenic trioxide (ATO) with or without chemotherapy (CT). However, early morbidity and mortality remains a problem. With the objective of reducing early death a strategy of sequential induction ATO followed by consolidation ATRA in combination with CT was adopted by our group. The long-term outcomes of patient of APL treated on this sequential approach at our center was analyzed. In this retrospective analysis of prospectively maintained database consecutive adult patients with APL irrespective of their Sanz risk group were treated using a protocol of ATO (10 mg IV infusion over 3 h daily for 45 days) in the first phase followed by ATRA (45 mg/m2 for 60 days) in combination with Daunorubicin (60 mg/m2 for 3 days × 3 cycles) in second phase. All patients received maintenance ATRA (45 m/m2 for 15 days every 3 months) for a period of 18 months in phase 3. Patients were monitored for cytogenetic and molecular responses after phase 1 and 2. All patients were followed up for toxicity, event free and overall survival. 131 consecutive patients were treated in this study. At a median follow up of 60 months, 84.81% patients are alive with an overall event free survival (EFS) of 77.82%. Sanz low risk patients fared better (85%) versus intermediate and high-risk patients who had a 76% EFS. Proportion of patients alive at last follow up were 100% in Sanz low risk group and 82% in intermediate and high-risk group. The sequential schedule showed excellent tolerance and toxicity profile when treating newly diagnosed APL. The long-term follow-up data shows comparable if not better survival compared with the published real-world data and this has been consistent across all risk group.

How I Treat Acute Promyelocytic Leukemia

“…3C ). 29 Patients on follow-up were evaluated for child-bearing potential after the use of ATO and the pregnancy outcomes were reported. 44 A rare toxicity reported for the first time in literature was avascular necrosis of the femur in a patient on ATRA along with chemotherapy and has been subsequently confirmed by other authors.…”

“…This strategy has helped us reduce the induction mortality from APL syndrome from 40% in our initial series to less than 10%. 27,29 If the PB shows morphological remission with normalization of the three lineages, and the marrow is in remission, induction therapy is stopped at 6 to 8 weeks. Early molecular studies are not advised in APL, as the time to remission is around 1.5 months.…”

“…In the long-term, survival outcomes were comparable to the published real-world data. 29 Case: Patient achieved complete hematological remission after the initial induction of ATRA and daunomycin, which was followed by two consolidation ATO on alternate month. She received 560 mg of ATO as a cumulative dose and was advised follow-up at 3 monthly for the first year.…”