Newly Diagnosed Acute Promyelocytic Leukemia: Arsenic Moves Front and Center

Abstract

Treatment of acute promyelocytic leukemia (APL) with alltrans retinoic acid (ATRA), anthracyclines, and increasingly, cytarabine (ara-C) is often prohibitively expensive in the developing world. This encouraged Ghavamzadeh et al 1 in Iran to treat newly diagnosed APL without these standard drugs and rather to rely on arsenic trioxide (ATO), a drug with well-known activity in relapsed APL. 2 As reported in the article that accompanies this editorial, Ghavamzadeh et al observed a complete remission (CR) rate of 86% in 197 patients. Typical of APL, failure to enter CR resulted essentially exclusively from death, most often resulting from hemorrhage before CR could occur (“early death”). As is usual, early death was more frequent (42%v 6%) in patients with a WBC count greater than 10,000/L (hereafter high risk). Patients in CR continued receiving ATO, initially only for one 4-week course, but later, patients were given four such courses. With a median follow-up of 38 months of patients entering CR, 5-year disease-free survival (DFS) probability is 67% 4%, and 5-year overall survival (OS) probability is 64% 4% ( standard deviation). These rates will likely remain stable given that only one relapse was seen among 36 patients who were observed for more than 5 years. Patients given more than one consolidation course had a 5-year DFS of approximately 90% compared with the 5-year DFS of approximately 60% in patients given only one consolidation course; this observation appears somewhat self-fulfilling, given that patients had to remain in CR for more than 1 year to receive the third consolidation course and more than 2 years to receive the fourth. Recently, Mathews et al 3,4 in India administered ATO 10 mg daily until CR in 72 patients with newly diagnosed disease; 24% of these patients had a WBC count greater than 10,000/L, and most could not afford standard therapy. Eleven percent received one to two doses of an anthracycline during induction, but once in CR, patients received only ATO 10 mg each day for one month and then 10 days per month for 6 months. The CR rate was 86%; with a median follow-up of 5 years, DFS and OS probabilities were 80% 5% and 74% 5%, respectively. 4