Incorporation of arsenic trioxide in initial therapy induction and consolidation for acute promyelocytic leukemia reduced the risk of relapse when compared with historical controls, according to a study published online ahead of print in the Lancet Haematology.

Initial treatment of acute promyelocytic leukemia traditionally involves tretinoin combined with anthracycline-based risk-adapted chemotherapy, with arsenic trioxide being the treatment of choice at relapse.

In an attempt to reduce relapse rate, researchers combined arsenic trioxide with tretinoin and idarubicin in induction therapy, and used arsenic trioxide with tretinoin as consolidation therapy.

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A total of 124 patients were enrolled between November 2004 and September 2009 in this non-randomized phase 2 trial. Eligibility included patients with previously untreated genetically confirmed acute promylocytic leukemia, an Eastern Cooperative Oncology Group performance status 0 to 3, age older than 1 year, normal left ventricular ejection fraction, Q-Tc interval less than 500 ms, and absence of serious comorbidity.

Induction therapy was made up of 45 mg/m2 oral tretinoin in four divided doses daily on days 1 to 36, 6 to 12 mg/m2 intravenous idarubicin on days 2, 4, 6, and 8, adjusted for age, and 0.15 mg/kg intravenous arsenic trioxide once daily on days 9 to 36.

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Supportive therapy included blood products for protocol-specified hemostatic targets, and 1 mg/kg prednisone daily as prophylaxis against differentiation syndrome. Two consolidation cycles with tretinoin and arsenic trioxide were followed by maintenance therapy with oral tretinoin, 6-mercaptopurine, and methotrexate for 2 years. 

Four (3%) patients died early. After a median follow-up of 4.2 years, the 5-year freedom from relapse rate was 95% (95% CI: 89-98), disease-free survival was 95% (95% CI: 89-98), event-free survival was 90% (95% CI: 83-94), and overall survival 94% (95% CI: 89-97).


  1. Iland HJ, Collins M, Bradstock K, et al. Use of arsenic trioxide in remission induction and consolidation therapy for acute promyelocytic leukaemia in the Australasian Leukaemia and Lymphoma Group (ALLG) APML4 study: a non-randomised phase 2 trial. Lancet Haematol. 2015. [epub ahead of print]. doi: 10.1016/S2352-3026(15)00115-5.