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Research in Review

Pediatric APL Outcomes Improved By Arsenic Trioxide Consolidation

Consolidation with arsenic trioxide allows for decreased anthracycline dosing while maintaining survival rates and a low risk of relapse in pediatric patients with acute promyelocytic leukemia (APL), according to a new study published in the Journal of Clinical Oncology (online August 2, 2017; doi:10.1200/JCO.2016.71.6183).

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A previous study helped establish the standard-of-care treatment for pediatric patients with APL. However, this treatment involves high-dose anthracycline, which is associated with an increased risk of cardiac toxicity.

Researchers from the children’s Oncology Group and the National Cancer Institute (NCI) conducted a study to assess the impact of reduced cumulative dosing of anthracycline in pediatric patients with APL. The phase III study enrolled 100 patients with standard-risk or high-risk disease to receive all-trans retinoic acid (25 mg/m2/day) twice daily on days 1 through 30 during induction, as well as on days 1 through 14 during every consolidation and maintenance course.

All patients in the study received idarubicin for induction, two cycles of arsenic trioxide for consolidation, and 6-mercaptopurine and oral methotrexate for maintenance.

Patients with standard-risk APL received two additional cycles of consolidation, which included high-dose cytarabine and idarubicin. Patients with high-risk disease received three additional cycles.

Results of the study showed that survival rates were improved for all patients. Three-year overall survival (OS) was 94% in evaluable patients; OS was 98% in patients with standard-risk APL and 86% in patients with high-risk disease (P = .003).

Event-free survival was 91% in evaluable patients; event-free survival was 95% in patients with standard-risk APL and 83% in patients with high-risk disease (P = .03).

Adverse events observed in the study included fever, neutropenia, and infection, with isolated cases of grades 1-5 QTc prolongation, ventricular arrhythmia, and left ventricular dysfunction.  

Authors of the study concluded that favorable results shown from incorporating arsenic trioxide consolidation with reduced anthracycline dosing provide a new benchmark for outcome in pediatric patients with APL.—Zachary Bessette

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