Arsenic Trioxide and Reduced Anthracycline Dose in Pediatric Acute Promyelocytic Leukemia


Key Points

  • Overall and event-free survival at 3 years was 94% and 91% among all pediatric patients with APL treated with arsenic trioxide consolidation and a lower-dose anthracycline.
  • The regimen was noninferior in event-free survival vs a historical control regimen using markedly higher anthracycline doses.

In the phase III historically controlled Children’s Oncology Group (COG) AAML0631 trial, arsenic trioxide consolidation permitted the use of lower-dose anthracycline without appearing to compromise outcomes in pediatric patients with acute promyelocytic leukemia (APL). The results were reported in the Journal of Clinical Oncology by Kutny et al.

Study Details

In the study, 101 evaluable patients aged 2 to 21 years with de novo APL received all-trans retinoic acid (ATRA) during induction, each consolidation course, and maintenance; all patients received two cycles of arsenic trioxide during consolidation one; an additional two (standard-risk patients, n = 66) or three (high-risk patients, n = 35) consolidation courses that included high-dose cytarabine and anthracycline; and maintenance therapy consisting of ATRA, oral methotrexate, and mercaptopurine. Patients were stratified as standard- or high-risk based on diagnostic white blood cell counts.

Survival Outcomes

At 3 years, overall survival was 94%, and event-free survival was 91%; for standard- vs high-risk patients, the rates were 98% vs 86% (P = .003) and 95% vs 83% (P = .03), respectively. Patients received an anthracycline dose approximately 40% lower than that in the historical control AIDA 0493 trial, which did not include arsenic trioxide consolidation. Two-year event-free survival in the AIDA trial was used as a benchmark for the standard-risk group in the COG trial; 2-year rates were 97% in the current trial (including molecular relapse as an event) vs 91% in the AIDA trial (which censored molecular relapse), with the difference meeting the COG protocol’s predetermined statistical criteria for noninferiority (P = .93).

The 3-year relapse risk from the end of consolidation one, after arsenic trioxide treatment, was 4%, with no difference observed between standard- and high-risk patients.

The investigators concluded: “[Arsenic trioxide] consolidation cycles were well tolerated in pediatric patients with APL and allowed significant reduction in cumulative anthracycline doses while maintaining excellent survival and a low relapse risk for both [standard-risk] and [high-risk] patients with APL.”

The study was supported by grants from the National Cancer Institute, St Baldrick’s Foundation, and Andrew McDonough B+ Foundation.

Matthew A. Kutny, MD, of the University of Alabama at Birmingham, is the corresponding author of the Journal of Clinical Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.