ORLANDO, FLPhase 3 study results from a Children’s Oncology Group trial strongly support the use of arsenic trioxide consolidation for children newly diagnosed with acute promyelocytic leukemia (APL), according to a presentation at the 57th American Society of Hematology (ASH) Annual Meeting.1

“The excellent molecular remission rate at end of consolidation and the low relapse rate confirm the effectiveness of this therapy,” said Matthew A. Kutny, MD, of the University of Alabama at Birmingham.

The study achieved higher rates of event-free survival in both standard risk and higher risk APL by incorporating 2 cycles of arsenic trioxide during consolidation. In addition, anthracycline dosing was reduced by approximately 40% compared with historical control, an Italian trial with the largest patient cohort and best phase 3 results for pediatric APL to date.

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Between March 2009 and November 2012, the study enrolled 108 patients between 2 and 22 years of age with de novo APL confirmed by PML-RARA PCR who were treatment-naïve; 101 were evaluable for outcome. Diagnostic white blood cell count (WBC) categorized patients as standard risk for WBC less than 10,000 (66 patients) or high risk for WBC 10,000 or higher (35 patients).

Two cycles of arsenic trioxide 0.15 mg/kg/day IV 5 days each week for 5 weeks was administered during the first of 4 consolidation cycles following induction therapy.

After induction, hematologic complete remission (CR) was 81%, Dr. Kutny reported, while molecular (RQ-PCR) remission at end of consolidation was 100%.

“The reported CR rate was lower than historical comparisons, but this was likely due to difficulty in assessing differentiating and recovering bone marrow cells after APL induction,” he said.

At 2 years, overall survival was 94% and event-free survival was 91%. When patients in the standard risk group were compared to those in the high risk group, overall survival was 98% vs 86% (P = .003) and event-free survival was 95% vs 83% (P = .030), respectively. The comparable 3-year event-free survival rate for the historical control study was 90% for the standard risk and 71% for the high risk group.

Relapse risk did not differ significantly between patients with standard risk versus high risk APL (P = .226).

During the study, there were 3 relapses (2 high risk and 1 standard risk), 2 second malignant neoplasm (squamous cell carcinoma in situ and secondary acute myeloid leukemia) and 7 deaths, 6 in the high-risk group and 1 in the standard-risk group, including 1 death post-relapse.


1. Kutny MA, Alonzo TA, Gerbing RB, et al. Results of a phase III trial including arsenic trioxide consolidation for pediatric patients with acute promyelocytic leukemia (APL): a report from the Children’s Oncology Group Study AAML0631. Oral presentation at: 57th American Society of Hematology (ASH) Annual Meeting; December 6, 2015, Orlando, FL.