ATO enables anthracycline reduction in pediatric APL
And these results were achieved with a cumulative anthracycline dosing of idarubicin at 51 mg/m2 (SR) and 61 mg/m2 (HR) and mitoxantrone at 20 mg/m2.
This compared with the AIDA0493 cumulative anthracycline dosing of 80 mg/m2 of idarubicin and 50 mg/m2 of mitoxantrone.
The cumulative daunorubicin equivalent in the AAML0631 trial was 335 mg/m2 (SR) and 385 mg/m2 (HR) compared with 600 mg/m2 in the AIDA 0493 trial.
Toxicity
The percentage of patients with adverse events varied according to treatment cycle and was highest during induction and high-dose cytarabine-containing courses.
The most common adverse events were fever/neutropenia and infection.
Differentiation syndrome occurred in 20% of patients during induction, 31% in HR patients and 13% in SR patients. ATRA was held for 15 of these patients during induction. It was subsequently re-started at a lower dose and increased to the full dose.
QTc interval prolongation of grade 1 or 2 occurred in 16% (n=15) and 12% (n=11) during the ATO cycles.
One patient experienced grade 3 QTc interval prolongation during ATO consolidation. There were no grade 4 or 5 events for this toxicity.
One event of grade 1 ventricular arrhythmia and 1 event of grade 1 left ventricular systolic dysfunction occurred during ATO consolidation.
Two off-therapy cardiac events have been reported: a grade 1 QTc interval prolongation and a grade 2 ventricular arrhythmia.
No cardiac deaths have occurred, and liver toxicity was minimal during ATO cycles.
The investigators believe the favorable results of this study provide a new benchmark for outcomes in pediatric APL.
The Children’s Oncology Group is currently accruing pediatric APL patients to further investigate similar treatment approaches. 
