A Multicenter Clinical Study of Cccg - APL-2017 in the Treatment of Children with Acute Promyelocytic Leukemia

The standard therapy for childhood acute promyelocytic leukemia (APL) involves the combination of all-trans retinoic acid (ATRA) with arsenic trioxide (ATO) or Compound Huangdai tablet (Realgar-Indigo Naturalis formula, RIF). However, the effectiveness and safety of combining RIF with ATRA in a larger population of pediatric APL patients remains undocumented. Additionally, there is variability in the oral timing and dosage of RIF in different studies, which should be standardized. We conducted a multicenter clinical trial (ChiCTR-OIC-16010014) in China. Individuals newly diagnosed with APL were categorized into two risk groups based on their initial white blood cell (WBC) count. Those with a WBC count exceeding 5×10^9/L received hydroxycarbamide at a dosage ranging from 20 to 50 mg/kg per day until their WBC levels dropped to 10×10^9/L or lower. The primary outcomes assessed were event-free survival (EFS) and overall survival (OS) over six years. We recruited 200 patients diagnosed with APL. After a median follow-up time of 43.2 months, it was observed that the six-year OS rate was 100% in the low-risk cohort and 97.6% in the high-risk cohort. The six-year EFS rate was found to be 98.3% in the low-risk group and 97.6% in the high-risk group. It was observed that plasma levels of arsenic remained stable after the administration of RIF at a dosage of 60 mg/kg/d for seven days and returned to baseline levels within fourteen days after discontinuation of RIF administration. Furthermore, treatment strategies aimed at controlling WBC counts to maintain levels at or below 30×10^9/L were found to reduce the incidence of induced differentiation syndrome (DS) or alleviate its associated symptoms. In conclusion, The CCCG-APL-2017 regimen, which combines RIF with ATRA, demonstrates both efficacy and safety in treating children with APL. A dosage of 60mg/kg/d of RIF is considered sufficient for the management of pediatric APL.