Induction-phase blood arsenic concentration and relapse risk in pediatric APL treated with arsenic and ATRA

The application of targeted therapy with arsenic and all-trans retinoic acid (ATRA) has significantly improved outcomes in pediatric acute promyelocytic leukemia (APL), but relapse remains a major obstacle to cure. This study aimed to identify risk factors for relapse in pediatric APL and to evaluate the relationship between arsenic concentration and relapse. In this multicenter retrospective study, a total of 566 pediatric patients with newly diagnosed APL treated with the CCLG-APL 2016 or CCLG-APL 2018 protocol were enrolled. The median follow-up was 68.0 months, and 44 patients experienced relapse. The analysis showed complex karyotypes (≥ 3 additional chromosomal abnormalities) (HR = 3.238, 95% CI: 1.134–9.244, P  = 0.028) and MCR ≥ 72 days (HR = 1.995, 95% CI: 1.132–3.757, P  = 0.024) were independent risk factors for relapse. Logistic regression indicated that arsenic trioxide (ATO) used during induction was associated with a lower relapse risk compared to Realgar-Indigo naturalis formula (RIF) (OR = 0.310, 95% CI: 0.105–0.916, P  = 0.034]. In 64 patients with arsenic monitoring, blood arsenic levels on days 7, 14, and 28 were significantly higher in ATO group than the RIF group (all P  < 0.01), and were significantly lower in the relapse group compared to the non-relapse group ( P  = 0.031, 0.036, 0.034, respectively). ROC analysis identified a blood arsenic cutoff of < 25.6 ng/mL after 7 days of induction as predictive of higher relapse risk. Our study confirmed risk factors for relapse in pediatric APL, and suggested that maintaining a blood arsenic concentration ≥ 25.6 ng/mL after seven days of induction may be beneficial for prognosis.