Clinical characteristics and outcome of pediatric patients with high-risk acute promyelocytic leukemia, with special focus on risk factors of early death

To evaluate the real-life outcome of pediatric high-risk acute promyelocytic leukemia (APL) after up-front treatment with all-trans retinoic acid (ATRA) and arsenic trioxide. Thirty-two pediatric patients diagnosed with high-risk APL from 2015 to 2022 were retrospectively studied. Of the 326 children with acute myeloid leukemia, 86 (26.4%) were diagnosed with APL. Thirty-two patients (37.2%) were designated to the high-risk group at diagnosis. Seven patients (21.8%) died during induction chemotherapy and the other 25 patients all achieved molecular complete remission (MCR) after induction chemotherapy. The underlying causes of early death (ED) were identified as follows: six cases of intracranial hemorrhage, and one case of pneumorrhagia accompanied by differentiation syndrome. Six ED cases developed fatal hemorrhage after the rapid initiation of ATRA. After a median follow-up duration of 50.1 months, the 5-year overall survival (OS) and event-free survival (EFS) rates were estimated to be (78.1 ± 7.3)% and (72.9 ± 8.5)%, respectively. Patients with ED had significantly higher rate of WBC count ≥ 50 × 10⁹/L (P = 0.027), female -to-male ration (P = 0.036), and prothrombin time (PT) ≥ 18 S (P = 0.017), along with shorter symptom-to-ATRA intervals (P = 0.014). ED remains the primary threat in high-risk APL, associated with elevated WBCs, prolonged PT, female gender and rapid disease progression. The inability of ATRA to prevent death in some cases may be due to individual variability and leukemia heterogeneity.