Risk-adapted treatment of acute promyelocytic leukemia

Pediatric acute promyelocytic leukemia (APL) can be cured with all-trans retinoic acid (ATRA) and anthracycline. However, most published trials have employed high cumulative doses of anthracyclines. Here, we report the outcome of newly diagnosed APL patients enrolled in the International Consortium for Childhood APL (ICC-APL-01) trial, which reduced anthracycline exposure but extended that of ATRA. The study recruited 258 children/adolescents with molecularly/cytogenetically proven APL. Patients were stratified into standard-risk (SR) and high-risk (HR) groups according to baseline white blood cell counts (<10 × 109/L or ≥10 × 109/L); both groups received identical induction treatment with ATRA and 3 doses of idarubicin. Two or 3 blocks of consolidation therapy were administered to SR and HR patients, respectively, while maintenance therapy with low-dose chemotherapy and ATRA cycles was given to all patients for 2 years. The cumulative dose of daunorubicin equivalent anthracyclines in SR and HR patients was lower than that of previous studies (355 mg/m2 and 405 mg/m2, respectively). Hematologic remission was obtained in 97% of patients; 8 children died of intracranial hemorrhage in the first 2 weeks following diagnosis. Five-year overall and event-free survival for the whole cohort were 94.6% and 79.9%, respectively; they were 98.4% and 89.4% in SR patients and 84.3% and 74.2% in HR patients (P = .002 and P = .043, respectively). These data demonstrate that extended use of ATRA coupled to a risk-adapted consolidation can achieve high cure rates in childhood APL and limit anthracycline exposure. The trial was registered at www.clinicaltrials.gov as EudractCT 2008-002311-40.