Risk-adapted treatment of acute promyelocytic leukemia: results from the International Consortium for Childhood APL

Abstract

Pediatric acute promyelocytic leukemia (APL) can be cured with all- 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 × 10/L or ≥10 × 10/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/m and 405 mg/m, 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 ( = .002 and = .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.

Treatment Outcome and the Genetic Characteristics of Acute Promyelocytic Leukemia in Children in Poland From 2005 to 2018

“…In the analyzed period, the percentage of the patients with APL among all children with AML in Poland was 6.5%. The treatment results achieved in the study group (OS, 0.832 ± 0.069; EFS, 0.848 ± 0.066; RFS, 0.964 ± 0.035) are comparable to the results described by other authors (1,2,7,8,13,16,17); however, the number of enrolled patients is relatively low. The data concerning molecular monitoring were limited in period I so comparison between two groups was not possible.…”

“…The combination of ATRA, ATO, and anthracycline-based chemotherapy ensures remission achievement in almost all patients (1,(13)(14)(15)(16). Use of the specific treatment in APL allowed reduction of the chemotherapy especially cumulative anthracycline doses (13,(15)(16)(17). The main causes of the treatment failure are still early deaths, mostly in the course of intracranial hemorrhage (2,3,18).…”

Clinical Characteristics and Treatment Outcomes of Childhood Acute Promyelocytic Leukemia in Korea: A Nationwide Multicenter Retrospective Study by Korean Pediatric Oncology Study Group

“…therapeutic efficacy and pharmacokinetic results [17]. For this reason, many protocols for the treatment of pediatric APL have since used ATRA at a dose of 25 mg/m 2 /d, and the treatment outcomes were reported to be similar to those who received conventional dose ATRA [7,9,14].…”

Exploiting Clonal Evolution to Improve the Diagnosis and Treatment Efficacy Prediction in Pediatric AML

“…These include the translocation t(15;17)(q24.1;q21.2), that leads to the fusion of promyelocytic leukemia (PML) gene with the retinoic acid receptor alpha (RARA), in acute promyelocytic leukemia, which represent 5% of pediatric AML [9]. This subtype of AML is highly peculiar and does not belong to any additional category, and its remission rates are >95% and overall survival is >80% [10], thanks to a target therapy consisting of all-trans-retinoic acid (ATRA) associated with arsenic trioxide (ATO), with the addition of the anti-CD33 gemtuzumabozogamicin in high-risk patients, defined as having WBC prior to treatment ≥10 × 109/L [9]. Other subtypes of pediatric AML, characterized by a favorable prognosis, are those involving core binding factor (CBF), accounting for approximately 20-25% of pediatric Other subtypes of pediatric AML, characterized by a favorable prognosis, are those involving core binding factor (CBF), accounting for approximately 20-25% of pediatric AML cases [11], such as t(8;21) (q22;q22) and inv (16),which lead to the fusion genes RUNX1-RUNX1T1 and CBFB-MYH11, respectively.…”