Europeanpediatric Acute Leukemia (EuPAL) Registry

Abstract

The Leukemia Lymphoma Society (LLS) Pediatric Acute Leukemia (PedAL) Initiative is a collaborative international effort that aims to improve the cure of children with relapsed/refractory (R/R) and other high-risk leukemias. Its comprehensive approach included preclinical and clinical research, standardization and improvement of diagnostics, quality management, and global data integration and analysis. The European Pediatric Acute Leukemia (EuPAL) Foundation was established as the PedAL Initiative partner to support European stakeholders in these efforts. A major focus of the EuPAL Registry and PedAL Initiative is to increase access to and test new drugs targeting leukemia-specific biologic and genetic characteristics in pediatric patients with R/R acute myeloid leukemia (AML). However, identification and recruitment of patients remains a challenge. For this purpose, the APAL2020SC screening trial (NCT04726241) in North America, Australia, and New Zealand and the EuPAL registry in Europe have been launched. In collaboration with national and international study groups, pediatric leukemia reference laboratories, and participating clinical trial sites, each child with R/R AML should be registered. In Europe, the EuPAL registry office identifies the best available trial for the patient based upon leukemia-associated genetic and immunophenotypic data and closest trial site(s) and coordinates contact between the treating physician/site and the trial site as needed. Results The EuPAL registry has been approved by the leading ethic committee in Germany with extension to several other European countries ongoing. To date, 35 children and adolescents with R/R AML have been enrolled since June 2022. The median age at initial diagnosis was 7.3 (range 0.2 to 17.7) years with median duration of remission 1.3 (0.3 to 5.3) years. Most patients were registered at first relapse (n=29) with 3 patients in second relapse and 1 patient in third relapse. Two children were diagnosed with a molecular relapse (n=2). Fourteen patients have been transplanted in 1 st CR (n=9) /2 nd CR (n=5) prior to registration Regarding the initial risk groups at diagnosis, most relapses occurred in the intermediate risk group (IR) n=19) and the high-rik group (HR; n=12). The others were standard risk, one isolated CNS relapse in APL and two in children with trisomy 21. Patients were treated at relapse on the AML-BFM 2017 registry (treatment recommendation: Idarubicin, fludarabine, cytarabine (IDA-FLA), FLA and HSCT), the AIEOP-BFM-AML 2020 trial (FLA- gemtuzumab ozogamicin (GO) or IDA-FLA t(8;21)), the AMORE 2017 trial (azacytidine and HSCT; n=2) or received off-label therapies (cytarabine/GO, venetoclax/cytarabine, or azacytidine). Conclusion The EuPAL registry has been successfully established and is beginning to generate relevant knowledge regarding the frequency and timing of pediatric AML relapse, leukemia-associated genetics, and immunophenotypic characteristics. In collaboration with the LLS PedAL Initiative, the EuPAL registry will continue to facilitate recruitment of children with R/R AML and other leukemias to clinical trials testing innovative therapies, as well as improve understanding of potential bias in clinical trial referrals. Current challenges include integration of more European countries into the EuPAL Registry and increasing the number of open early-phase PedAL/EuPAL clinical trials.