Paediatric Strategy Forum for medicinal product development for acute myeloid leukaemia in children and adolescents: ACCELERATE in collaboration with the European Medicines Agency with participation of the Food and Drug Administration.

PURPOSE: The current standard-of-care for front-line therapy for acute myeloid leukaemia (AML) results in short-term and long-term toxicity, but still approximately 40% of children relapse. Therefore, there is a major need to accelerate the evaluation of innovative medicines, yet drug development continues to be adult-focused. Furthermore, the large number of competing agents in rare patient populations requires coordinated prioritisation, within the global regulatory framework and cooperative group initiatives. METHODS: The fourth multi-stakeholder Paediatric Strategy Forum focused on AML in children and adolescents. RESULTS: CD123 is a high priority target and the paediatric development should be accelerated as a proof-of-concept. Efforts must be coordinated, however, as there are a limited number of studies that can be delivered. Studies of FLT3 inhibitors in agreed paediatric investigation plans present challenges to be completed because they require enrolment of a larger number of patients than actually exist. A consensus was developed by industry and academia of optimised clinical trials. For AML with rare mutations that are more frequent in adolescents than in children, adult trials should enrol adolescents and when scientifically justified, efficacy data could be extrapolated. Methodologies and definitions of minimal residual disease need to be standardised internationally and validated as a new response criterion. Industry supported, academic sponsored platform trials could identify products to be further developed. The Leukaemia and Lymphoma Society PedAL/EUpAL initiative has the potential to be a major advance in the field. CONCLUSION: These initiatives continue to accelerate drug development for children with AML and ultimately improve clinical outcomes.

Comparison of Arkray/ELITech ADAMS HA-8180V with Bio-Rad Variant, II Turbo2.0 and Tosoh Bioscience HLC-723G8 for HbA1c determination.

OBJECTIVE: This study aimed to evaluate a new ion-exchange HPLC system to measure hemoglobin A1c (HbA1c) in comparison to two other widely used HPLC systems. METHODS: Analytical performance and hemoglobin variants detection was assessed on the new Arkray/ELITech ADAMS HA-8180V, in parallel to Bio-Rad Variant II Turbo2.0 and Tosoh Bioscience HLC-723G8. A method comparison and concordance for the classification of patients according to the American Diabetes Association (ADA) categories was performed using kappa test. RESULTS: ADAMS HA-8180V demonstrated excellent within-run imprecision (0%) and between-run imprecision: ≤1.21% using blood sample and ≤0.94% using quality controls. Method comparison of ADAMS HA-8180V with the two other systems yielded very high coefficient correlation (r > 0.995). A very good agreement (kappa value ≥0.81) was observed between methods for the classification of patients according to the ADA categories. In addition, all systems were able to detect the presence of most classical variants such as HbC, HbS, HbD, and HbE. CONCLUSION: The Arkray/ELITech ADAMS HA-8180V demonstrated high analytical performance similar to previous systems such as Biorad(TM) Variant II Turbo 2.0 and Tosoh Bioscience HLC-723G8. The three systems allow a high-quality HbA1c measurement and appeared interchangeable for diabetes diagnosis or for the therapeutic monitoring of patients without hemoglobin variants.