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On 25 February 2019 at the Acute Leukemias XVII Biology and Treatment Strategies biennial symposium in Munich, Germany, Klaus Metzeler from the Ludwig Maximilian University of Munich, Munich, Germany, presented data from a study which aimed to validate the European LeukemiaNet (ELN) genetic risk stratification system in adult patients with acute myeloid leukemia (AML), who received cytarabine and anthracycline induction chemotherapy enrolled on acute myeloid leukemia cooperative group (AMLCG) trials.1,2
Overall, patients included in this study (n = 1118; median age = 58 years; range, 18–86) were analyzed in two cohorts. The incidence cohort (n = 772) included patients with all cytogenetic categories from the AMLCG-1999 and AMLCG-2008 studies, in genetically unselected patients. The extension cohort (n = 346) included patients with AML who had normal cytogenetic characteristics from the AMLCG-1999 study, with patients only included in the outcome analyses. Patients underwent genetic analysis, including sequencing for mutations in the NPM1, FLT3, CEBPA, RUNX1, ASXL1, and TP53 genes.
Data shown based on the ELN 2017 classification
Data shown from the refined ELN 2017 classification using established prognostic markers
Data shown from the refined ELN 2017 classification using the incorporation of additional pretreatment markers
In conclusion, the ELN 2017 classification allows validated genetic risk based stratification of patients with AML receiving cytarabine and anthracycline induction chemotherapy. Furthermore, the study concluded that more patients are classified with favorable or adverse risk AML, and less as intermediate risk AML compared to the ELN 2010 classification system. Moreover, this study illustrates the possibility for further refinement of the ELN 2017 genetic risk classification system. The relevance of the risk classification system is unclear in patients receiving alternative therapies, such as venetoclax, or the effect of molecularly targeted agents, as it has been established primarily in patients receiving induction chemotherapy. Klaus Metzeler stated the importance of integrating pre-treatment risk classification with the measures of response and residual disease post-treatment. This study highlights that the future challenge is the integration of a multidimensional model to effectively aid in the selection of the most promising sequence of therapies for patients with AML.
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