Real-world genomic profiling of acute myeloid leukemia and the impact of European LeukemiaNet risk stratification 2022 update

Abstract

Background: Acute myeloid leukemia (AML) is a myeloid neoplasm associated with a high morbidity and mortality. The diagnosis, risk stratification and therapy selection in AML have changed substantially in the last decade with the progressive incorporation of clinically relevant molecular markers.

Methods: In this work, our aim was to describe a real-world genomic profiling experience in AML and to demonstrate the impact of the European Leukemia Net 2022 update on risk stratification in AML.

Results and discussion: One hundred and forty-one patients were evaluated with an amplicon-based multi-gene next-generation sequencing (NGS) panel. The most commonly mutated genes were FLT3, DNMT3A, RUNX1, IDH2, NPM1, ASXL1, SRSF2, NRAS, TP53 and TET2. Detection of FLT3 ITD with NGS had a sensitivity of 96.3% when compared to capillary electrophoresis. According to ELN 2017, 26.6%, 20.1%, and 53.3% of patients were classified as having a good, moderate, or unfavorable risk. When ELN 2022 was used, 15.6%, 27.8%, and 56.6% of patients were classified as favorable, moderate, or unfavorable risk, respectively. When ELN 2022 was compared to ELN 2017, thirteen patients (14.4%) exhibited a different risk classification, with a significant decrease in the number of favorable risk patients, what has immediate clinical impact.

Conclusions: In conclusion, we have described a real-world genomic profiling experience in AML and the impact of the 2022 ELN update on risk stratification.

Keywords: Acute myeloid leukemia; Genetics.