This PhD focuses on improving the understanding of acute myeloid leukemia (AML), a complex and aggressive blood cancer marked by recurrent genetic and chromosomal alterations. These alterations are central to how AML is classified, how prognosis is assessed, and how treatment decisions are made. However, much of the current knowledge stems from selected patient groups, which may not fully reflect real-world outcomes. To address this, the project established the REFORM-AML cohort, drawing on extensive national health data from Denmark to investigate AML in a broader, unselected population.

The thesis includes three studies exploring prognostic factors and treatment responses in AML. The first study validated the REFORM-AML cohort by comparing it with the wider Danish AML population, confirming its representativeness. It also analyzed differences in mutation patterns across age and sex and compared the prognostic performance of the ELN2017 and ELN2022 risk classifications, finding ELN2017 to be slightly more effective in predicting survival.

The second study focused on trisomy 8, a common chromosomal abnormality in AML. It found that patients with trisomy 8 consistently had poorer outcomes than those with a normal karyotype. Even when adjusting for genetic risk, trisomy 8 remained an independent marker of adverse prognosis. 

The third study examined the use of venetoclax (VEN) in combination therapies for patients with relapsed or refractory AML. VEN-based treatments led to high response rates across various genetic subgroups, and although survival outcomes were generally improved, the benefit was often short-lived.

Altogether, this PhD contributes real-world insights into how genetic alterations affect prognosis and treatment in AML. The REFORM-AML database serves as a robust platform for future research in high-risk myeloid diseases in Denmark and may also support international studies targeting rare genetic subtypes of AML.