Comparative prognostic performance of ELN 2022 and ELN 2024 risk classifications in a Turkish cohort of acute myeloid leukemia patients receiving hypomethylating agents and BCL-2 inhibitors

Abstract

Objective: The European LeukemiaNet (ELN) 2022 risk classification for acute myeloid leukemia (AML) was primarily developed in cohorts treated with intensive chemotherapy and has demonstrated limited prognostic discrimination in AML patients receiving less-intensive regimens. The recently proposed ELN 2024 classification aims to refine risk stratification in patients treated with less-intensive regimens. We compared the prognostic performance of ELN 2022 and ELN 2024 in a real-world cohort of unfit AML patients treated with azacitidine plus venetoclax.

Materials and Methods: In this retrospective single-center study, 39 newly diagnosed AML patients treated with first-line azacitidine and venetoclax between January 2023 and September 2025 were included. Patients were stratified according to ELN 2022 and ELN 2024 criteria. Overall survival (OS) was analyzed using Kaplan–Meier estimates, log-rank tests, Cox regression, and Harrell’s concordance index (C-index).

Results: Median age was 70 years (range, 60–84). Secondary AML was present in 33.3%, and 30.8% harbored TP53 mutations. Under ELN 2022, 64.1% of patients were classified as adverse risk compared with 30.8% under ELN 2024. ELN 2022 did not significantly stratify OS in either three-group or dichotomized analyses (p=0.265 and p=0.199, respectively). In contrast, dichotomized ELN 2024 demonstrated significant survival separation (p=0.041). Adverse risk according to ELN 2024 was associated with inferior OS (HR 2.41, 95% CI 0.98–5.94; p=0.057). The highest discriminatory capacity was observed with the dichotomized ELN 2024 model (C-index 0.697; p=0.021).

Conclusion: In AML patients treated with hypomethylating agents plus venetoclax, ELN 2024 provides improved prognostic discrimination compared with ELN 2022. These findings support the clinical relevance of treatment-context–specific risk stratification in the venetoclax era.