Genomic and clinical determinants of outcome in Irish AML: a real-world analysis (2007-2025), single centre...

Acute myeloid leukaemia (AML) is a genetically heterogeneous malignancy in which cytogenetic and molecular features critically inform diagnosis, prognosis, and therapeutic decision-making. While traditional karyotyping has long guided risk stratification, high-throughput sequencing has revealed extensive molecular diversity, particularly within cytogenetically normal AML, reshaping AML classification and management. This study characterises the genomic landscape and clinical outcomes of an Irish AML cohort using integrated cytogenetic and molecular profiling. We retrospectively analysed 166 adult AML patients diagnosed at our cancer centre between 2007 and 2025. Demographic, clinical, cytogenetic, molecular, and treatment data were collected. Karyotype-based and ELN 2022/2024 molecular classifications were applied. Survival analyses were performed using Prism v10.06, with statistical significance assessed using the log-rank (Mantel-Cox) test. Mutation frequencies were compared with published literature, and genomic subgroups were examined for prognostic impact. The median age at diagnosis was 70 years (range 24-92), with 68% de novo AML, 19% secondary AML, 10% therapy-related AML, and 3% APL. Of 126 treated patients, 72 received intensive therapy and 53 received less-intensive regimens. CR rates were 75% in the intensive cohort versus 36% in the less-intensive cohort. Karyotyping (available in 87%) revealed 47% with normal cytogenetics, favourable risk in 5% and 30% with adverse-risk features. Molecular profiling identified ELN 2022 adverse-, intermediate-, and favourable-risk categories in 42%, 47%, and 7% of intensively treated patients; in the less-intensive cohort, adverse risk predominated (87%). TP53 mutations occurred in 8% of the entire cohort. Median OS and PFS were 19 and 11 months, respectively. Younger age (<65 years), favourable / intermediate cytogenetics, de novo AML, favourable / intermediate-risk ELN 2022 classification, and TP53 wild-type status were associated with significantly superior survival (all P < 0.05). Intensive therapy conferred marked survival benefit (median OS 32 vs 9 months; HR 0.35, P < 0.0001). ELN 2024 risk groups did not discriminate survival in the less-intensive cohort. TP53 mutations were associated with significantly inferior OS (median 12 vs 23 months; P = 0.008). This single-centre study demonstrates a heterogeneous genomic landscape in Irish AML patients, with mutation frequencies broadly consistent with international datasets but with notable enrichment of adverse-risk disease in older and less-intensively treated populations. Integrated cytogenetic and molecular profiling strongly predicted outcomes, while age, treatment intensity, and TP53 status emerged as dominant prognostic factors. These findings highlight the critical value of comprehensive genomic assessment to guide stratified AML management within the Irish population.