Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Wurm, S; Waltersdorfer, M; Loindl, S; Moritz, JM; Herzog, SA; Bachmaier, G; Berghold, A; Kashofer, K; Beham-Schmid, C; Hoefler, G; Greinix, HT; Wölfler, A; Reinisch, A; Sill, H; Zebisch, A.
Acute myeloid leukemia in the next-generation sequencing era : Real-world data from an Austrian tertiary cancer care center.
Wien Klin Wochenschr. 2024;
Doi: 10.1007/s00508-024-02463-w
Web of Science
PubMed
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- Führende Autor*innen der Med Uni Graz
- Wurm Sonja
- Zebisch Armin
- Co-Autor*innen der Med Uni Graz
- Bachmaier Gerhard
- Beham-Schmid Christine
- Berghold Andrea
- Greinix Hildegard
- Herzog Sereina Annik
- Höfler Gerald
- Kashofer Karl
- Neiss Jennifer Monika
- Reinisch Andreas
- Sill Heinz
- Wölfler Albert
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- Abstract:
- BACKGROUND: Next-generation sequencing (NGS) has recently entered routine acute myeloid leukemia (AML) diagnostics. It is paramount for AML risk stratification and identification of molecular therapeutic targets. Most NGS feasibility and results data are derived from controlled clinical intervention trials (CCIT). We aimed to validate these data in a real-world setting. PATIENTS, MATERIALS AND METHODS: This study retrospectively analyzed 447 AML patients treated at an Austrian tertiary cancer care center. A total of 284 out of the 447 cases were treated between 2013-2023 when NGS was locally available for the clinical routine. RESULTS: The NGS was successfully performed from bone marrow biopsies and aspirates, with processing times decreasing from 22 days in 2013/2014 to 10 days in 2022. Molecular therapeutic target(s) were identified by NGS in 107/284 (38%) cases and enabled risk stratification in 10 cases where conventional karyotyping failed. Concerning molecular landscape, TET2 (27%), FLT3 (25%), DNMT3A (23%), and NPM1 (23%) were most frequently mutated. Comparing older and younger patients (cut-off 70 years) showed enrichment in older people for mutations affecting DNA methylation (72% vs. 45%; P < 0.001) and the spliceosome (28% vs. 11%; P = 0.006) and more cellular signaling mutations in younger patients (61% vs. 46%; P = 0.022). Treatment outcomes corroborated a significant survival benefit in the recent NGS era and patients treated with novel/molecularly targeted drugs. Ultimately, biospecimens of these patients are stored within a leukemia biobank, generating a valuable tool for translational science. CONCLUSION: Our study validates data from CCIT and supports their relevance for treatment decisions in a real-world setting. Moreover, they demonstrate the feasibility and benefits of NGS within a routine clinical setting.
- Find related publications in this database (Keywords)
- AML
- Mutational profile
- Controlled clinical trials
- Real-world data
- Leukemia biobank