Acute myeloid leukemia in the next-generation sequencing era : Real-world data from an Austrian tertiary cancer care center.

Autor: Wurm S; Clinical Division of Hematology, Medical University of Graz, Auenbruggerplatz 38, 8036, Graz, Austria., Waltersdorfer M; Clinical Division of Hematology, Medical University of Graz, Auenbruggerplatz 38, 8036, Graz, Austria., Loindl S; Clinical Division of Hematology, Medical University of Graz, Auenbruggerplatz 38, 8036, Graz, Austria., Moritz JM; Clinical Division of Hematology, Medical University of Graz, Auenbruggerplatz 38, 8036, Graz, Austria., Herzog SA; Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria., Bachmaier G; Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria., Berghold A; Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria., Kashofer K; Diagnostic & Research Institute of Pathology, Medical University of Graz, Graz, Austria., Beham-Schmid C; Diagnostic & Research Institute of Pathology, Medical University of Graz, Graz, Austria., Hoefler G; Diagnostic & Research Institute of Pathology, Medical University of Graz, Graz, Austria., Greinix HT; Clinical Division of Hematology, Medical University of Graz, Auenbruggerplatz 38, 8036, Graz, Austria., Wölfler A; Clinical Division of Hematology, Medical University of Graz, Auenbruggerplatz 38, 8036, Graz, Austria., Reinisch A; Clinical Division of Hematology, Medical University of Graz, Auenbruggerplatz 38, 8036, Graz, Austria.; Department of Blood Group Serology and Transfusion Medicine, Medical University of Graz, Graz, Austria., Sill H; Clinical Division of Hematology, Medical University of Graz, Auenbruggerplatz 38, 8036, Graz, Austria., Zebisch A; Clinical Division of Hematology, Medical University of Graz, Auenbruggerplatz 38, 8036, Graz, Austria. armin.zebisch@medunigraz.at.; Division of Pharmacology, Otto Loewi Research Center for Vascular Biology, Immunology, and Inflammation, Medical University of Graz, Graz, Austria. armin.zebisch@medunigraz.at.
Jazyk: angličtina
Zdroj: Wiener klinische Wochenschrift [Wien Klin Wochenschr] 2024 Nov 11. Date of Electronic Publication: 2024 Nov 11.
DOI: 10.1007/s00508-024-02463-w
Abstrakt: 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.
Competing Interests: Declarations Conflict of interest S. Wurm: honoraria: AbbVie; J.M. Moritz: honoraria: AbbVie;. A. Zebisch: honoraria: Bristol Myers Squibb, Otsuka, AbbVie, Novartis; consulting or advisory role: Bristol Myers Squibb, Astellas, AbbVie, Delbert Pharma, JAZZ, Novartis; Research Funding: Apollo Therapeutics; Travel accommodation: Astra Zeneca. A. Reinisch: honoraria: Bristol Myers Squibb, AbbVie, Novartis; consulting or advisory role: Bristol Myers Squibb, AbbVie. H. Sill: consulting or advisory role: Pfizer, AbbVie. A. Wölfler: honoraria: Abbvie, Bristol Myers Squibb, Pfizer, Astellas and Novartis; consulting or advisory role: Abbvie, Bristol Myers Squibb and Novartis. M. Waltersdorfer, S. Loindl, S.A. Herzog, G. Bachmaier, A. Berghold, K. Kashofer, C. Beham-Schmid, G. Hoefler and H.T. Greinix declare that they have no competing interests. Ethical standards For this article no studies with human participants or animals were performed by any of the authors. All studies performed were in accordance with the ethical standards indicated in each case. The study was approved by the institutional review board of the Med Uni Graz (EK 30-464 ex 17/18 and EK 35-079 ex 22/23). Every patient signed an informed consent for data recording and analysis, as well as for the biobanking of the respective specimens.
(© 2024. The Author(s).)
Databáze: MEDLINE
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