Validation and refinement of the 2022 European LeukemiaNet genetic risk stratification of acute myeloid leukemia
© 2023. The Author(s)..
The revised 2022 European LeukemiaNet (ELN) AML risk stratification system requires validation in large, homogeneously treated cohorts. We studied 1118 newly diagnosed AML patients (median age, 58 years; range, 18-86 years) who received cytarabine-based induction chemotherapy between 1999 and 2012 and compared ELN-2022 to the previous ELN-2017 risk classification. Key findings were validated in a cohort of 1160 mostly younger patients. ELN-2022 reclassified 15% of patients, 3% into more favorable, and 12% into more adverse risk groups. This was mainly driven by patients reclassified from intermediate- to adverse-risk based on additional myelodysplasia-related mutations being included as adverse-risk markers. These patients (n = 79) had significantly better outcomes than patients with other adverse-risk genotypes (5-year OS, 26% vs. 12%) and resembled the remaining intermediate-risk group. Overall, time-dependent ROC curves and Harrel's C-index controlling for age, sex, and AML type (de novo vs. sAML/tAML) show slightly worse prognostic discrimination of ELN-2022 compared to ELN-2017 for OS. Further refinement of ELN-2022 without including additional genetic markers is possible, in particular by recognizing TP53-mutated patients with complex karyotypes as "very adverse". In summary, the ELN-2022 risk classification identifies a larger group of adverse-risk patients at the cost of slightly reduced prognostic accuracy compared to ELN-2017.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:37 |
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| Enthalten in: |
Leukemia - 37(2023), 6 vom: 11. Juni, Seite 1234-1244 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Rausch, Christian [VerfasserIn] |
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| Links: |
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| Themen: |
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| Anmerkungen: |
Date Completed 08.06.2023 Date Revised 22.06.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41375-023-01884-2 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM355456540 |
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| 245 | 1 | 0 | |a Validation and refinement of the 2022 European LeukemiaNet genetic risk stratification of acute myeloid leukemia |
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| 520 | |a © 2023. The Author(s). | ||
| 520 | |a The revised 2022 European LeukemiaNet (ELN) AML risk stratification system requires validation in large, homogeneously treated cohorts. We studied 1118 newly diagnosed AML patients (median age, 58 years; range, 18-86 years) who received cytarabine-based induction chemotherapy between 1999 and 2012 and compared ELN-2022 to the previous ELN-2017 risk classification. Key findings were validated in a cohort of 1160 mostly younger patients. ELN-2022 reclassified 15% of patients, 3% into more favorable, and 12% into more adverse risk groups. This was mainly driven by patients reclassified from intermediate- to adverse-risk based on additional myelodysplasia-related mutations being included as adverse-risk markers. These patients (n = 79) had significantly better outcomes than patients with other adverse-risk genotypes (5-year OS, 26% vs. 12%) and resembled the remaining intermediate-risk group. Overall, time-dependent ROC curves and Harrel's C-index controlling for age, sex, and AML type (de novo vs. sAML/tAML) show slightly worse prognostic discrimination of ELN-2022 compared to ELN-2017 for OS. Further refinement of ELN-2022 without including additional genetic markers is possible, in particular by recognizing TP53-mutated patients with complex karyotypes as "very adverse". In summary, the ELN-2022 risk classification identifies a larger group of adverse-risk patients at the cost of slightly reduced prognostic accuracy compared to ELN-2017 | ||
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| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 700 | 1 | |a Rothenberg-Thurley, Maja |e verfasserin |4 aut | |
| 700 | 1 | |a Dufour, Annika |e verfasserin |4 aut | |
| 700 | 1 | |a Schneider, Stephanie |e verfasserin |4 aut | |
| 700 | 1 | |a Gittinger, Hanna |e verfasserin |4 aut | |
| 700 | 1 | |a Sauerland, Cristina |e verfasserin |4 aut | |
| 700 | 1 | |a Görlich, Dennis |e verfasserin |4 aut | |
| 700 | 1 | |a Krug, Utz |e verfasserin |4 aut | |
| 700 | 1 | |a Berdel, Wolfgang E |e verfasserin |4 aut | |
| 700 | 1 | |a Woermann, Bernhard J |e verfasserin |4 aut | |
| 700 | 1 | |a Hiddemann, Wolfgang |e verfasserin |4 aut | |
| 700 | 1 | |a Braess, Jan |e verfasserin |4 aut | |
| 700 | 1 | |a von Bergwelt-Baildon, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Spiekermann, Karsten |e verfasserin |4 aut | |
| 700 | 1 | |a Herold, Tobias |e verfasserin |4 aut | |
| 700 | 1 | |a Metzeler, Klaus H |e verfasserin |4 aut | |
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