Validation and refinement of the 2022 European LeukemiaNet genetic risk stratification of acute myeloid leukemia
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 a...
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| Veröffentlicht in: | Leukemia 2023-06, Vol.37 (6), p.1234-1244 |
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| creator | Rausch, Christian Rothenberg-Thurley, Maja Dufour, Annika Schneider, Stephanie Gittinger, Hanna Sauerland, Cristina Görlich, Dennis Krug, Utz Berdel, Wolfgang E. Woermann, Bernhard J. Hiddemann, Wolfgang Braess, Jan von Bergwelt-Baildon, Michael Spiekermann, Karsten Herold, Tobias Metzeler, Klaus H. |
| description | 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. |
| doi_str_mv | 10.1038/s41375-023-01884-2 |
| format | Article |
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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.</description><identifier>ISSN: 0887-6924</identifier><identifier>EISSN: 1476-5551</identifier><identifier>DOI: 10.1038/s41375-023-01884-2</identifier><identifier>PMID: 37041198</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>45/23 ; 692/499 ; 692/699/67/1990/283/1897 ; 692/699/67/69 ; Acute myeloid leukemia ; Cancer Research ; Cancer therapies ; Chemotherapy ; Classification ; Clinical trials ; Critical Care Medicine ; Cytarabine ; Genetic markers ; Genotypes ; Hematology ; Intensive ; Internal Medicine ; Karyotypes ; Leukemia ; Medical research ; Medicine ; Medicine & Public Health ; Mutation ; Myelodysplastic syndrome ; Oncology ; p53 Protein ; Patients ; Risk ; Risk groups</subject><ispartof>Leukemia, 2023-06, Vol.37 (6), p.1234-1244</ispartof><rights>The Author(s) 2023</rights><rights>2023. The Author(s).</rights><rights>The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c475t-9133420f486853ef73cbb9bd100c967d2ce18ba79d9509a12f9a6de0db371e1b3</citedby><cites>FETCH-LOGICAL-c475t-9133420f486853ef73cbb9bd100c967d2ce18ba79d9509a12f9a6de0db371e1b3</cites><orcidid>0000-0003-3920-7490 ; 0000-0002-9615-9432 ; 0000-0002-7364-5526 ; 0000-0002-5139-4957</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37041198$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rausch, Christian</creatorcontrib><creatorcontrib>Rothenberg-Thurley, Maja</creatorcontrib><creatorcontrib>Dufour, Annika</creatorcontrib><creatorcontrib>Schneider, Stephanie</creatorcontrib><creatorcontrib>Gittinger, Hanna</creatorcontrib><creatorcontrib>Sauerland, Cristina</creatorcontrib><creatorcontrib>Görlich, Dennis</creatorcontrib><creatorcontrib>Krug, Utz</creatorcontrib><creatorcontrib>Berdel, Wolfgang E.</creatorcontrib><creatorcontrib>Woermann, Bernhard J.</creatorcontrib><creatorcontrib>Hiddemann, Wolfgang</creatorcontrib><creatorcontrib>Braess, Jan</creatorcontrib><creatorcontrib>von Bergwelt-Baildon, Michael</creatorcontrib><creatorcontrib>Spiekermann, Karsten</creatorcontrib><creatorcontrib>Herold, Tobias</creatorcontrib><creatorcontrib>Metzeler, Klaus H.</creatorcontrib><title>Validation and refinement of the 2022 European LeukemiaNet genetic risk stratification of acute myeloid leukemia</title><title>Leukemia</title><addtitle>Leukemia</addtitle><addtitle>Leukemia</addtitle><description>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
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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.</description><subject>45/23</subject><subject>692/499</subject><subject>692/699/67/1990/283/1897</subject><subject>692/699/67/69</subject><subject>Acute myeloid leukemia</subject><subject>Cancer Research</subject><subject>Cancer therapies</subject><subject>Chemotherapy</subject><subject>Classification</subject><subject>Clinical trials</subject><subject>Critical Care Medicine</subject><subject>Cytarabine</subject><subject>Genetic markers</subject><subject>Genotypes</subject><subject>Hematology</subject><subject>Intensive</subject><subject>Internal Medicine</subject><subject>Karyotypes</subject><subject>Leukemia</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mutation</subject><subject>Myelodysplastic 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and refinement of the 2022 European LeukemiaNet genetic risk stratification of acute myeloid leukemia</title><author>Rausch, Christian ; Rothenberg-Thurley, Maja ; Dufour, Annika ; Schneider, Stephanie ; Gittinger, Hanna ; Sauerland, Cristina ; Görlich, Dennis ; Krug, Utz ; Berdel, Wolfgang E. ; Woermann, Bernhard J. ; Hiddemann, Wolfgang ; Braess, Jan ; von Bergwelt-Baildon, Michael ; Spiekermann, Karsten ; Herold, Tobias ; Metzeler, Klaus H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c475t-9133420f486853ef73cbb9bd100c967d2ce18ba79d9509a12f9a6de0db371e1b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>45/23</topic><topic>692/499</topic><topic>692/699/67/1990/283/1897</topic><topic>692/699/67/69</topic><topic>Acute myeloid leukemia</topic><topic>Cancer Research</topic><topic>Cancer 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Karsten</au><au>Herold, Tobias</au><au>Metzeler, Klaus H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Validation and refinement of the 2022 European LeukemiaNet genetic risk stratification of acute myeloid leukemia</atitle><jtitle>Leukemia</jtitle><stitle>Leukemia</stitle><addtitle>Leukemia</addtitle><date>2023-06-01</date><risdate>2023</risdate><volume>37</volume><issue>6</issue><spage>1234</spage><epage>1244</epage><pages>1234-1244</pages><issn>0887-6924</issn><eissn>1476-5551</eissn><abstract>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
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| subjects | 45/23 692/499 692/699/67/1990/283/1897 692/699/67/69 Acute myeloid leukemia Cancer Research Cancer therapies Chemotherapy Classification Clinical trials Critical Care Medicine Cytarabine Genetic markers Genotypes Hematology Intensive Internal Medicine Karyotypes Leukemia Medical research Medicine Medicine & Public Health Mutation Myelodysplastic syndrome Oncology p53 Protein Patients Risk Risk groups |
| title | Validation and refinement of the 2022 European LeukemiaNet genetic risk stratification of acute myeloid leukemia |
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