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However, predictors of outcome are elusive. The objective of the current retrospective observational multicenter study of 240 adult patients (median age 68.6 years) with R\/R AML was to establish a prognostic risk score. Overall response was documented in 106 (44%) patients. With a median follow-up of 31.5 months, 179 deaths were recorded. Median overall survival (mOS) was 7.9 months. In multivariate analysis of the subgroup with molecular information (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009174), risk factors for inferior survival included the presence of extramedullary disease, HMA pretreatment and mutations in\n                    <jats:italic>NF1<\/jats:italic>\n                    ,\n                    <jats:italic>PTPN11<\/jats:italic>\n                    ,\n                    <jats:italic>FLT3<\/jats:italic>\n                    , and\n                    <jats:italic>TP53<\/jats:italic>\n                    , whereas mutated\n                    <jats:italic>SF3B1<\/jats:italic>\n                    was identified as favorable risk factor. These risk factors were subsequently applied to construct an HR-weighted risk model that allocated patients to one of three risk groups with significantly different survival outcomes: favorable (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200946; mOS 21.4 months), intermediate (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200975; mOS 7.5 months), and adverse (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200953; mOS 4.6 months;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). The model was validated in 189 AML patients treated with HMA\/VEN in first line. This clinical-molecular, 3-tiered\n                    <jats:bold>ven<\/jats:bold>\n                    etoclax\n                    <jats:bold>p<\/jats:bold>\n                    rognostic\n                    <jats:bold>r<\/jats:bold>\n                    isk\n                    <jats:bold>s<\/jats:bold>\n                    core (VEN-PRS) for HMA\/VEN treatment outcomes in R\/R AML patients will support the selection of appropriate treatment options in this high-risk population.\n                  <\/jats:p>","DOI":"10.1038\/s41375-024-02501-6","type":"journal-article","created":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T08:15:32Z","timestamp":1736324132000},"page":"614-622","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["A novel prognostic risk model for patients with refractory\/relapsed acute myeloid leukemia receiving venetoclax plus hypomethylating agents"],"prefix":"10.1038","volume":"39","author":[{"given":"Rabia","family":"Shahswar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Razif","family":"Gabdoulline","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Krueger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Wichmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina S.","family":"G\u00f6tze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krischan","family":"Braitsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9038-3265","authenticated-orcid":false,"given":"Manja","family":"Meggendorfer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6080-6175","authenticated-orcid":false,"given":"Laura","family":"Schmalbrock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5890-5510","authenticated-orcid":false,"given":"Lars","family":"Bullinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5897-3310","authenticated-orcid":false,"given":"Franziska","family":"Modemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Fiedler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juergen","family":"Krauter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Kaun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Rotermund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9647-5024","authenticated-orcid":false,"given":"Andreas","family":"Vo\u00df","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne Lisa","family":"Behrens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1367-2725","authenticated-orcid":false,"given":"Anke Katharina","family":"Bergmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Koller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6758-6104","authenticated-orcid":false,"given":"Gernot","family":"Beutel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5848-6152","authenticated-orcid":false,"given":"Felicitas","family":"Thol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2438-1955","authenticated-orcid":false,"given":"Florian","family":"Heidel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5318-9044","authenticated-orcid":false,"given":"Michael","family":"Heuser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,8]]},"reference":[{"key":"2501_CR1","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1182\/blood.2023022481","volume":"143","author":"F Thol","year":"2024","unstructured":"Thol F, D\u00f6hner H, Ganser A. 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Cancer Discov. 2019;9:910\u201325.","journal-title":"Cancer Discov"}],"container-title":["Leukemia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41375-024-02501-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41375-024-02501-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41375-024-02501-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T11:08:01Z","timestamp":1741086481000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41375-024-02501-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,8]]},"references-count":37,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,3]]}},"alternative-id":["2501"],"URL":"https:\/\/doi.org\/10.1038\/s41375-024-02501-6","relation":{},"ISSN":["0887-6924","1476-5551"],"issn-type":[{"value":"0887-6924","type":"print"},{"value":"1476-5551","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,8]]},"assertion":[{"value":"14 May 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 November 2024","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 December 2024","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 January 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"MH declares honoraria from Abbvie, Eurocept, Jazz Pharmaceuticals, Janssen, Novartis, Takeda, paid consultancy for Abbvie, Agios, BMS, Daiichi Sankyo, Glycostem, Jazz Pharmaceuticals, Kura Oncology, Novartis, Pfizer, PinotBio, Roche, Tolremo, and research funding to his institution from Abbvie, Agios, Astellas, Bayer Pharma AG, BergenBio, Daiichi Sankyo, Glycostem, Jazz Pharmaceuticals, Loxo Oncology, Novartis, Pfizer, PinotBio, Roche. RS declares support for meeting attendance from AbbVie. EK declares honoraria and\/or travel support from Abbvie, JAZZ, BMS, Otsuka, Servier. WF declares honoraria from Jazz Pharmaceuticals, Pfizer, Amgen, Abbvie, Celgene, MorphoSys, Ariad\/Incyte, Stemline Therapeutics, Clinigen, Daiichi Sankyo, Otsuka and Servier outside the submitted work; in addition, research support from Apis; patent issued with Amgen; support for medical writing for Amgen, Pfizer, and AbbVie. KSG declares honoraria from BMS and Abbvie. FM declares support for meeting attendance from Servier, AbbVie, Incyte, Gilead, Jazz Pharmaceuticals, Novartis, Teva, Pfizer, and Amgen, support for medical writing from Servier, and Springer Verlag, research support from Apis Technologies, and Daiichi Sankyo, honoraria from Servier, Jazz Pharmaceuticals, and AbbVie. The other authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The registry was approved by the local Ethics Review Committee (ethical vote No.7972_BO_K_2018).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"All patients had given written informed consent to the off-label use of venetoclax, genetic analysis and use of clinical data according to the Declaration of Helsinki and institutional guidelines.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}