{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T10:52:24Z","timestamp":1782039144253,"version":"3.54.5"},"reference-count":34,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:00:00Z","timestamp":1761696000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Acute myeloid leukemia (AML) in elderly patients presents a major therapeutic challenge, as many are deemed unfit for intensive chemotherapy due to age, comorbidities, or frailty. Venetoclax in combination with hypomethylating agents (HMA) has emerged as a standard\u2010of\u2010care for this population, yet outcomes remain heterogeneous and predictive tools are limited. In this retrospective single\u2010center study, we analyzed 52 treatment\u2010na\u00efve AML patients receiving venetoclax combined with either azacitidine (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200933) or decitabine (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200919) at the Hematology Department of Cosenza Hospital between August 2021 and June 2025. Frailty was assessed using the Clinical Frailty Scale (CSHA CFS), with 19 patients classified as low frailty (score \u2264\u20093) and 33 as high frailty (score &gt;\u20093). The median age was 75.3\u2009years (range 58.2\u201389.2), and the cohort included 33 de novo and 19 secondary AML cases. After a median follow\u2010up of 18\u2009months, 34 patients (65.4%) had died: 14 due to disease progression, 12 due to treatment\u2010related toxicity\u2014predominantly severe infections\u2014and 5 from unrelated causes. ROC curve analysis showed that a CFS score &gt;\u20093 was associated with worse survival (AUC 0.75, 95% CI 0.61\u20130.89,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.004), with median overall survival of 7.6\u2009months for low\u2010frailty patients versus 2.5\u2009months for high\u2010frailty patients (1\u2010year OS 44.1% vs. 18.7%,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.031). Multivariate analysis confirmed that lower frailty (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.031) and azacitidine\u2010based therapy (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.025) were independently associated with improved survival. Overall response rate was 48%, including 21 complete responses (CR\/CRi) and 4 partial responses. Frailty was the only significant predictor of response (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.005), whereas age, sex, type of AML, ELN risk score, renal function, BMI, or type of HMA did not significantly influence outcomes. Grade 3\u20134 treatment\u2010related adverse events occurred in all patients, predominantly hematological; non\u2010hematological events included infections (61.9%), cardiotoxicity (11.9%), and liver toxicity (9.5%). High\u2010frailty patients experienced a higher incidence of infections (72.7% vs. 36.8%,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.02) and hospitalizations (57.6% vs. 21.1%,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.011). These results suggest that the CSHA CFS is a simple and clinically meaningful tool to stratify elderly AML patients for venetoclax\u2013HMA therapy, identifying those at higher risk of treatment\u2010related complications and poor survival. Incorporating frailty assessment into routine practice may enhance patient selection, optimize supportive care, and guide individualized therapeutic decisions. Prospective, multicenter studies are warranted to validate these findings and refine the use of frailty\u2010guided treatment strategies in this vulnerable population.\n                  <\/jats:p>","DOI":"10.1111\/ejh.70058","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T18:24:21Z","timestamp":1761762261000},"page":"160-168","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Clinical Utility of Frailty Scoring in Elderly Acute Myeloid Leukemia Patients Treated With Venetoclax and Hypomethylating Agents"],"prefix":"10.1111","volume":"116","author":[{"given":"Ernesto","family":"Vigna","sequence":"first","affiliation":[{"name":"Hematology Unit, Department of Onco\u2010Hematology AO of Cosenza  Cosenza Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9456-2404","authenticated-orcid":false,"given":"Antonella","family":"Bruzzese","sequence":"additional","affiliation":[{"name":"Hematology Unit, Department of Onco\u2010Hematology AO of Cosenza  Cosenza Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrica Antonia","family":"Martino","sequence":"additional","affiliation":[{"name":"Hematology Unit, Department of Onco\u2010Hematology AO of Cosenza  Cosenza Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Corsonello","sequence":"additional","affiliation":[{"name":"Unit of Geriatric Medicine Italian National Research Center on Aging (IRCCS INRCA)  Cosenza Italy"},{"name":"Department of Pharmacy, Health and Nutritional Science University of Calabria  Rende Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santino","family":"Caserta","sequence":"additional","affiliation":[{"name":"Hematology Unit, Department of Onco\u2010Hematology AO of Cosenza  Cosenza Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Labanca","sequence":"additional","affiliation":[{"name":"Hematology Unit, Department of Onco\u2010Hematology AO of Cosenza  Cosenza Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Mendicino","sequence":"additional","affiliation":[{"name":"Hematology Unit, Department of Onco\u2010Hematology AO of Cosenza  Cosenza Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenio","family":"Lucia","sequence":"additional","affiliation":[{"name":"Hematology Unit, Department of Onco\u2010Hematology AO of Cosenza  Cosenza Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia","family":"Olivito","sequence":"additional","affiliation":[{"name":"Hematology Unit, Department of Onco\u2010Hematology AO of Cosenza  Cosenza Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Amodio","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine University of Catanzaro  Catanzaro Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fortunato","family":"Morabito","sequence":"additional","affiliation":[{"name":"AIL Sezione di Cosenza  Cosenza Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5256-0726","authenticated-orcid":false,"given":"Massimo","family":"Gentile","sequence":"additional","affiliation":[{"name":"Hematology Unit, Department of Onco\u2010Hematology AO of Cosenza  Cosenza Italy"},{"name":"Department of Pharmacy, Health and Nutritional 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