{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T03:16:01Z","timestamp":1771989361513,"version":"3.50.1"},"reference-count":40,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T00:00:00Z","timestamp":1753142400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Daiichi Sankyo Inc.","award":["2016\/0158"],"award-info":[{"award-number":["2016\/0158"]}]},{"name":"Daiichi Sankyo Inc.","award":["2019\/052-1"],"award-info":[{"award-number":["2019\/052-1"]}]},{"name":"Daiichi Sankyo Inc.","award":["PI18\/01340"],"award-info":[{"award-number":["PI18\/01340"]}]},{"name":"Daiichi Sankyo Inc.","award":["PI19\/00730"],"award-info":[{"award-number":["PI19\/00730"]}]},{"name":"Daiichi Sankyo Inc.","award":["FI19\/00059"],"award-info":[{"award-number":["FI19\/00059"]}]},{"name":"Daiichi Sankyo Inc.","award":["CM23\/00148"],"award-info":[{"award-number":["CM23\/00148"]}]},{"name":"Instituto de Investigaci\u00f3n Sanitaria La Fe","award":["2016\/0158"],"award-info":[{"award-number":["2016\/0158"]}]},{"name":"Instituto de Investigaci\u00f3n Sanitaria La Fe","award":["2019\/052-1"],"award-info":[{"award-number":["2019\/052-1"]}]},{"name":"Instituto de Investigaci\u00f3n Sanitaria La Fe","award":["PI18\/01340"],"award-info":[{"award-number":["PI18\/01340"]}]},{"name":"Instituto de Investigaci\u00f3n Sanitaria La Fe","award":["PI19\/00730"],"award-info":[{"award-number":["PI19\/00730"]}]},{"name":"Instituto de Investigaci\u00f3n Sanitaria La Fe","award":["FI19\/00059"],"award-info":[{"award-number":["FI19\/00059"]}]},{"name":"Instituto de Investigaci\u00f3n Sanitaria La Fe","award":["CM23\/00148"],"award-info":[{"award-number":["CM23\/00148"]}]},{"name":"Instituto de Salud Carlos III, 497 Spain","award":["2016\/0158"],"award-info":[{"award-number":["2016\/0158"]}]},{"name":"Instituto de Salud Carlos III, 497 Spain","award":["2019\/052-1"],"award-info":[{"award-number":["2019\/052-1"]}]},{"name":"Instituto de Salud Carlos III, 497 Spain","award":["PI18\/01340"],"award-info":[{"award-number":["PI18\/01340"]}]},{"name":"Instituto de Salud Carlos III, 497 Spain","award":["PI19\/00730"],"award-info":[{"award-number":["PI19\/00730"]}]},{"name":"Instituto de Salud Carlos III, 497 Spain","award":["FI19\/00059"],"award-info":[{"award-number":["FI19\/00059"]}]},{"name":"Instituto de Salud Carlos III, 497 Spain","award":["CM23\/00148"],"award-info":[{"award-number":["CM23\/00148"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: The incidence of cardiac morbimortality in patients with relapsed\/refractory (R\/R) acute myeloid leukemia (AML) is unknown. Methods: We analyze the characteristics, incidence, risk factors, and outcomes of cardiac events in AML patients treated for second-line (2L) or third-line (3L) episodes. Results: Among 327 2L AML patients (median age 62 years old), 135 experienced cardiac events, with an incidence of 38.6% non-fatal and 1.3% fatal events at 6 months. The grade 1\u20132 incidence was 16.8%, and the grade 3\u20134 incidence was 23.5% at 6 months. Overall, 207 cardiac events occurred in the 2L cohort, the most frequent being hypertension (n = 45), bradycardia (n = 39), QTc prolongation (n = 35), heart failure (n = 33), syncope\/presyncope (n = 22), arrhythmia (n = 18), and myocardial ischemia (n = 8). Median OS in the 2L cohort was 9.4 months, 21.4 months in patients with grade 1\u20132, 8.8 months in patients without a cardiac event, 7.6 months in grade 3\u20134 patients, and 2.1 months with in 5 patients (p = 0.0035). The multivariate analysis showed prior cardiologic antecedents (p = 0.013), intensive 2L chemotherapy (p = 0.01), and inclusion in a 2L clinical trial (p &lt; 0.001) as independent risk factors for non-fatal cardiac events. Among 189 patients of the 3L cohort, the incidence of non-fatal and fatal cardiac events was 49.2% and 0% at 6 months, respectively. Non-fatal cardiac events were more frequent in patients with prior cardiac antecedents (p = 0.004). Conclusions: In summary, cardiotoxicity is a frequent and challenging complication in R\/R AML patients. We identified the risk factors that could be relevant to implementing risk-adapted management guidelines, aiming to reduce morbi-mortality in this difficult-to-treat setting.<\/jats:p>","DOI":"10.3390\/cancers17152413","type":"journal-article","created":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T08:45:18Z","timestamp":1753173918000},"page":"2413","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cardiotoxicity in Adult Patients with Relapsed or Refractory Acute Myeloid Leukemia"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-6930-8059","authenticated-orcid":false,"given":"Laura","family":"Torres-Mi\u00f1ana","sequence":"first","affiliation":[{"name":"Hematology Department, Hospital Universitari i Polit\u00e8cnic La Fe, 46026 Val\u00e8ncia, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria La Fe, 46026 Val\u00e8ncia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Blanca","family":"Boluda","sequence":"additional","affiliation":[{"name":"Hematology Department, Hospital Universitari i Polit\u00e8cnic La Fe, 46026 Val\u00e8ncia, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria La Fe, 46026 Val\u00e8ncia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8804-3878","authenticated-orcid":false,"given":"Antonio","family":"Solana-Altabella","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria La Fe, 46026 Val\u00e8ncia, Spain"},{"name":"Pharmacy Department, Hospital Universitari i Polit\u00e8cnic La Fe, 46026 Val\u00e8ncia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2139-8540","authenticated-orcid":false,"given":"Rebeca","family":"Rodr\u00edguez-Veiga","sequence":"additional","affiliation":[{"name":"Hematology Department, Hospital Universitari i Polit\u00e8cnic La Fe, 46026 Val\u00e8ncia, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria La Fe, 46026 Val\u00e8ncia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabel","family":"Cano","sequence":"additional","affiliation":[{"name":"Hematology Department, Hospital Universitari i Polit\u00e8cnic La Fe, 46026 Val\u00e8ncia, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria La Fe, 46026 Val\u00e8ncia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2869-369X","authenticated-orcid":false,"given":"Evelyn","family":"Acu\u00f1a-Cruz","sequence":"additional","affiliation":[{"name":"Hematology Department, Hospital Universitari i Polit\u00e8cnic La Fe, 46026 Val\u00e8ncia, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria La Fe, 46026 Val\u00e8ncia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene","family":"Navarro-Vicente","sequence":"additional","affiliation":[{"name":"Hematology Department, Hospital Universitari i Polit\u00e8cnic La Fe, 46026 Val\u00e8ncia, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria La Fe, 46026 Val\u00e8ncia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6661-9631","authenticated-orcid":false,"given":"Pilar","family":"Lloret-Madrid","sequence":"additional","affiliation":[{"name":"Hematology Department, Hospital Universitari i Polit\u00e8cnic La Fe, 46026 Val\u00e8ncia, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria La Fe, 46026 Val\u00e8ncia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paulina","family":"Hillebrand","sequence":"additional","affiliation":[{"name":"Hematology Department, Hospital Universitari i Polit\u00e8cnic La Fe, 46026 Val\u00e8ncia, 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Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7540-4091","authenticated-orcid":false,"given":"David","family":"Mart\u00ednez-Cuadr\u00f3n","sequence":"additional","affiliation":[{"name":"Hematology Department, Hospital Universitari i Polit\u00e8cnic La Fe, 46026 Val\u00e8ncia, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria La Fe, 46026 Val\u00e8ncia, Spain"},{"name":"CIBERONC CB16\/12\/00284, 46001 Val\u00e8ncia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3275-5593","authenticated-orcid":false,"given":"Pau","family":"Montesinos","sequence":"additional","affiliation":[{"name":"Hematology Department, Hospital Universitari i Polit\u00e8cnic La Fe, 46026 Val\u00e8ncia, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria La Fe, 46026 Val\u00e8ncia, Spain"},{"name":"CIBERONC CB16\/12\/00284, 46001 Val\u00e8ncia, Spain"},{"name":"Department of Medicine, Universitat de Val\u00e8ncia, 46010 Val\u00e8ncia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1179\/1024533214Z.000000000312","article-title":"Acute Myeloid Leukaemia","volume":"19","author":"Hassan","year":"2014","journal-title":"Hematology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1007\/s00277-018-3304-y","article-title":"Salvage Regimens Using Conventional Chemotherapy Agents for Relapsed\/Refractory Adult AML Patients: A Systematic Literature Review","volume":"97","author":"Sanz","year":"2018","journal-title":"Ann. Hematol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1182\/blood-2009-07-235358","article-title":"Diagnosis and Management of Acute Myeloid Leukemia in Adults: Recommendations from an International Expert Panel, on Behalf of the European LeukemiaNet","volume":"115","author":"Estey","year":"2010","journal-title":"Blood"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Konstantinidis, I., Tsokkou, S., Grigoriadis, S., Chrysavgi, L., and Gavriilaki, E. (2024). Cardiotoxicity in Acute Myeloid Leukemia in Adults: A Scoping Study. 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