{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:16:34Z","timestamp":1785417394170,"version":"3.56.0"},"reference-count":25,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:00:00Z","timestamp":1777248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003074","name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","doi-asserted-by":"crossref","award":["PICT-2021-I-A-00283"],"award-info":[{"award-number":["PICT-2021-I-A-00283"]}],"id":[{"id":"10.13039\/501100003074","id-type":"DOI","asserted-by":"crossref"}]},{"award":["PICT-2021-I-A-00283"],"award-info":[{"award-number":["PICT-2021-I-A-00283"]}],"id":[{"id":"https:\/\/ror.org\/03stxzb56","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017700","name":"Fundaci\u00f3n SALES","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100017700","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Fundaci\u00f3n C\u00e1ncer"},{"name":"Fundaci\u00f3n Pedro Mosoteguy"},{"name":"FUNDALEU"},{"name":"Novartis Argentina"},{"name":"CONICET doctoral fellowship"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Tyrosine kinase inhibitors (TKIs) have transformed chronic myeloid leukemia (CML) into a manageable disease, and discontinuation has become a feasible goal for many patients. However, molecular relapse after TKI cessation remains a challenge. This study investigated factors influencing molecular relapse-free survival (MRFS) in a real-world cohort of CML patients undergoing TKI discontinuation, focusing on clinical, molecular, and immune-related variables. Traditional prognostic tools, such as the Sokal score, showed limited capacity to predict relapse risk in this context. Instead, total treatment duration and depth of molecular response emerged as critical predictors, with longer therapy and deeper remission associated with improved outcomes. A key novel finding was the prognostic relevance of cytokine profiles, particularly interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1). These cytokines were strong predictors of relapse in a decision tree model that achieved high specificity and positive predictive value in an independent validation cohort. Notably, lower IL-6 and MCP-1 levels were associated with increased relapse risk, suggesting reduced immune surveillance may contribute to recurrence. Integrating cytokine signatures with molecular markers improved prognostic accuracy, supporting immune biomarkers as complements to established clinical parameters. These findings underscore the complexity of relapse mechanisms and the need for individualized risk assessment when considering TKI discontinuation.<\/jats:p>","DOI":"10.3390\/cells15090791","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T13:32:22Z","timestamp":1777469542000},"page":"791","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of Predictive Biomarkers Based on Cytokine Profiles for Molecular Relapse After Treatment-Free Remission in Chronic Myeloid Leukemia Patients"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6451-046X","authenticated-orcid":false,"given":"Bianca","family":"Vasconcelos Cordoba","sequence":"first","affiliation":[{"name":"Centro de Investigaciones Oncol\u00f3gicas\u2013Fundaci\u00f3n C\u00e1ncer (CIO-FUCA), Buenos Aires 1426, 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Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.1038\/leu.2016.104","article-title":"European LeukemiaNet Recommendations for the Management and Avoidance of Adverse Events of Treatment in Chronic Myeloid Leukaemia","volume":"30","author":"Steegmann","year":"2016","journal-title":"Leukemia"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1182\/blood-2013-02-483750","article-title":"Safety and Efficacy of Imatinib Cessation for CML Patients with Stable Undetectable Minimal Residual Disease: Results from the TWISTER Study","volume":"122","author":"Ross","year":"2013","journal-title":"Blood"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1016\/S1470-2045(10)70233-3","article-title":"Discontinuation of Imatinib in Patients with Chronic Myeloid Leukaemia Who Have Maintained Complete Molecular Remission for at Least 2 Years: The Prospective, Multicentre Stop Imatinib (STIM) Trial","volume":"11","author":"Bordeaux","year":"2010","journal-title":"Artic. Lancet Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1038\/s41375-025-02664-w","article-title":"2025 European LeukemiaNet Recommendations for the Management of Chronic Myeloid Leukemia","volume":"39","author":"Apperley","year":"2025","journal-title":"Leukemia"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1002\/ajh.26556","article-title":"Tyrosine Kinase Inhibitor Discontinuation in Chronic Myeloid Leukemia: Eligibility Criteria and Predictors of Success","volume":"97","author":"Inzoli","year":"2022","journal-title":"Am. J. Hematol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3657","DOI":"10.1182\/blood-2011-02-335497","article-title":"Leukemic Stem Cell Persistence in Chronic Myeloid Leukemia Patients with Sustained Undetectable Molecular Residual Disease","volume":"118","author":"Chomel","year":"2011","journal-title":"Blood"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1038\/leu.2016.360","article-title":"Increased Proportion of Mature NK Cells Is Associated with Successful Imatinib Discontinuation in Chronic Myeloid Leukemia","volume":"31","author":"Ilander","year":"2017","journal-title":"Leukemia"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.3324\/haematol.2017.165001","article-title":"Natural Killer-Cell Counts Are Associated with Molecular Relapse-Free Survival after Imatinib Discontinuation in Chronic Myeloid Leukemia: The IMMUNOSTIM Study","volume":"102","author":"Rea","year":"2017","journal-title":"Haematologica"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Sanchez, M.B., Vasconcelos Cordoba, B., Pavlovsky, C., Moiraghi, B., Varela, A., Custidiano, R., Fernandez, I., Freitas, M.J., Ventriglia, M.V., and Bendek, G. 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