Identification of Predictive Biomarkers Based on Cytokine Profiles for Molecular Relapse After Treatment-Free Remission in Chronic Myeloid Leukemia Patients
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.
Authors
- Miguel Arturo Pavlovsky (ORCID: https://orcid.org/0000-0003-4561-3153)
- Ana Inés Varela
- José Mordoh (ORCID: https://orcid.org/0000-0002-8301-9617)
- Maria Del Rosario Custidiano
- Mariana Juni
- Maria Fernanda Tosin
- I Fernández
- Juan Dupont
- Mariano Paoletti
- María José Mela Osorio (ORCID: https://orcid.org/0000-0002-1871-5798)
- Eduardo Bullorsky
- Josefina Freitas
- Georgina Emilia Bendek del Prete
- Bianca Vasconcelos Cordoba
- Carina Gumpel (ORCID: https://orcid.org/0009-0006-3590-6269)
- Etelvina Macchiavello
- Elena Beatriz Moiraghi
- Estrella Mariel Levy (ORCID: https://orcid.org/0000-0003-2954-6667)
- Julio César Sánchez Ávalos
- Federico Sackmann
- Ricardo Khalil Tannuri
- Michele Bianchini (ORCID: https://orcid.org/0000-0003-1142-2295)
- María Cecilia Foncuberta
- Pedro Negri Aranguren
- Isabel Giere
- Verónica Ventriglia
- Ana García de Labanca
- Franco Federico Freilich
- Carolina Pavlovsky
- Marta Catalán
- Romina Mariano (ORCID: https://orcid.org/0009-0009-3545-0427)
- Francisca Rojas
- María Belén Sanchez
- Silvia Miranda
Institutions
- Hospital Británico (UY)
- National University of Mar del Plata (AR)
- National University of General San Martín (AR)
- Hospital Italiano de Buenos Aires (AR)
- National University of Northwestern Buenos Aires (AR)
- Instituto de Investigaciones en Ciencias de la Salud (AR)
- Hospital Ramos Mejía (AR)
- Hospital Provincial de Rosario (AR)
- Hospital Italiano La Plata (AR)
- Hospital de Clínicas "José de San Martín" (AR)
- Instituto Alexander Fleming (AR)
- Fundación para la Investigación, Docencia y Prevención del Cáncer (AR)
- Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno (AR)
- Hospital Posadas (AR)
- Hospital El Cruce (AR)
- Hospital Británico de Buenos Aires (AR)
- Hospital Privado (AR)
- Hospital de Clínicas (UY)
- Instituto Cardiovascular de Buenos Aires (AR)
- Centro Científico Tecnológico Mar del Plata (AR)
Publication Details
- Journal
- Cells
- Published
- 2026-04-27
- DOI
- https://doi.org/10.3390/cells15090791
- Primary Topic
- Chronic Myeloid Leukemia Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Fundación Sales
- Agencia Nacional de Promoción Científica y Tecnológica