Association of Cytogenetics Aberrations and IGHV Mutations with Outcome in Chronic Lymphocytic Leukemia Patients in a Real-World Clinical Setting

• Published in: Global medical genetics Vol. 11; no. 1; pp. 59 - 68
• Main Authors: Muñoz-Novas, Carolina, González-Gascón-Y-Marín, Isabel, Figueroa, Iñigo, Sánchez-Paz, Laura, Pérez-Carretero, Claudia, Quijada-Álamo, Miguel, Rodríguez-Vicente, Ana-Eugenia, Infante, María-Stefania, Foncillas, María-Ángeles, Landete, Elena, Churruca, Juan, Marín, Karen, Ramos, Victoria, Sánchez Salto, Alejandro, Hernández-Rivas, José-Ángel
• Format: Journal Article
• Language: English
• Published: Germany Georg Thieme Verlag KG 01.01.2024
• Subjects: chronic lymphocytic leukemia; complex karyotype; IGHV mutation status; Original; overall survival; time to first treatment; overall survival; IGHV mutation status; chronic lymphocytic leukemia; complex karyotype; time to first treatment
• ISSN: 2699-9404; 2699-9404
• DOI: 10.1055/s-0044-1779668

Immunoglobulin heavy chain variable ( ) region mutations, mutation, fluorescence in situ hybridization (FISH), and cytogenetic analysis are the most important prognostic biomarkers used in chronic lymphocytic leukemia (CLL) patients in our daily practice. In real-life environment, there are scarce studies that analyze the correlation of these factors with outcome, mainly referred to time to first treatment (TTFT) and overall survival (OS). This study aimed to typify mutation status, family usage, FISH aberrations, and complex karyotype (CK) and to analyze the prognostic impact in TTFT and OS in retrospective study of 375 CLL patients from a Spanish cohort. We found unmutated CLL (U-CLL) was associated with more aggressive disease, shorter TTFT (48 vs. 133 months,  < 0.0001), and shorter OS (112 vs. 246 months,  < 0.0001) than the mutated CLL. was the most frequently used family (46%), followed by (30%) and (16%). and subfamilies were associated with poor prognosis, while and showed the best outcomes. The prevalence of CK was 15% and was significantly associated with U-CLL. In the multivariable analysis, gene usage and del13q were associated with longer TTFT, while VH1-02, +12, del11q, del17p, and U-CLL with shorter TTFT. Moreover, VH1-69 usage, del11q, del17p, and U-CLL were significantly associated with shorter OS. A comprehensive analysis of genetic prognostic factors provides a more precise information on the outcome of CLL patients. In addition to FISH cytogenetic aberrations, and mutations, gene families, and CK information could help clinicians in the decision-making process.