Recent progress of prognostic biomarkers and risk scoring systems in chronic lymphocytic leukemia
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Recent progress of prognostic biomarkers and risk scoring systems in chronic lymphocytic leukemia Xiaoya Yun1,2,3,4,5, Ya Zhang1,2,3,4,5* and Xin Wang1,2,3,4,5*
Abstract Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia with high heterogeneity in the western world. Thus, investigators identified a number of prognostic biomarkers and scoring systems to guide treatment decisions and validated them in the context of immunochemotherapy. A better understanding of prognostic biomarkers, including serum markers, flow cytometry outcomes, IGHV mutation status, microRNAs, chromosome aberrations and gene mutations, have contributed to prognosis in CLL. Del17p/ TP53 mutation, NOTCH1 mutation, CD49d, IGHV mutation status, complex karyotypes and microRNAs were reported to be of predictive values to guide clinical decisions. Based on the biomarkers above, classic prognostic models, such as the Rai and Binet staging systems, MDACC nomogram, GCLLSG model and CLL-IPI, were developed to improve risk stratification and tailor treatment intensity. Considering the presence of novel agents, many investigators validated the conventional prognostic biomarkers in the setting of novel agents and only TP53 mutation status/del 17p and CD49d expression were reported to be of prognostic value. Whether other prognostic indicators and models can be used in the context of novel agents, further studies are required. Keywords: Chronic lymphocytic leukemia, Prognosis, Prognostic biomarkers, Risk scoring systems
Background Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia in the western world. The disease typically occurs in older patients and presents a variable disease course. The diagnosis of CLL requires the presence of more than 5 × 109/L B lymphocytes in the peripheral blood, sustained at least 3 months. The leukemia cells found by blood smear are characteristically small, mature lymphocytes with a narrow border of cytoplasm and a dense nucleus lacking discernible nucleoli and having partially aggregated chromatin. CLL cells coexpress the surface antigen CD5 together with the B-cell * Correspondence: [email protected]; [email protected]; [email protected] 1 Department of Hematology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong, China Full list of author information is available at the end of the article
antigens CD19, CD20 and CD23 [1]. More than 15,000 newly diagnosed cases and 4500 deaths are currently estimated in the United States [2]. However, only patients with advanced, active and symptomatic disease need therapy. Novel agents, including inhibitors of B-cell receptor signaling pathway (ibrutinib, acalabrutinib, idelalisib and duvelisib) and the inhibitor of the antiapoptotic protein BCL-2 (venetoclax), are superior compared to conventional chemoimmunotherapy (CIT) regimens. Cellular immunotherapy with chimeric antigen receptor T-cell (CAR-T) and allogeneic stem cell transplant (allo-SCT) are available for high-risk
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