Chronic Lymphocytic Leukemia: A Literature Review
Authors
Muhammad Rafi Maulana , Intan Nurmawaddah , Janiya Abdila Ilmiah , Ida Ayu Andara Damayanti , I Made Danuarta Wiguna , Joko Anggoro , Akhada MaulanaDOI:
10.29303/jbt.v25i4.10078Published:
2025-10-01Issue:
Vol. 25 No. 4 (2025): Oktober-DesemberKeywords:
Blood cancer, chronic lymphocytic leukimia, CLL.Articles
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Abstract
Chronic Lymphocytic Leukemia (CLL) is a slowly progressing hematological cancer characterized by the accumulation of abnormal B lymphocytes in the blood, bone marrow, and lymphatic tissue, commonly affecting the elderly. This review aims to comprehensively review the epidemiology, molecular basis of the disease, clinical symptoms, diagnosis, and therapeutic advances of CLL, emphasizing the importance of shifting treatment approaches towards more precision therapy. A literature search was conducted through PubMed, Scopus, and Web of Science using the keywords "Chronic Lymphocytic Leukemia", "epidemiology", "molecular basis of the disease", and "targeted therapy", with publication criteria between 2018–2025, full text, and topic relevance. Analysis was conducted using a narrative review and thematic synthesis approach to identify epidemiological trends, therapeutic effectiveness, and clinical implications. The results showed that the incidence of CLL is higher in Western countries compared to Asia, with a higher prevalence in elderly men. The main genetic factors that play a role include del(13q), del(17p), and TP53 mutations. Over the past decade, targeted therapies such as second-generation Bruton's tyrosine kinase inhibitors (acalabrutinib, zanubrutinib) and the venetoclax-obinutuzumab combination have been shown to improve remission rates with fewer side effects compared to chemoimmunotherapy. Minimal Residual Disease (MRD) status has become an important marker for determining when therapy can be stopped early. In conclusion, this review underscores the crucial role of biomarkers and MRD in modern CLL management. Future developments include the integration of personalized therapy approaches and translational research to develop more effective and safe treatment strategies.
References
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Amin, W. Z., Julyani, S., Bamahry, A., & Natsir, P. (2024). Dosis Kemoterapi Terhadap Perubahan Leukosit Dan Status Gizi. Journal Of Social Science Research, 4, 6470–6482.
Byrd, J. C., Hillmen, P., Ghia, P., Kater, A. P., Chanan-Khan, A., Furman, R. R., O’Brien, S., Nuri Yenerel, M., Illés, A., Kay, N., Garcia-Marco, J. A., Mato, A., Pinilla-Ibarz, J., Seymour, J. F., Lepretre, S., Stilgenbauer, S., Robak, T., Rothbaum, W., Izumi, R., … Jurczak, W. (2021). Acalabrutinib Versus Ibrutinib in Previously Treated Chronic Lymphocytic Leukemia: Results of the First Randomized Phase III Trial. Journal of Clinical Oncology, 39(31), 3441–3452. https://doi.org/10.1200/JCO.21.01210
Eichhorst, B., Niemann, C., & Kater, A. (2023). First-line venetoclax combinations in chroniclymphocytic leukemia. N Engl J Med, 388(19), 1739–1754.
FA, R.-O., & T., H. (2024). Measurable residual disease and outcomes in chroniclymphocytic leukemia: a systematic review and meta-analysis. JAMA Oncol, 10(9), 1220–1231. https://doi.org/doi:10.1001/jamaoncol.2024.2122.
Ghia, P., Pluta, A., Wach, M., Lysak, D., Šimkovič, M., Kriachok, I., Illés, Á., De La Serna, J., Dolan, S., Campbell, P., Musuraca, G., Jacob, A., Avery, E. J., Lee, J. H., Usenko, G., Wang, M. H., Yu, T., & Jurczak, W. (2022). Acalabrutinib Versus Investigator’s Choice in Relapsed/Refractory Chronic Lymphocytic Leukemia: Final ASCEND Trial Results. HemaSphere, 6(12), E801. https://doi.org/10.1097/HS9.0000000000000801
Hallek, M. (2025). Chronic Lymphocytic Leukemia: 2025 Update on the Epidemiology, Pathogenesis, Diagnosis, and Therapy. American Journal of Hematology, 100(3), 450–480. https://doi.org/10.1002/ajh.27546
Junior, H. L. R., Novaes, L. A. C., Datorre, J. G., Moreno, D. A., & Reis, R. M. (2022). Role of Polygenic Risk Score in Cancer Precision Medicine of Non-European Populations: A Systematic Review. Current Oncology, 29(8), 5517–5530. https://doi.org/10.3390/curroncol29080436
JY, L., P, G., & Ghia P. (2022). Epidemiology, pathogenesis, and treatment of chronic lymphocytic leukemia in Asia. Hemasphere, 6(5).
Kater, A. P., Harrup, R., Kipps, T. J., Eichhorst, B., Owen, C. J., Assouline, S., Lamanna, N., Robak, T., de la Serna, J., Jaeger, U., Cartron, G., Montillo, M., Mellink, C., Langerak, A. W., Chyla, B., Popovic, R., Jiang, Y., Millen, R., Lefebure, M., … Seymour, J. F. (2025). The MURANO study: final analysis and retreatment/crossover substudy results of VenR for patients with relapsed/refractory CLL. Blood, 145(23), 2733–2745. https://doi.org/10.1182/blood.2024025525
Kipps, T. J., Stevenson, F. K., Wu, C. J., Croce, C. M., Packham, G., Wierda, W. G., O’Brien, S., Gribben, J., & Rai, K. (2017). Chronic lymphocytic leukaemia. Nature Reviews Disease Primers, 3(January). https://doi.org/10.1038/nrdp.2016.96
Lyon: International Agency for Researchon Cancer. (2024). Cancer Today – Indonesia FactSheet. The Global Cancer Observatory.
M, H., BD, C., D, C., F, C.-C., G, D., & Döhner H. (2018). CLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL. 131(25), 45–60. https://doi.org/doi:10.1182/blood-2017-09-806398.
Mauro, F. R., Starza, I. Della, Messina, M., Reda, G., Trentin, L., Coscia, M., Sportoletti, P., Orsucci, L., Arena, V., Casaluci, G. M., Marasca, R., Murru, R., Laurenti, L., Ilariucci, F., Stelitano, C., Mannina, D., Massaia, M., Rigolin, G. M., Scarfò, L., … Foà, R. (2023). High rate of durable responses with undetectable minimal residual disease with front-line venetoclax and rituximab in young, fit patients with chronic lymphocytic leukemia and an adverse biological profile: results of the GIMEMA phase II LLC1518 – VERITAS study. Haematologica, 108(8), 2091–2100. https://doi.org/10.3324/haematol.2022.282116
Mukamalla, S. K. R., Taneja, A., Malipeddi, D., & Master, S. R. (2023). Chronic Lymphocytic Leukemia. Statpearls Publishing.
Ou, Y., Long, Y., Ji, L., Zhan, Y., Qiao, T., Wang, X., Chen, H., & Cheng, Y. (2022). Trends in Disease Burden of Chronic Lymphocytic Leukemia at the Global, Regional, and National Levels From 1990 to 2019, and Projections Until 2030: A Population-Based Epidemiologic Study. Frontiers in Oncology, 12(March), 1–20. https://doi.org/10.3389/fonc.2022.840616
PDQ® Adult Treatment Editorial Board. (2024). PDQ Chronic Lymphocytic Leukemia Treatment. D: National Cancer Institute.
Puiggros, A., Blanco, G., & Espinet, B. (2014). Genetic abnormalities in chronic lymphocytic leukemia: Where we are and where we go. BioMed Research International, 2014. https://doi.org/10.1155/2014/435983
Samra, Bachar, & Abdul-Hay, M. (2016). Chronic Lymphocytic Leukemia (CLL).
Siegel, R., Miller, K., & Jemal, A. (2020). Cancer Statistics, 2020. Multicenter Study, 70(1), 3–70.
Smith, S. M., Wachter, K., Burris, H. A., Schilsky, R. L., George, D. J., Peterson, D. E., Johnson, M. L., Markham, M. J., Mileham, K. F., Beg, M. S., Bendell, J. C., Dreicer, R., Keedy, V. L., Kimple, R. J., Knoll, M. A., LoConte, N., MacKay, H., Meisel, J. L., Moynihan, T. J., … Uzzo, R. (2021). Clinical Cancer Advances 2021: ASCO’s Report on Progress Against Cancer. Journal of Clinical Oncology, 39(10), 1165–1184. https://doi.org/10.1200/JCO.20.03420
Soleimani, Y., Mahmoudi, S., Daraei, M., Aryanejad, A., Sani, A. H., Khazali, A., Khorsand, S., Mahdavi, M., Sabeti, S., Sadeghi, H., Shahsavari, M. J., Varseh, M., Karamian, S., Mosavi Jarrahi, A., Taherian, M. R., & Jorjani, G. (2025). Chloroform exposure and risk of leukemia: systematic review and meta-analysis. Frontiers in Public Health, 13(April), 1–9. https://doi.org/10.3389/fpubh.2025.1491075
Sun, C., Chen, Y. C., Zurita, A. M., Baptista, M. J., Pittaluga, S., Liu, D., Rosebrock, D., Gohil, S. H., Saba, N. S., Davies-Hill, T., Herman, S. E. M., Getz, G., Pirooznia, M., Wu, C. J., & Wiestner, A. (2023). The immune microenvironment shapes transcriptional and genetic heterogeneity in chronic lymphocytic leukemia. Blood Advances, 7(1), 145–158. https://doi.org/10.1182/bloodadvances.2021006941
Sutarjo, A. S., Wahyudi, D. T., Dachlan, A. S., Mughni, F. A., Suzanna, E., & Sitinjak, D. (2023). Hematological-Related Malignancy-Induced Eosinophilic Dermatosis (He Remained): Sebuah Laporan Kasus Dermatosis Eosinofilik Terkait Leukimia Limfositik Kronis. Media Dermato-Venereologica Indonesiana, 50(2).
The Global Cancer Observatory. (2024). Cancer Today. https://gco.iarc.who.int/media/globocan/factsheets/populations/360-indonesia-fact-sheet.pdf?
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Copyright (c) 2025 Muhammad Rafi Maulana, Intan Nurmawaddah, Janiya Abdila Ilmiah, Ida Ayu Andara Damayanti, I Made Danuarta Wiguna, Joko Anggoro, Akhada Maulana
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