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Chronic Lymphocytic Leukaemia (CLL) is a slow-growing blood cancer where abnormal B-lymphocytes accumulate in the blood, bone marrow, and lymph nodes, impairing immune function. It’s the most common leukaemia in adults, with ~21,000 US cases annually in 2025, median age 70. CLL is often indolent, with some cases never requiring treatment, but can transform to aggressive forms (Richter syndrome, 2-10%). Small lymphocytic lymphoma (SLL) is a similar lymphoma variant.
Many CLL patients are asymptomatic, diagnosed via routine blood tests. When present, symptoms include fatigue, weight loss, frequent infections (from impaired immunity), night sweats, fever, swollen lymph nodes (neck, armpits, groin), enlarged spleen/liver (abdominal fullness), and easy bruising/bleeding. Advanced CLL causes anemia symptoms (pallor, shortness of breath) or thrombocytopenia (petechiae). Symptoms progress slowly over years.
CLL results from genetic mutations causing B-cell overproduction, with no clear cause. Risk factors include age (over 60), family history (5-10% have relatives with CLL), white ethnicity, male gender (1.5:1), and Agent Orange exposure. Mutations (del(17p), TP53, unmutated IGHV) predict aggressive disease. In 2025, epigenetics and microenvironment are key.
Diagnosis uses CBC showing lymphocytosis (>5,000/µL B-cells), flow cytometry confirming clonal B-cells (CD5+, CD23+), and bone marrow biopsy if needed. FISH detects chromosomal abnormalities (del(13q), trisomy 12, del(11q), del(17p)). NGS identifies TP53/IGHV status. Lymph node biopsy differentiates from SLL. In 2025, AI and ctDNA enhance monitoring.
Watchful waiting for asymptomatic CLL; treatment for progressive/symptomatic uses BTK inhibitors (ibrutinib, acalabrutinib), BCL2 inhibitors (venetoclax), or chemoimmunotherapy (FCR for young/fit). Monoclonal antibodies (rituximab, obinutuzumab) combine with targeted agents. SCT for high-risk. In 2025, fixed-duration venetoclax + ibrutinib achieves 90% progression-free survival.
In 2025, CLL survival is 85% 5-year, with many living decades. Targeted therapies improve outcomes, reducing transformation risk. Research on CAR-T and bispecifics could make CLL curable by 2030, with 95% survival.
The information for CLL is drawn from Mayo Clinic’s “Chronic lymphocytic leukemia – Symptoms and causes” for symptoms and causes; PMC’s “Chronic Lymphocytic Leukemia: 2025 Update on the Epidemiology” for epidemiology and outlook; NCI’s “Chronic Lymphocytic Leukemia Treatment (PDQ®)” for treatment; PubMed’s “Chronic Lymphocytic Leukemia: 2025 Update” for 2025 advancements; Hematology Advisor’s “ICML 2025: Progress and Future Directions in CLL Treatment” for future therapies; Cleveland Clinic’s “What Is Chronic Lymphocytic Leukemia (CLL)?” for understanding; ASCO’s “When and How Long to Treat Chronic Lymphocytic Leukemia?” for treatment duration; Lymphoma Action’s “Chronic lymphocytic leukaemia (CLL)” for symptoms; Dana-Farber’s “Chronic Lymphocytic Leukemia (CLL)” for overview; CLL Society’s “What’s New In CLL / SLL” for updates.
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