Chronic Lymphocytic Leukemia (CLL)

Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults in many countries. It usually grows slowly, and many people live for years with good quality of life.

Our team decides with each patient when treatment is truly needed, and uses modern oral targeted medicines and antibody treatments that have transformed CLL care.

About chronic lymphocytic leukemia

What is CLL?

CLL is a cancer of mature-looking but abnormal B-lymphocytes. These cells build up in the blood, bone marrow, lymph nodes and spleen. Over time they can crowd out healthy blood cells and weaken the immune system. A closely related condition, small lymphocytic lymphoma (SLL), involves the same cells mainly in the lymph nodes and is treated the same way.

What are the risk factors for CLL?

• Age — most people are over 60 at diagnosis
• Male sex
• A family history of CLL or other lymphomas
• Exposure to certain herbicides and insecticides

What are the symptoms of CLL?

Many people have no symptoms and CLL is found on a routine blood test. When symptoms occur they may include:

• Painless swollen lymph nodes in the neck, armpit or groin
• Tiredness and reduced exercise tolerance
• Fullness or discomfort under the left ribs (enlarged spleen)
• Fevers, drenching night sweats and unexplained weight loss ("B symptoms")
• Frequent infections, such as chest infections or shingles

How many types of CLL are there?

CLL is grouped by stage (Rai or Binet systems) and by biological markers. Changes such as del(17p)/TP53 mutation and unmutated IGHV predict a more active disease and influence the choice of treatment. Rarely, CLL can change into an aggressive lymphoma — known as Richter's transformation.

CLL is usually diagnosed from a blood sample. Further tests show how advanced it is and which treatment will work best.

Complete blood count and blood smear

A raised lymphocyte count (at least 5,000 B-lymphocytes per microlitre) with typical "smudge cells" on the smear suggests CLL.

Flow cytometry

Testing the blood cells for surface markers (CD5, CD19, CD23 and others) confirms CLL and distinguishes it from other lymphomas.

Genetic and molecular tests

• FISH for del(17p), del(11q), trisomy 12 and del(13q)
• TP53 mutation analysis
• IGHV mutation status

Other tests

• Immunoglobulin levels and tests for hepatitis B and C before treatment
• Coombs test if autoimmune anemia is suspected
• CT scans or ultrasound to measure lymph nodes and spleen when needed
• Bone marrow biopsy or lymph-node biopsy in selected cases, for example if Richter's transformation is suspected

Not everyone with CLL needs treatment straight away. Therapy is started when the disease becomes active — for example with falling blood counts, painful or growing lymph nodes, an enlarged spleen or troublesome symptoms.

CLL treatment is customised according to:

• Stage and symptoms
• Genetic markers (TP53, IGHV)
• Age, other medical conditions and personal preferences

Active monitoring ("watch and wait")

Early-stage CLL without symptoms is followed with regular check-ups and blood tests. Starting treatment early does not improve outcomes in this group.

Targeted therapy

• BTK inhibitors — ibrutinib, acalabrutinib, zanubrutinib (daily tablets)
• BCL-2 inhibitor — venetoclax, often combined with an anti-CD20 antibody for a fixed time
• Anti-CD20 antibodies — obinutuzumab or rituximab

Chemotherapy and chemo-immunotherapy

Older combinations (such as FCR or bendamustine-rituximab) are now used less often but remain options in selected patients.

Bone marrow transplant

An allogeneic stem cell transplant may be considered for younger patients with high-risk CLL that has stopped responding to targeted drugs.

CAR T-cell therapy for Richter's transformation

When CLL transforms into an aggressive lymphoma, intensive treatment, CAR T-cell therapy or transplantation may be used.

Supportive care

Vaccinations, infection prevention, immunoglobulin replacement when needed and regular skin checks are important parts of living well with CLL.

Our adult hematologists follow people with CLL over the long term and decide with them when and how to treat.