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Understanding leukemia

Chronic lymphocytic leukemia (CLL)

CLL is one of the most common leukemias in adults in Western countries. It often develops slowly, and many people live with it for years, sometimes without ever needing treatment. This topic explains what CLL is, why a “watch and wait” approach is sometimes chosen, and what modern treatments are available.

Last updated: ~6 min read
Blood smear in chronic lymphocytic leukemia: small lymphocytes with dark round nuclei and scant cytoplasm among red blood cells
Figure 1.Blood smear in CLL: mature-looking but poorly functioning small lymphocytes slowly build up in the blood and lymphatic system.

01Short answer

Chronic lymphocytic leukemia (CLL) is a leukemia in which mature-looking but poorly functioning B lymphocytes slowly build up in the blood, bone marrow, lymph nodes and spleen. It mainly affects older adults: in the US the median age at diagnosis is 71, and it almost never occurs in children. It is often found with no symptoms, when a routine blood test shows raised lymphocytes. Its stage is defined with the Rai or Binet system. In early CLL without symptoms, treatment usually does not start straight away — instead, regular monitoring is used, because early treatment has not been shown to help. When treatment is needed, it mainly uses targeted drugs — BTK inhibitors or venetoclax-based regimens. In the US, 5-year relative survival for CLL is 90.2%.

02Simple explanation

In CLL, the problem is in B lymphocytes — the white blood cells that make antibodies. A “clone” of one B cell slowly multiplies. Under the microscope these cells look mature, but they do not protect well against infections and do not die on time as normal cells do — so they gradually build up.

CLL often causes no symptoms and is found through raised lymphocytes on a blood test done for another reason. Over time, lymph nodes (in the neck, armpits or groin) may swell painlessly, the spleen may enlarge, and tiredness, night sweats, weight loss and frequent infections may appear.

A special feature of CLL: in the early stage without symptoms, treatment usually does not start straight away. This approach is called “watch and wait” (active monitoring). It is not “doing nothing” — it means closely tracking the disease with regular check-ups and blood tests. Research has shown that early treatment at this stage does not help people live longer.

Treatment starts when symptoms appear or blood counts worsen. Today the main treatments are targeted drugs: BTK inhibitors (e.g. ibrutinib, acalabrutinib, zanubrutinib) and venetoclax (often combined with an antibody). Chemotherapy is used less often than before.

CLL can weaken the immune system, so preventing infection matters — vaccines (non-live), good hygiene and seeing a doctor quickly if you have a fever. The NHS notes that people can often live with CLL for many years.

03Scientific explanation

Diagnosis is usually made by finding ≥5,000/µL clonal B lymphocytes in the blood with a characteristic immunophenotype (CD5- and CD23-positive B cells) on flow cytometry; a bone marrow biopsy is often not needed. When clonal B cells are below 5,000/µL and there are no other features, the condition is called monoclonal B-cell lymphocytosis (MBL); according to the NCI, sensitive tests find MBL in 3% of adults over 40 and 6% of adults over 60. When the same disease is mainly in the lymph nodes, it is called small lymphocytic lymphoma (SLL).

The Rai system (0–IV) takes into account lymphocytosis, enlarged lymph nodes, spleen/liver, anemia and thrombocytopenia; the Binet system (A, B, C) is based on the number of enlarged lymphoid areas and on anemia/thrombocytopenia. Prognostic markers include IGHV mutation status (mutated is more favourable), del(13q) on FISH (favourable when isolated), trisomy 12, del(11q) and del(17p)/TP53 mutation (high risk, poor response to chemotherapy). These markers influence the choice of treatment: with TP53 disruption, chemotherapy is avoided.

Reasons to start treatment (based on iwCLL criteria) include symptomatic or progressive disease: worsening marrow failure (anemia, thrombocytopenia), large or symptomatic spleen/lymph nodes, rapidly rising lymphocytosis, B symptoms (fever, night sweats, weight loss) and autoimmune cytopenias that do not respond to steroids. For symptomatic CLL, the NCI lists BTK inhibitors (acalabrutinib, zanubrutinib, ibrutinib), venetoclax with obinutuzumab or rituximab, chemoimmunotherapy and other options. Venetoclax-obinutuzumab is a fixed-duration treatment (about 1 year), whereas BTK inhibitors are usually taken continuously. The non-covalent BTK inhibitor pirtobrutinib can be used after a previous BTK inhibitor.

Complications include hypogammaglobulinemia and bacterial/viral infections (the NCI notes shingles as a frequent infection), autoimmune hemolytic anemia and immune thrombocytopenia, second cancers (especially skin cancers) and, rarely, Richter transformation — CLL turning into an aggressive lymphoma (usually diffuse large B-cell lymphoma). Sudden fever, heavy night sweats, rapid weight loss or fast-growing lymph nodes call for prompt assessment for transformation. In the US, 5-year relative survival is 90.2% (SEER, 2016–2022).

04What happens in the body?

Where do the cells build up?

CLL cells gather in the blood, marrow, lymph nodes and spleen. Lymph nodes usually swell painlessly. When the spleen enlarges, you may feel fullness under the left ribs. The stage is defined from these findings and the blood counts.

Close-up of a translucent torso: softly glowing teal lymph nodes in the neck, armpits and groin, and a slightly enlarged spleen with a warm glow under the left ribs.
Figure 2.CLL cells can gather in the lymph nodes and spleen and make them larger.

Why do genetic markers matter?

IGHV mutation status, FISH (del(13q), trisomy 12, del(11q), del(17p)) and TP53 testing help predict how the disease will behave and which treatment is most suitable. These tests are usually repeated before treatment starts, because they can change over time.

“Watch and wait” — a smart strategy

In CLL without symptoms, regular check-ups are done — usually a blood test and examination every few months. This can feel unsettling, but the aim is to spare you unnecessary side effects. Tell your team about any new symptoms during this time.

Beside a translucent human silhouette on a dark navy background, a delicate glowing outline of a round clock and calm, wavy lines of blood; the mood is calm and hopeful.
Figure 3.“Watch and wait”: in early CLL, regular monitoring can be as important as treatment.

Modern targeted treatment

BTK inhibitors block the growth signal of B cells, while venetoclax restarts the self-destruct programme (apoptosis) in leukemia cells. The choice depends on age, other conditions, genetic markers and your preferences (continuous or fixed-duration treatment).

05CLL: a slow but closely watched path

How CLL progresses and is managed, in four steps.

A clonal B cell — A clone of one B lymphocyte slowly multiplies.1A clonal B cellA clone of one B lymphocyte slowly multiplies.
Slow build-up — The cells do not die on time and accumulate.2Slow build-upThe cells do not die on time and accumulate.
Nodes and spleen — Lymph nodes and the spleen may enlarge.3Nodes and spleenLymph nodes and the spleen may enlarge.
Monitor or treat — Symptoms and blood counts guide the decision.4Monitor or treatSymptoms and blood counts guide the decision.
Active monitoringRegular check-ups in the early stage.
Targeted treatmentBTK inhibitors or venetoclax.
Infection protectionVaccines and seeking help early.

06Rai stages of CLL (simplified)

Rai stageWhat is found?Risk group
0Only raised lymphocytes in the bloodLow
ILymphocytosis + enlarged lymph nodesIntermediate
IILymphocytosis + enlarged spleen and/or liver (nodes may be enlarged)Intermediate
IIILymphocytosis + anemiaHigh
IVLymphocytosis + low plateletsHigh

* The Rai stage gives a general picture of how the disease may behave, but treatment decisions also rely on symptoms, genetic markers and how blood counts change over time. Anemia or low platelets can have an autoimmune cause rather than CLL itself — your doctor will tell these apart.

07Key terms

CLL
Chronic lymphocytic leukemia — a leukemia in which clonal B lymphocytes slowly build up.
SLL
Small lymphocytic lymphoma — the same disease, mainly in the lymph nodes.
MBL
Monoclonal B-cell lymphocytosis — a small number of clonal B cells, usually without symptoms.
Lymphocytosis
More lymphocytes in the blood than normal.
Rai / Binet
Two systems for staging CLL.
IGHV
The immunoglobulin heavy-chain gene; its mutation status affects outlook.
del(17p) / TP53
High-risk genetic changes.
BTK inhibitor
A targeted drug that blocks the growth signal of B cells.
Venetoclax
A drug that blocks the BCL2 protein and restores apoptosis.
Richter transformation
CLL turning into an aggressive lymphoma (rare).

08Key points

  • CLL is a leukemia in which clonal B lymphocytes slowly build up.
  • It mainly affects older adults and is often found on a routine blood test.
  • In the early stage without symptoms, “watch and wait” is usually chosen.
  • Treatment starts when symptoms appear or blood counts worsen.
  • The main treatments are BTK inhibitors and venetoclax-based regimens.
  • Markers such as IGHV and TP53 influence the choice of treatment.
  • Protection from infection and vaccination are important.
  • In the US, 5-year survival is about 90%; many people live with CLL for years.

09Frequently asked questions

I have leukemia, but they are not treating it. Isn’t that dangerous?

In early CLL without symptoms, research has shown that immediate treatment does not help people live longer but can cause side effects. During monitoring, your doctor checks on you regularly and starts treatment in good time if it becomes necessary. Talk openly about your worries.

What should I watch for during monitoring?

New or growing lymph nodes, unexplained fever, heavy night sweats, weight loss, increasing tiredness, bruising and frequent infections. If any of these appear, tell your team without waiting for your next appointment.

Which vaccines can I have?

Non-live vaccines (for example flu, pneumococcal and COVID-19) are usually recommended, while live vaccines often need to be avoided. Check with your hematologist which vaccines suit you and when.

Can CLL be cured?

CLL is usually regarded as a chronic disease: modern treatments can keep it under control for a long time, but a complete cure is not usually expected. Many people live full lives with it for many years.

How do I choose between continuous and fixed-duration treatment?

BTK inhibitors are usually taken continuously for as long as they work; venetoclax-obinutuzumab lasts about a year, followed by a treatment-free period. The choice depends on genetic markers, other conditions, side-effect risks and your preferences.

If someone in my family has CLL, will I get it too?

Close relatives of people with CLL have a somewhat higher risk, but the absolute risk is still low, and most relatives never develop CLL. Routine screening of healthy relatives is not currently recommended.

10Questions for your doctor

Take these questions to your appointment. The ones you save are collected on the “My questions” page and stay on this device only.

  1. What stage is my CLL?

  2. Do I need treatment yet, or is monitoring enough?

  3. What are my IGHV status and TP53 result?

  4. Which signs would show it is time to start treatment?

My questions

12Sources

  1. National Cancer Institute (NCI). Chronic Lymphocytic Leukemia Treatment (PDQ®) — Patient Version
  2. National Cancer Institute (NCI). Chronic Lymphocytic Leukemia Treatment (PDQ®) — Health Professional Version
  3. National Cancer Institute (NCI), SEER. Cancer Stat Facts: Chronic Lymphocytic Leukemia (CLL)
  4. American Cancer Society. What Is Chronic Lymphocytic Leukemia?
  5. American Cancer Society. Chronic Lymphocytic Leukemia Stages
  6. NHS. Chronic lymphocytic leukaemia — Symptoms
  7. NHS. Chronic lymphocytic leukaemia — Treatment
  8. Blood (American Society of Hematology) — iwCLL, via PMC. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia (International Workshop on CLL)
  9. National Cancer Institute (NCI). Venetoclax — Cancer Drug Information
  10. National Cancer Institute (NCI). Targeted Therapy to Treat Cancer
  11. Leukemia (Nature) — WHO 5th edition. WHO Classification of Haematolymphoid Tumours: Lymphoid Neoplasms
  12. National Cancer Institute (NCI). NCI Dictionary of Cancer Terms: lymphatic system
Medical disclaimerThis information is for educational purposes only and does not replace medical advice.
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