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Diagnosis and tests

CLL: symptoms, diagnosis and staging

Chronic lymphocytic leukemia is one of the most common leukemias in adults, and it often causes no symptoms at all — it is found because of a raised lymphocyte count on a routine blood test. This topic covers the signs of CLL, which situations are urgent, how the diagnosis is made, what the stages mean and why many people do not start treatment straight away.

Last updated: ~8 min read
Calmly flowing blood on a dark navy background; many small round lymphocytes with a cool blue glow are spread evenly among red disc-shaped red cells.
Figure 1.Concept: in CLL, small, mature-looking B lymphocytes slowly build up in the blood.

01Short answer

In CLL, B lymphocytes that look mature but do not work properly slowly build up in the bone marrow, blood and lymph nodes. Often there are no symptoms. When there are: painless swollen lymph nodes, tiredness, night sweats, fever, weight loss, frequent infections and a heavy feeling under the left ribs. A high fever with signs of infection, yellow skin and dark urine, sudden bleeding or rapidly growing lymph nodes need prompt attention. The diagnosis is made with a blood count (≥5×10⁹/L clonal B lymphocytes in the blood) and flow cytometry (CD5, CD19, weak CD20, CD23, CD200); a bone marrow test is usually not needed. The stage is set with the Rai or Binet system; before treatment, TP53/del(17p) and IGHV tests are done. In early stages, “watch and wait” is often chosen. Discuss your results with your hematologist.

02Simple explanation

In CLL, one type of lymphocyte — the B lymphocyte — does not die off when it should and slowly builds up. Under the microscope these cells look like ordinary mature lymphocytes, but they are poor at fighting infection. They gather in the blood, bone marrow, lymph nodes and spleen.

Because the disease develops very slowly, many people have no symptoms at all. CLL is often found when a blood test done for another reason shows raised lymphocytes. Some of these people live for years without treatment, with regular monitoring only.

When symptoms occur, they can include: painless swollen lymph nodes in the neck, armpits or groin; tiredness; night sweats, unexplained fever and weight loss (doctors call these B symptoms); frequent or lingering infections; and a heavy feeling under the left ribs with early fullness (an enlarged spleen). As the disease progresses, anemia and low platelets can develop.

In CLL, the immune system sometimes mistakenly attacks the body’s own blood cells. This can cause sudden autoimmune anemia (tiredness, breathlessness, yellow skin, dark urine) or a drop in platelets (bruising, petechiae). Such signs need prompt assessment.

The diagnosis is usually made with simple blood tests: a blood count, a smear and flow cytometry on blood. The doctor then examines the lymph nodes, liver and spleen and, together with the blood results, sets the stage. If treatment becomes necessary, further genetic tests help choose the drug.

03Scientific explanation

Under the iwCLL 2018 criteria, diagnosis requires ≥5×10⁹/L clonal B lymphocytes in the blood, sustained for at least 3 months. Clonality is confirmed on flow cytometry by the presence of only one light chain (kappa or lambda). The typical immunophenotype is CD5, CD19, CD23 and CD200 positive, with weak CD20, CD79b and surface immunoglobulin, and CD10 and FMC7 usually negative. This profile helps distinguish CLL from other B-cell lymphomas, especially mantle cell lymphoma (usually CD23 negative, cyclin D1 positive, t(11;14)). The smear shows small mature lymphocytes and typical “smudge” (Gumprecht) cells.

If clonal B cells are below 5×10⁹/L and there are no enlarged nodes or organs and no cytopenias, the condition is called monoclonal B lymphocytosis (MBL) — not leukemia but a precursor state that needs monitoring. If blood lymphocytes are low but lymph nodes or the spleen are enlarged, it is small lymphocytic lymphoma (SLL) — another form of the same disease as CLL — usually confirmed with a lymph node biopsy. A bone marrow test is usually not needed for diagnosis; it is done for unexplained cytopenias or sometimes before treatment.

Staging is based on examination and the blood count. Rai: 0 — lymphocytosis only; I — enlarged lymph nodes; II — enlarged spleen or liver; III — hemoglobin <11 g/dL; IV — platelets <100×10⁹/L (in the modern modification 0 is low, I–II intermediate and III–IV high risk). Binet: A — fewer than three enlarged lymphoid areas; B — three or more; C — hemoglobin <10 g/dL or platelets <100×10⁹/L. Anemia and thrombocytopenia can also be autoimmune, in which case the stage is interpreted differently, so a direct antiglobulin (Coombs) test, reticulocytes and haptoglobin are checked.

Prognostic and pre-treatment tests: FISH for del(17p), del(11q), trisomy 12 and del(13q); TP53 mutation; IGHV mutation status (unmutated IGHV is linked to a more active course); β2-microglobulin; and sometimes a complex karyotype. These are combined in the CLL-IPI (TP53 status, IGHV, β2-microglobulin >3.5 mg/L, clinical stage, age >65), which gives four risk groups. The TP53/del(17p) test is repeated before treatment starts, because the result can change over time and directly affects the choice of drug. Immunoglobulin levels (antibody deficiency) are also checked, along with hepatitis B/C and HIV screening. A CT scan is not routinely needed in early-stage disease.

04What happens in the body?

When to seek help quickly or urgently

Contact your doctor straight away or call emergency services if: you have a temperature of 38 °C or higher, shivering, a cough, breathlessness or other signs of a serious infection (antibodies can be low in CLL); your skin or eyes turn yellow, your urine darkens, or you suddenly feel very tired and breathless (autoimmune anemia); many bruises, petechiae or bleeding appear suddenly; one or more lymph nodes grow quickly over weeks, especially with fever, heavy sweating and weight loss (possible Richter transformation). If a painful blistering rash appears on your body (shingles), see a doctor promptly.

In what order are the tests done?

Usually: a blood count (often by chance) → blood smear → flow cytometry on blood (clonality and CLL phenotype) → examination of lymph nodes, liver and spleen → stage (Rai or Binet) → further tests: Coombs test, reticulocytes, immunoglobulins, β2-microglobulin, hepatitis screening → FISH, TP53 and IGHV when treatment is needed. A lymph node biopsy or bone marrow test is needed only in particular situations.

In a translucent human torso silhouette, the lymph nodes of the neck, armpits and groin and the spleen glow a soft teal and gold, linked by thin lymph vessels.
Figure 2.The stage is set by the state of the lymph nodes, the spleen and the blood counts.

What do the results roughly mean?

A typical CLL profile on flow cytometry confirms the diagnosis. The stage shows how far the disease has spread in the body and how it affects the blood counts. TP53/del(17p) and IGHV status help predict the future course and which drugs will suit best. These results decide not when to treat, but how.

What does “watch and wait” mean?

In early-stage disease without symptoms, starting treatment straight away does not help people live longer. So doctors offer “active monitoring” with regular check-ups and blood tests. Treatment starts only when the disease becomes “active”: for example, when anemia or low platelets deepen, the spleen or lymph nodes grow a lot, or troublesome B symptoms appear. It is not “doing nothing” — it is planned monitoring.

A calm horizontal path of light on a dark background; small bright points sit along it at even intervals, with a soft warm dawn in the distance.
Figure 3.“Watch and wait”: planned monitoring in early disease — treatment starts when it is needed.

Questions you can ask your doctor

Do I have CLL, SLL or MBL? What is my stage (Rai/Binet)? Do I need treatment now, or monitoring? Which signs would be a reason to start treatment? How often should I have blood tests? What are my TP53, del(17p) and IGHV results, or when will they be checked? Which vaccinations are recommended for me? Whom do I contact if I have signs of infection?

Living with waiting

Being told you have leukemia and then sent home without treatment can feel strange and worrying. Some people call it “watch and worry”. Asking questions openly, knowing the monitoring plan clearly, a healthy lifestyle, vaccinations and support groups all make this period easier. Many people with CLL live full lives for many years.

05CLL: from blood count to plan

The diagnosis and plan in CLL usually take shape in four steps.

Blood count — Lymphocytosis; ≥5×10⁹/L clonal B cells.1Blood countLymphocytosis; ≥5×10⁹/L clonal B cells.
Flow cytometry — CD5, CD19, CD23, CD200; a single light chain.2Flow cytometryCD5, CD19, CD23, CD200; a single light chain.
Examination and stage — Lymph nodes, spleen, blood counts: Rai / Binet.3Examination and stageLymph nodes, spleen, blood counts: Rai / Binet.
Prognostic tests — TP53/del(17p), IGHV, β2-microglobulin.4Prognostic testsTP53/del(17p), IGHV, β2-microglobulin.
Watch and waitIn early disease without symptoms.
TreatmentWhen the disease becomes active, tailored to its profile.
Infection protectionVaccinations and prompt contact.

06Stages of CLL (Rai and Binet, simplified)

RiskRai / BinetFindings
LowRai 0 / Binet ALymphocytosis only, or fewer than three enlarged lymphoid areas; normal hemoglobin and platelets
IntermediateRai I–II / Binet BEnlarged lymph nodes, spleen or liver; three or more areas in Binet B
HighRai III–IV / Binet CAnemia (Rai: Hb <11, Binet: <10 g/dL) or platelets <100×10⁹/L

* The stage alone is not a reason to start treatment — the iwCLL “active disease” criteria are used. Autoimmune anemia or thrombocytopenia is assessed separately. Discuss your own results with your hematologist.

07Key terms

B lymphocyte
An antibody-making white blood cell; CLL arises from these cells.
Lymphocytosis
A raised number of lymphocytes in the blood.
MBL
Monoclonal B lymphocytosis — fewer than 5×10⁹/L clonal B cells without symptoms; not leukemia.
SLL
Small lymphocytic lymphoma — the same disease as CLL, mainly in the lymph nodes.
B symptoms
Fever, night sweats and unexplained weight loss.
Rai and Binet
The staging systems for CLL.
IGHV status
Whether the immunoglobulin gene is mutated or not; linked to prognosis.
del(17p) / TP53
High-risk genetic changes that affect the choice of treatment.
Coombs test
A test that detects autoantibodies against red cells.
Richter transformation
A rare change of CLL into a more aggressive lymphoma.

08Key points

  • CLL often causes no symptoms and is found on a routine blood test.
  • Possible signs: painless swollen lymph nodes, tiredness, B symptoms, infections.
  • High fever, yellow skin, sudden bleeding or fast-growing nodes need prompt attention.
  • The diagnosis is made with flow cytometry on blood; a bone marrow test is usually not needed.
  • The stage is set with the Rai or Binet system.
  • TP53/del(17p) and IGHV tests guide the choice of treatment.
  • In early disease without symptoms, watch and wait is often chosen.
  • Write down your questions and go through the results with your hematologist.

09Frequently asked questions

Isn’t waiting without treatment dangerous?

Studies have shown that in early, symptom-free CLL, immediate treatment does not help people live longer. Regular monitoring picks up when the disease becomes active, and that is when treatment brings the most benefit.

How often should I be checked?

It is individual. Monitoring is more frequent in the first period after diagnosis and, when things are stable, usually every few months. Your hematologist sets the exact plan.

Why isn’t a bone marrow test done?

CLL can be diagnosed reliably with flow cytometry on blood. A bone marrow test is usually needed only for anemia or low platelets of unclear cause, and sometimes before treatment.

Which vaccinations do I need?

The risk of infection is higher in CLL. Seasonal flu, pneumococcal and COVID-19 vaccines are usually recommended, and sometimes the recombinant shingles vaccine. Live vaccines may need to be avoided. Discuss the plan with your doctor.

Is CLL inherited?

CLL is not considered an inherited disease, but people whose close relatives have had CLL have a somewhat higher risk. Special screening of relatives is usually not recommended; if you are worried, talk to your doctor.

Why is a skin check recommended?

Some skin cancers are more common in people with CLL. Sun protection and showing your doctor any new or changing skin spots are advised.

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 is my CLL stage by Binet or Rai?

  2. How does the stage affect when treatment starts?

  3. How often will we reassess the stage?

  4. Which signs could show the stage is changing?

My questions

12Sources

  1. American Cancer Society. Signs and Symptoms of Chronic Lymphocytic Leukemia
  2. American Cancer Society. Tests for Chronic Lymphocytic Leukemia
  3. American Cancer Society. Chronic Lymphocytic Leukemia Stages
  4. National Cancer Institute (NCI). Chronic Lymphocytic Leukemia Treatment (PDQ®) — Patient Version
  5. National Cancer Institute (NCI). Chronic Lymphocytic Leukemia Treatment (PDQ®) — Health Professional Version
  6. Blood Cancer United (formerly The Leukemia & Lymphoma Society). Chronic lymphocytic leukemia (CLL) signs and symptoms
  7. Blood Cancer United (formerly The Leukemia & Lymphoma Society). Chronic lymphocytic leukemia (CLL) diagnosis
  8. National Comprehensive Cancer Network (NCCN). NCCN Guidelines for Patients: Chronic Lymphocytic Leukemia
  9. NHS. Chronic lymphocytic leukaemia — Symptoms
  10. Cancer Research UK. Tests for chronic lymphocytic leukaemia (CLL)
  11. Blood (American Society of Hematology), 2018. iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL
  12. Annals of Oncology (ESMO), 2021. Chronic lymphocytic leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
  13. The Lancet Oncology, 2016. An international prognostic index for patients with chronic lymphocytic leukaemia (CLL-IPI): a meta-analysis of individual patient data
  14. American Journal of Hematology, 2025. Chronic Lymphocytic Leukemia: 2025 Update on the Epidemiology, Pathogenesis, Diagnosis, and Therapy
  15. Leukemia (Nature) — WHO 5th edition. WHO Classification of Haematolymphoid Tumours: Lymphoid Neoplasms
Medical disclaimerThis information is for educational purposes only and does not replace medical advice.
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