Chronic Lymphocytic Leukemia Diagnosis and Staging

April 19, 2024 
This page was reviewed under our medical and editorial policy by Guido Marcucci, M.D., Chair, Department of Hematologic Malignancies Translational Science, City of Hope Duarte

Chronic lymphocytic leukemia (CLL) is a type of blood cancer diagnosed with a variety of medical tests. Once a diagnosis is made, further tests help the health care team determine how much the cancer has grown and/or spread. This step is called staging, and it helps doctors to align a chronic lymphocytic leukemia treatment plan with the characteristics of the cancer.

This guide is designed to help patients and their families learn more about CLL diagnosis and staging.

How Is Chronic Lymphocytic Leukemia Diagnosed?

Diagnosis of chronic lymphocytic leukemia starts with a physical exam and blood testing.

Physical Exam

During a physical exam, a doctor reviews a patient’s medical history, looking for any personal or family risk factors and checking for any physical signs and symptoms that may indicate disease.

Blood Testing

  • A complete blood count (CBC) measures the number of different blood cells within the body. With CLL, test results show too many white blood cells, or lymphocytes.
  • A peripheral blood smear may also be performed on a blood sample, which examines blood cells under a microscope to look for abnormal cells called smudge cells (flattened lymphocytes) that may be evidence of CLL.
  • Flow cytometry is performed on blood samples and is a key diagnostic tool to confirm CLL. It uses a machine to organize and examine cells and look for CLL markers on or in blood cells.
  • Cytochemistry may also be performed on blood samples. This involves staining cells to look for chemical markers of CLL.

These blood tests often confirm a diagnosis of CLL.

Some patients may have symptoms of CLL, which leads to blood testing. For others without symptoms, CLL may be initially detected through routine blood tests performed for other reasons, which may then be followed up with more specific blood testing.

To stage the cancer, monitor how it’s responding to treatment and learn more about the characteristics of the leukemia cells, the tests listed below may also be performed.

Bone Marrow Aspiration and Biopsy

During a bone marrow aspiration, a hollow needle is used to remove a sample of liquid bone marrow. During the procedure, patients are given either local anesthesia (to numb the biopsy site) or general anesthesia (which puts them to sleep). A biopsy is often done as well to collect a small sample of bone and marrow (the spongy tissue inside bones). During this procedure, the patient is under anesthesia so as to alleviate any pain.

These samples are most often taken from the hip. After the aspiration and biopsy, the samples are examined under a microscope to look at the traits of the cells and learn more about prognosis.

Lumbar Puncture

A lumbar puncture is a procedure to remove a sample of fluid from the spine to test for cancer cells.

Also called a spinal tap, this test is generally used only when doctors want to see if CLL has moved into the brain or spinal cord.

Lymph Node Biopsy 

During a lymph node biopsy, all or part of a lymph node is surgically removed and examined under a microscope to look for cancer cells. This test is more often used for lymphoma than for leukemia.

Imaging Tests

While not generally used as initial diagnostic tools for CLL, imaging tests such as X-rays, computed tomography (CT) scans and ultrasounds are used to see if a cancer has spread or how it’s responding to treatment.

Genetic Testing

CLL affects different genes in different ways across patients. Genetic testing may be recommended to determine the specific gene mutations in the leukemia cells. Some of these changes help to inform treatment and prognosis.

Chronic Lymphocytic Leukemia Stages

Blood cancers don’t form solid tumors, which means staging of CLL is different from that of other cancers. In the United States, the Rai system is most often used; in Europe, a method called Binet classification is more common.

In the Rai system, CLL is given one of the stages listed below.

  • Stage 0: The patient has no physical CLL symptoms, but has high levels of white blood cells called lymphocytes in the blood.
  • Stage 1: The patient has high levels of lymphocytes (lymphocytosis), as well as enlarged lymph nodes.
  • Stage 2: The patient has high levels of lymphocytes and an enlarged liver and/or spleen. In Stage 2, the lymph nodes may or may not be enlarged.
  • Stage 3: The patient has lymphocytosis as well as anemia. The spleen, liver and/or lymph nodes may be enlarged.
  • Stage 4: The patient has lymphocytosis and low platelet levels, and may or may not have an enlarged spleen and/or liver, anemia and enlarged lymph nodes.

These stages are also classified into the risk groups listed below, which help doctors predict whether the disease is likely to increase in severity over time, requiring additional treatment.:

  • Stage 0: Low risk
  • Stages 1 and 2: Intermediate risk
  • Stages 3 and 4: High risk

If patients wish to learn more, their health care team may provide expert and caring advice, and is available to answer questions about how their CLL staging and risk affect their treatment plan.

  • American Cancer Society (2018, May 10). How Is Chronic Lymphocytic Leukemia Diagnosed?

  • American Society of Clinical Oncology (2017, October). Leukemia - Chronic Lymphocytic - CLL: Diagnosis.

  • American Society of Clinical Oncology (2017, October). Leukemia - Chronic Lymphocytic - CLL: Stages.