How Chronic Lymphocytic Leukemia (CLL) Is Staged

In This Article

Being diagnosed with chronic lymphocytic leukemia (CLL) is likely to leave you with more questions than answers. After being diagnosed, what happens next? Much of what happens is dependent upon the stage of your CLL. Staging is important as the natural progression of CLL is highly variable with survival ranging from a couple of years to more than 20 years. The staging is typically identified through physical examination and lab work.

Two systems are commonly used to help determine the stage of your CLL. The Rai system, which is commonly used in the United States, has been around since 1975 and then later modified in 1987. The Binet system, which is commonly used in Europe, was developed in 1977 and is similar to the Rai staging system. Both of these systems rely on both physical examination and laboratory data to stage CLL.

These two staging systems alone are often not enough to provide a prognosis, as some people with early-stage CLL progress faster than others. For this reason, your doctor may choose to perform other tests to further identify your prognosis.

Staging & Prognostic Methods

The Rai Staging System

The Rai staging system created by Dr. Kanti Rai in 1975 is a five-stage classification system that is also connected to a three-tiered risk stratification. Due to the five stages linking to only three survival risk categories, you may hear it described as risk categories rather than stages.

Low Risk:

  • Stage 0—Lymphocytosis (elevated lymphocytes in your blood) without enlargement of organs.

Intermediate Risk:

  • Stage 1—Lymphocytosis with enlarged lymph nodes. Normal to slightly-low red blood cell (RBC) and platelet counts.
  • Stage 2—Lymphocytosis with an enlarged spleen. Lymph nodes and the liver may also be enlarged. Normal to slightly-low red blood cell (RBC) and platelet counts.

High Risk:

  • Stage 3—Lymphocytosis in the presence of anemia (low RBC count). May or may not have enlargement of the spleen, liver, or lymph nodes. The platelet count will remain close to normal.
  • Stage 4—Lymphocytosis in the presence of thrombocytopenia (low platelet count). May or may not have anemia or enlargement of the spleen, liver, or lymph nodes.

Typically you would progress from one stage to the next with prognosis becoming worse with each advancement. With treatment, you can regress to lower risk stages with your prognosis likewise improving.

The Binet Staging System

Dr. J.L. Binet founded the Binet staging system in 1977, two years after the Rai staging system had been created. This system focuses primarily on the number of lymphoid structures that are enlarged. The sites can be either on only one side of the body or both sides of the body and still count as one area if it is the same structure. While there are many lymphoid sites in the body, the following five are assessed in the Binet staging system:

  • Cervical lymph node
  • Axillary lymph node
  • Inguinal lymph node
  • Spleen
  • Liver

The Binet staging system consists of the following 3 categories:

  • Stage A—Less than three enlarged lymphoid sites without anemia (low RBC count) or thrombocytopenia (low platelet count).
  • Stage B—Three or more enlarged lymphoid sites without anemia or thrombocytopenia.
  • Stage C—Anemia and thrombocytopenia with or without enlarge lymphoid sites

Combining either the Rai or Binet staging system with other prognostic tests can help you better understand the severity of your CLL and your overall prognosis.

CLL-International Prognostic Index

The CLL-International Prognostic Index (CLL-IPI) may be used in addition to the Rai or Binet staging systems. The CLL-IPI incorporates additional information that is available through lab testing by looking at age, genetic, biochemical and physical findings. The overall index score is the combination of points from the following factors:

  • TP53 deleted or mutated—4 points
  • Unmutated IGHV—2 points
  • Rai stage (1-4) or Binet stage (B-C)—1 point
  • Age greater than 65 years—1 point

Treatment recommendation can then be determined by the following point-driven categories:

  • Low Risk (0-1 points)—No treatment
  • Intermediate Risk (2-3 points)—No treatment unless highly symptomatic
  • High Risk (4-6 points)—Treat unless asymptomatic (experiencing no symptoms of disease)
  • Very High Risk (7-10 points)—If treating use novel or medications undergoing trials before chemotherapy

Physical Examination

Lymph Node Exam

The physical examination is important in staging chronic lymphocytic anemia as it is one of the two aspects required to accurately stage this disease. The exam is relatively simple in that your physician will be looking for enlarged lymphoid organs. Lymphoid tissue contains lymphocytes and macrophages which make up our white blood cells which play an important role in our immune system.

Your doctor will systematically move through several lymph nodes to identify if there is any enlargement. A thorough physical exam to identify lymph node involvement will include palpating (examination by touch) your neck (cervical lymph nodes), armpits (axillary lymph nodes), and the groin (inguinal lymph nodes). They will also want to palpate your spleen and liver.

Spleen Exam

Your spleen is located in the upper left part (quadrant) of your abdomen. To evaluate for an enlarged spleen, which is referred to as splenomegaly, your doctor may perform one to four different exams. In order to perform this, you will be asked to lie down on your back and will be asked to bend your knees. Not all steps are required to determine if you have an enlarged spleen.

  1. Inspection—You should typically not be able to see the spleen, however, an enlarged spleen may be visible during inspiration.
  2. Auscultation—If your spleen cannot be seen during inspiration, your doctor will listen with a stethoscope for a splenic rub. A rub is a frictional noise that occurs when the spleen is enlarged. If you are suffering from pain in your left upper abdomen or the top of your left should when you breathe in, a splenic rub should definitely be auscultated for.
  3. Palpation—With knees bent, your doctor will systematically feel around your left upper abdomen. They will press deeply and release several times and will instruct you when to breathe in. If your doctor is unsuccessful in finding your spleen, they may ask you to turn onto your right side to continue palpating for your spleen. Unless you are a young and thin adult, your spleen will not be able to be palpated unless it is enlarged.
  4. Percussion—If your doctor is still uncertain if you have an enlarged spleen, they may decide to percuss (gently tap) your abdomen. In the same positions as with palpation, your doctor will percuss your upper left abdomen during both inspiration and expiration. If there is a dull sound during inspiration, but not during expiration, an enlarged spleen may be the cause.

Liver Exam

The liver is the largest organ in the body, but even with as large as it is, you should not typically be able to see it, as most, if not all, of your liver should reside behind your right rib cage. As your liver is a lymphoid organ, it can become enlarged due to chronic lymphocytic leukemia. For this physical exam, you will be asked to lie on your left side, exposing your right side for your doctor to assess. You should try to relax and avoid flexing your abdomen, as it will make the examination more difficult. It may help to bend your knees and/or place a pillow between your legs to become more comfortable. You can expect these possible steps in a liver exam to determine if you have an enlarged liver (hepatomegaly); you will notice that the order is different than a spleen exam:

  1. Inspection—When the liver is enlarged, your doctor may be able to see the edges of the liver below the rib cage without further inspection.
  2. Percussion—Your doctor may percuss (tap) your chest to determine the borders of your liver where a dull sound will be noted. Typically the top of the liver can be identified close to your right nipple and can be identified by heavy percussion. The bottom of the liver is best identified with light percussion at the bottom of your right rib cage, which is also known as the right costal margin.
  3. Palpation—Your doctor will press down on your abdomen slightly below where the edge of the liver was identified during percussion. They will then lift up until they can palpate the liver.

It is important to understand that even with a normal-sized liver, you may experience mild momentary pain. If you have an enlarged and inflamed liver, you will experience moderate momentary pain. The pain will quickly subside and does not cause harm.

Labs and Tests

Complete Blood Count

A complete blood count (CBC) is one of the most common tests that will be performed during testing for CLL. An abnormal CBC may be one of the tests that lead to further testing in the diagnosis of CLL. It is also a test that is important in staging chronic lymphocytic leukemia. A CBC test contains information related to:

A standard CBC will only contain information related to the total white blood cell count. Often it will be a standard CBC that shows an elevated white blood cell count. In order to differentiate what cell type is elevating your WBC, a CBC with differential will need to be ordered. Future tests during treatment will likely also be a CBC with differential to evaluate the effectiveness of therapy or further staging.

Prognostic Tests

While staging CLL can help drive understanding of where in the course of leukemia you are in, it does not provide specifics about your prognosis or future course of disease and life expectancy. You and your doctor may want further testing to help clarify your prognosis. These tests having varying success in determining your prognosis and further research in this area is ongoing.

Genetic studies may be looked at to look for specific genes. The genes del(13q) and trisomy 12 have been associated with favorable prognosis. While on the other hand, del(17p) and del(11q) have been associated with future relapse and initially failing treatments. With genetic research improved treatment of del(11q) has specifically shown to respond better to Fludara (fludarabine), Cytoxan (cyclophosphamide), and Rituxan (rituximab). While del(17p) is also identified with other TP53 gene mutations that remain resistant to treatment. Continued genetic research is ongoing to identify better treatment combinations and understanding genetics in relation to prognosis.

Lymphocyte doubling time (LDT) is a lab test that determines how long it takes your lymphocyte count to double. Typically an LDT of less than 12 months signifies a more progressive disease, while an LDT of greater than 12 months is associated with a slower progressive state.

Immunoglobulin heavy chain variable region (IGHV) mutation status is identified as either unmutated or mutated. Unmutated IGHV is associated with an increased risk of relapse following treatment as well as an overall poorer prognosis. If you have unmutated IGHV, you may also be more susceptible to other CLL complications such as autoimmune disorders, infections, and Richter transformation. Mutated IGHV is more favorable. This test is an important aspect of the CLL-International Prognostic Index.

Other markers can be used to help clarify your prognosis:

  • Beta-2 Microglobulin—Increasing levels associated with increased tumor burden and poorer prognosis.
  • CD38—Detection associated with a poorer prognosis.
  • ZAP-70—Increased levels associated with poorer prognosis and is often found if you have unmutated IGHV.

Imaging

Imaging studies such as CT scans, MRIs, X-rays, and ultrasounds are of little to no utility in the staging or prognosis of chronic lymphocytic leukemia. Staging relies on the physical examination findings which do not require any radiological assessment. However, if there is difficulty in determining whether the liver or spleen is enlarged an ultrasound may be helpful in diagnosing splenomegaly or hepatomegaly.

Was this page helpful?
Article Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Rai KR, Stilgenbauer S. Staging and prognosis of chronic lymphocytic leukemia. UpToDate. Updated February 14, 2018.

  2. American Cancer Society. How is chronic lymphocytic leukemia staged? Updated May 10, 2018.

  3. Leukemia & Lymphoma Society. CLL staging.

  4. Hallek M. Chronic lymphocytic leukemia: 2017 update on diagnosis, risk stratification, and treatment. Am J Hematol. 2017 Sep;92(9):946-965. doi:10.1002/ajh.24826.

  5. International CLL-IPI working group. An international prognostic index for patients with chronic lymphocytic leukaemia (CLL-IPI): a meta-analysis of individual patient data. Lancet Oncol. 2016 Jun;17(6):779-790. doi: 10.1016/S1470-2045(16)30029-8

  6. Armitage JO. Spleen. In: Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition.

  7. Wolf DC. Evaluation of the size, shape, and consistency of the liver. In: Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition.

  8. American Cancer Society. Tests for chronic lymphocytic leukemia. Updated May 10, 2018.

  9. Rodrigues CA, Gonçalves MV, Ikoma MR, et al. Diagnosis and treatment of chronic lymphocytic leukemia: recommendations from the Brazilian Group of Chronic Lymphocytic LeukemiaRev Bras Hematol Hemoter. 2016;38(4):346–357. doi:10.1016/j.bjhh.2016.07.004

Additional Reading
  • Byrd JC. Chronic lymphocytic leukemia. In: Byrd JC, ed. Goldman-Cecil Medicine, 2-volume Set. Philadelphia: Elsevier. 174, 1217-1224.e2. 2015.