Chronic Lymphocytic Leukemia (CLL) Stages

If you are diagnosed with chronic lymphocytic leukemia (CLL), doctors will try to figure out how advanced it is. This process is called staging.

The stage helps doctors describe how much cancer is in your body. Stages are often useful because they can help guide treatment and determine a person’s prognosis (outlook).

The stage (and outlook) for CLL is based largely on the results of blood tests, imaging tests, and physical exams.

Staging systems for chronic lymphocytic leukemia

A staging system is a standard way for the cancer care team to describe cancer. There are 2 different systems for staging CLL:

• Rai system: This is used more often in the United States.
• Binet system: This is used more widely in Europe.

Both of these staging systems are helpful and have been in use for many years.

Rai staging system

A key part of the Rai system is lymphocytosis (having too many lymphocytes in the blood) that isn't caused by anything else, like infection.

For a diagnosis of CLL, the overall lymphocyte count does not have to be high, but a person must have at least 5,000/mm³ monoclonal lymphocytes (monoclonal lymphocytosis). Monoclonal means that the cells all came from one original cell. This causes them to have the same chemical pattern, which can be seen with special lab tests.

The Rai system divides CLL into 5 stages based on the results of blood tests and a physical exam:

• Rai stage 0: Lymphocytosis; no enlargement of the lymph nodes, spleen, or liver; red blood cell and platelet counts are near normal.
• Rai stage I: Lymphocytosis with enlarged lymph nodes; spleen and liver are not enlarged; red blood cell and platelet counts are near normal.
• Rai stage II: Lymphocytosis with enlarged spleen and/or liver; lymph nodes may or may not be enlarged; red blood cell and platelet counts are near normal.
• Rai stage III: Lymphocytosis; lymph nodes, spleen, or liver may or may not be enlarged; red blood cell counts are low (anemia); platelet counts are near normal.
• Rai stage IV: Lymphocytosis; enlarged lymph nodes, spleen, or liver; red blood cell counts may be low or near normal; platelet counts are low (thrombocytopenia).

Doctors generally separate the Rai stages into low-, intermediate-, and high-risk groups when determining a person’s treatment options.

• Stage 0 is low risk.
• Stages I and II are intermediate risk.
• Stages III and IV are high risk.

Binet staging system

In the Binet staging system, CLL is classified by the number of affected lymphoid tissue groups (neck lymph nodes, groin lymph nodes, underarm lymph nodes, spleen, and liver) and by whether or not a person has anemia (too few red blood cells) or thrombocytopenia (too few blood platelets).

• Binet stage A (low risk): Fewer than 3 areas of lymphoid tissue are enlarged, with no anemia or thrombocytopenia.
• Binet stage B (intermediate risk): At least 3 areas of lymphoid tissue are enlarged, with no anemia or thrombocytopenia.
• Binet stage C (high risk): Anemia and/or thrombocytopenia is present. Any number of lymphoid tissue areas may be enlarged.

Factors that affect outlook (prognosis) for CLL

Along with the stage, there are other factors that help predict a person's prognosis (outlook). These factors are not currently part of formal staging systems, but they’re often taken into account when looking at possible treatment options.

• Factors that tend to be linked with shorter survival time are called adverse prognostic factors.
• Those linked with longer survival are favorable prognostic factors.

Adverse prognostic factors

• A deletion (loss) of part of chromosome 17 (del(17p)) in the CLL cells, and/or a mutation in the TP53 gene (which is on chromosome 17)**
•  A deletion of part of chromosome 11 (del(11q)) in the CLL cells
• Trisomy 12 (an extra chromosome 12) in the CLL cells
• Having many chromosome changes in the CLL cells (known as a complex karyotype)
• An unmutated IGHV gene in the CLL cells
• A diffuse pattern of bone marrow involvement (more widespread replacement of normal marrow by leukemia cells)
• Older age
• High blood levels of certain substances, such as beta-2-microglobulin (B2M)
• Lymphocyte doubling time (the time it takes for the lymphocyte count to double) of less than 1 year

**This is the factor most likely to affect a person’s treatment options.

Favorable prognostic factors

• Non-diffuse (nodular or interstitial) pattern of bone marrow involvement
• Deletion of part of chromosome 13 (del(13q14)) in the CLL cells, with no other chromosome abnormalities
• A mutated IGHV gene in the CLL cells

As treatment for CLL has improved over time, some of these prognostic factors have become less important.

Staging for hairy cell leukemia

There is no standard staging system for hairy cell leukemia.

Staging for small lymphocytic lymphoma (SLL)

CLL and SLL are different versions of the same disease. The cancer cells are the same, but in CLL they are mainly in the blood and bone marrow, while in SLL they’re mainly in the lymph nodes and spleen (and sometimes other organs).

However, CLL and SLL are staged differently.

CLL is staged using the Rai and Binet systems above. SLL is staged like most other types of non-Hodgkin lymphoma, using the Lugano classification, which is a modified version of the older Ann Arbor system.

For more on how SLL is staged, see Non-Hodgkin Lymphoma Stages.