How Is Chronic Lymphocytic Leukemia Staged?

For most cancers, staging is the process of finding out how far the cancer has spread. Stages are often useful because they can help guide treatment and determine a person's outlook. Most types of cancer are staged based on the size of the tumor and how far the cancer has spread.

Chronic lymphocytic leukemia (CLL), on the other hand, does not usually form tumors. It's generally in the bone marrow and blood. And, in many cases, it has spread to other organs such as the spleen, liver, and lymph nodes by the time it's found. The outlook for a person with CLL depends on other information, such as the results of lab test and imaging tests.

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

The Rai system is based on lymphocytosis. The patient must have a high number of lymphocytes in their blood and bone marrow that isn't linked to any other cause (like infection).

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

This 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; enlarged lymph nodes; spleen and liver are not enlarged; red blood cell and platelet counts are near normal.
• Rai stage II: Lymphocytosis; enlarged spleen (and maybe an enlarged 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 separate the Rai stages into low-, intermediate-, and high-risk groups when determining treatment options.

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

These risk groups are used later in Treatment of Chronic Lymphocytic Leukemia.

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 the patient has anemia (too few red blood cells) or thrombocytopenia (too few blood platelets).

• Binet stage A: Fewer than 3 areas of lymphoid tissue are enlarged, with no anemia or thrombocytopenia.
• Binet stage B: 3 or more areas of lymphoid tissue are enlarged, with no anemia or thrombocytopenia.
• Binet stage C: Anemia and/or thrombocytopenia are present. Any number of lymphoid tissue areas may be enlarged.

Prognostic factors for chronic lymphocytic leukemia

Along with the stage, there are other factors that help predict a person's outlook. These factors are not part of formal staging systems (at least at this time), but are 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 that predict longer survival are favorable prognostic factors.

Adverse prognostic factors

• Diffuse pattern of bone marrow involvement (more widespread replacement of normal marrow by leukemia)
• Advanced age
• Deletions of parts of chromosomes 17 or 11
• Trisomy 12 in the CLL cells
• High blood levels of certain substances, such as beta-2-microglobulin
• Lymphocyte doubling time (the time it takes for the lymphocyte count to double) of less than 1 year
• Increased fraction of prolymphocytes (an early form of the lymphocyte) in the blood
• High proportion of CLL cells containing ZAP-70 (20% or more) or CD38 (30% or more)
• CLL cells with unchanged (not mutated) gene for the immunoglobulin heavy chain variable region (IGHV)
• CLL cells don't have the TP53 gene

Favorable prognostic factors

• Non-diffuse (nodular or interstitial) pattern of bone marrow involvement
• Deletion of part of chromosome 13 (with no other chromosome abnormalities)
• Low proportion of CLL cells containing ZAP-70 (less than 20%) or CD38 (less than 30%)
• CLL cells with a mutated gene for IGHV

Certain prognostic factors such as the presence or absence of ZAP-70, CD38, and a mutated gene for IGHV help divide cases of CLL into 2 groups, slow growing and fast growing. People with the slower growing kind of CLL tend to live longer and may be able to delay treatment longer as well.

Staging for hairy cell leukemia

There is no standard staging system for hairy cell leukemia.

Monoclonal B-lymphocytosis

Some people have monoclonal lymphocytes in their blood, but not enough to make the diagnosis of CLL. If someone has less than 5,000 monoclonal lymphocytes (per mm³), normal counts of red blood cells and platelets, and no enlarged lymph nodes (or enlarged spleen), they have a condition called monoclonal B-lymphocytosis (MBL). MBL doesn’t need to be treated, but about one patient of every 100 with this condition will go on to need treatment for CLL.

Small lymphocytic lymphoma

The cancer cells of small lymphocytic lymphoma (SLL) and CLL look the same under the microscope and have the same marker proteins on the surface of the cells. Whether someone is diagnosed with SLL or CLL depends largely on the number of lymphocytes in the blood. To be diagnosed with CLL, there must be at least 5,000 monoclonal lymphocytes (per mm³) in the blood. For it to be called SLL, the patient must have enlarged lymph nodes or an enlarged spleen with fewer than 5 ,000 lymphocytes (per mm³) in the blood. Still, since SLL and CLL can be treated the same, the difference between them isn't really important.