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 prognosis (outlook). Most types of cancer are staged based on the size of the tumor and how far in the body the cancer has spread.

Chronic lymphocytic leukemia (CLL), on the other hand, does not usually form tumor masses. It generally involves all of the bone marrow in the body and, in many cases, has spread to other organs such as the spleen, liver, and lymph nodes when it is found. Therefore the outlook for the patient with CLL depends on other information, such as the lab test results and the results of imaging tests.

Staging for chronic lymphocytic leukemia

A staging system is a standardized way for the cancer care team to summarize information about how far a cancer has spread. 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.

There are also other factors that have been found to affect prognosis, which are discussed below.

Rai staging system

The Rai system divides CLL into 5 stages:

• Rai stage 0: The blood lymphocyte count is too high, usually defined as over 10,000 lymphocytes/mm3 of blood (this is called lymphocytosis). Some doctors will diagnose CLL if the count is over 5,000/mm3 and the cells all have the same chemical pattern on special testing. The lymph nodes, spleen, and liver are not enlarged and the red blood cell and platelet counts are near normal.
• Rai stage I: Lymphocytosis plus enlarged lymph nodes. The spleen and liver are not enlarged and the red blood cell and platelet counts are near normal.
• Rai stage II: Lymphocytosis plus an enlarged spleen (and possibly an enlarged liver), with or without enlarged lymph nodes. The red blood cell and platelet counts are near normal.
• Rai stage III: Lymphocytosis plus anemia (too few red blood cells), with or without enlarged lymph nodes, spleen, or liver. Platelet counts are near normal.
• Rai stage IV: Lymphocytosis plus thrombocytopenia (too few blood platelets), with or without anemia, enlarged lymph nodes, spleen, or liver.

For practical purposes, doctors separate the Rai stages into low-, intermediate-, and high-risk groups when determining treatment options.

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

These risk groups are used later in this document in the section called "How is chronic lymphocytic leukemia treated?"

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.

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

In recent years, doctors have found that other factors can also help predict a person's outlook. The factors described below are not part of formal staging systems (at least at this time), but they can also provide helpful information.

Prognostic factors for chronic lymphocytic leukemia

Along with the stage, there are other factors that help predict a person's outlook. These factors are sometimes 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
• Male gender
• Deletions of parts of chromosomes 17 or 11
• 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 12 months
• Increased proportion of large or atypical lymphocytes in the blood
• High proportion of CLL cells containing ZAP-70 (more than 20%) or CD38 (more than 30%)
• CLL cells with unchanged (not mutated) gene for the immunoglobulin heavy chain variable region (IgV_H)

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 (20% or less) or CD38 (30% or less)
• CLL cells with a mutated gene for the immunoglobulin heavy chain variable region (IgV_H)

Some of these prognostic factors, such as the presence or absence of ZAP-70 and CD38, will probably become more important over time, and may eventually be found to be better predictors of outcome than the staging systems, particularly for people in the earliest stages of CLL.

Staging for hairy cell leukemia

There is no generally accepted staging system for hairy cell leukemia.