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 is in all of the bone marrow 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.
Rai staging system
The Rai system was originally devised in 1968. At that time, all that was needed to diagnose CLL was lymphocytosis - a high number of lymphocytes in the blood and bone marrow that didn’t have any other cause (like infection). This was originally defined as over 15,000 lymphocytes/mm3 of blood and at least 40% of the bone marrow being made up of lymphocytes.
Now, for a diagnosis of CLL, the patient must have at least 5,000/mm3 of monoclonal lymphocytes (sometimes called a monoclonal lymphocytosis), but the overall lymphocyte count does not have to be high. Monoclonal means that the cells all came from the same cell, and so have the same chemical pattern on special testing.
For the purposes of this staging, you can substitute a diagnosis of CLL (such as with a monoclonal lymphocytosis) for lymphocytosis.
This system divides CLL into 5 stages:
- Rai stage 0: Lymphocytosis and no enlargement of the lymph nodes, spleen, or liver, and with near normal red blood cell and platelet counts.
- 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.
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.
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 6 months
- Increased fraction of prolymphocytes (an early form of the lymphocyte) 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 (IGHV)
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 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 generally accepted staging system for hairy cell leukemia.
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 markers (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 at least 5,000 monoclonal lymphocytes (per mm3) in the blood. For it to be called SLL, there needs to be less than 5,000 lymphocytes (per mm3), but (unlike MBL) the patient also needs to have enlarged lymph nodes or an enlarged spleen. Still, since SLL and CLL can be treated the same, the difference between the 2 is not really important.
Last Medical Review: 07/31/2013
Last Revised: 04/18/2014