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For most cancers, staging is the process of determining and characterizing how much a cancer has spread. Identifying the stage, or level of progress, can often be useful because it 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 the cancer has spread.
Chronic lymphocytic leukemia (CLL) does not typically form tumors, but rather it presents in the bone marrow, blood and lymph nodes. In some cases, by the time it is discovered, it has also spread to other organs such as the spleen, liver, and lymph nodes. Because of this, the outlook for a person with CLL may depend on other information, such as all the lab test results. Imaging such as CT or PET scan at the time of diagnosis is most often not necessary in CLL.
In the United States, the most commonly used clinical staging system for chronic lymphocytic leukemia (CLL) is the Rai staging system developed by Dr. Kanti Rai in 1975. Rai staging is based simply on blood tests and physical exam (no imaging tests). The Rai system divides CLL into 5 stages:
Decades later, physicians still use the Rai stages as a way of describing the level of risk from CLL for each patient. The level of risk helps to determine the best CLL management when used with other newer prognostic factors.
- Stage 0 is low-risk.
- Stages I and II are intermediate-risk.
- Stages III and IV are high-risk.
Staging in CLL/SLL should not use the Ann Arbor staging system, which would automatically classify the all CLL as stage IV, because all cases of CLL have tumor cells in the bone marrow.
Along with the staging, there are many 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.
Minimum testing should include FISH, TP53 testing and IgHV mutation. FISH and TP53 can change so they must be retested before each treatment.
Adverse prognostic factors
- Deletions of chromosomes 17p or 11q. These are found by Fluorescence In Situ Hybridization (FISH) testing that can determine the status of specific CLL chromosomes in the blood, bone marrow or lymph
- TP53 gene mutation usually found by next generation gene sequencing. TP53 is on the short arm of chromosome 17 (17p) so when it is deleted, TP53 is nonfunctional. These two, 17p deletion and TP53 are critical predictive risk factor in deciding the best treatment
- High blood levels of certain substances, such as beta-2-microglobulin (B2M)
- If the lymphocyte count doubles in less than 6 months (Lymphocyte doubling time or LDT)
- More than 20% of CLL cells containing ZAP-70 or more than 30% containing CD38
- Un-mutated gene for the immunoglobulin heavy chain variable region (IgHV)
- Complex Karyotype (multiple changes in the CLL genetic material)
- More widespread bone marrow involvement
- Advanced age and/or male gender
Favorable prognostic factors
- Non-diffuse (nodular or interstitial) pattern of bone marrow involvement
- Deletion 13q with no other chromosome abnormalities found by FISH
- CLL cells with a mutated gene for IgHV
Please note that this is a partial list of prognostic factors. Some factors become obsolete due to new therapies and diagnostic tools, and are replaced or supplemented by newer factors.
Also remember that while these factors may reliably predict for a group of patients, they do not for any one individual. Each one of us of is different.
All these factors and staging are becoming less “prognostic” in the era of new therapies as many new therapies are agnostic to what would be unfavorable factors with chemo-immunotherapy.
They might be better used be in guiding therapy choices.