Chronic Lymphocytic Leukemia
Introduction & Staging
Receiving a chronic lymphocytic leukemia (CLL) diagnosis is life-changing. Although it is a condition that is managed, not cured, it may ease your mind to know that advances in CLL treatment are being made at a rapid pace. This progress is life-changing, too, but in a much more encouraging way. More personalized treatment options are allowing many people to manage this type of blood cancer while still living life on their terms.
CLL is a type of leukemia that begins in the blood and bone marrow (the soft, spongy center of some bones). It develops from a type of white blood cell known as a lymphocyte. Lymphocytes make up lymphoid tissue, which is found in the lymph nodes, thymus, spleen, tonsils and other parts of the body. They are a part of the immune system.
When mature lymphocytes change and multiply uncontrollably, growing at a faster rate than usual and not dying when they should, they build up and circulate in the bloodstream and can spread to other parts of the body. These abnormal lymphocytes accumulate in the blood, bone marrow, lymph nodes and spleen. They interfere with the normal production of healthy cells, including red blood cells that carry oxygen, white blood cells that fight infection and platelets that help blood to clot. Patients with CLL often have larger-than-normal lymph nodes that can appear as lumps in the neck, armpits or groin regions.
Get Your Facts
Understanding the details of your diagnosis enables you to take an active role in your care. Because of the fast pace at which CLL research and advances are happening, consider choosing a hematologist with expertise in treating CLL.
Your diagnosing physician should be able to give you a referral. If a CLL specialist is not nearby and traveling is not an option, look for a CLL specialist to consult with your doctor and offer a second opinion to confirm the suggested treatment plan or add other options to consider. Connect with CLL support groups and learn how other people with CLL found their physicians. Advocacy groups, such as the CLL Society, are another resource. CLL Society’s program, Expert AccessTM, offers a free consultation to patients seeking a second opinion (cllsociety.org/programs-and-support/expert-access).
Test Results Guide Your Treatment
Your doctor will perform a physical examination to check for pain, enlarged lymph nodes and size irregularities in your spleen and other organs, as well as blood tests and genomic testing.
Blood tests are used to measure blood cell counts so your doctor can assess your risk for infections and to check that your liver and kidneys are working properly before starting treatment. Genomic testing, also called molecular profiling, tests a small sample of tissue, blood or other fluid to identify specific gene abnormalities or mutations, proteins and changes in chromosomes. These tests help distinguish CLL from other forms of leukemia, determine the subtype (B-cell CLL or T-cell prolymphocytic leukemia), check for specific markers that may help predict whether the disease will progress, and select treatment.
Genomic testing may also be used to find the following:
- TP53 gene mutation status
- Immunoglobulin heavy chain variable (IGHV) status
- Serum B2-microglobulin concentration
- Deletion of chromosomes 11q, 13q or 17p
- An extra copy of chromosome 12 (trisomy)
- NOTCH1, SF3B1 or MYD88 mutations
The tests may include the following:
- Fluorescence in situ hybridization (FISH) to examine genes or chromosomes
- Flow cytometry to look for markers
- Immunohistochemistry to verify a CLL diagnosis
- Next-generation sequencing to test multiple genes
- Karyotyping to look for abnormal chromosomes or structures
As the disease progresses, the status of your molecular test results may change. Tests will be re-run before changing the treatment strategy.
The Modified Rai Staging System and the Chronic Lymphocytic Leukemia International Prognostic Index (CLL-IPI) further assist your doctor (see Tables 1 and 2). Modified Rai offers information about how CLL may progress. CLL-IPI incorporates the Rai stage and predicts the risk of disease recurrence and overall survival.
Your doctor will also consider the clinical stage, your age and other criteria to help determine the most effective treatment.
Table 1. Modified Rai Staging System
| Stage | Risk | Description |
| Stage 0 | Low | Lymphocytosis only (the blood contains a significant number of lymphocytes). |
| Stage I | Intermediate | + Adenopathy (the blood contains a significant number of lymphocytes, and lymph nodes are enlarged). |
| Stage II | Intermediate | + Enlarged spleen and/or liver (the blood contains a significant number of lymphocytes, the spleen and/or liver is enlarged, and the lymph nodes may or may not be enlarged). |
| Stage III | High | Lymphocytosis + Hgb < 11g/dL (the blood contains a significant number of lymphocytes, and the hemoglobin is less than 11 grams per deciliter). |
| Stage IV | High | Lymphocytosis + Plt < 100,000/?L (the blood contains a significant number of lymphocytes, and the platelet count is less than 100,000 microliters). |
Table 2. Chronic Lymphocytic Leukemia International Prognostic Index (CLL-IPI)
The CLL-IPI assigns weighted values for each of the following risk factors.
| Risk factors | Points |
| TP53 mutation | 4 |
| IGHV unmutated | 2 |
| Serum B2-microglobulin more than 3.5 mg/L | 2 |
| Rai Stages I-IV | -- |
| Age older than 65 years | 1 |
