Chronic Lymphocytic Leukemia (CLL) - Staging and Treatment
What is staging for cancer?
Staging is the process of learning how much cancer is in your body and where it is. While most cancers form tumors, CLL does not. It is found in the blood and bone marrow but also can be found in organs of the body. Tests like blood counts, flow cytometry to look for markers on cancer cells, bone marrow biopsy, and blood tests to look at chromosomal changes are done to help stage your cancer. Your providers need to know about your cancer and your health so that they can plan the best treatment for you.
How is CLL staged?
There are two different staging systems for CLL:
- Rai Staging System: Based on results of blood tests (especially the number of white blood cells) and physical exam.
- Binet Staging System: Based on the number of affected lymphoid tissue groups and if you have anemia (low red blood cell count) or thrombocytopenia (low platelet count).
Rai Staging System
In each stage, there is lymphocytosis. Lymphocytosis is a higher-than-normal white blood cell (WBC) count. The extra WBCs are found in the blood and bone marrow.
- Stage 0: Lymphocytosis but no enlargement of lymph nodes, spleen, or liver, and red blood cell and platelet counts are almost normal.
- Stage I: Lymphocytosis with enlarged lymph nodes. The spleen and liver are not affected, and red blood cell and platelet counts are almost normal.
- Stage II: Lymphocytosis with an enlarged spleen and in some cases an enlarged liver. Lymph nodes may or may not be enlarged. Red blood cell and platelet counts are almost normal.
- Stage III: Lymphocytosis plus the lymph nodes, spleen or liver may or may not be enlarged. Red blood cell count is low, and platelets are near normal.
- Stage IV: Lymphocytosis plus enlarged lymph nodes, spleen, or liver. Red blood cell counts may be low or near normal and the platelet count is low.
Each stage is also put into a risk group that helps decide which treatments are best:
- Stage 0: Low risk.
- Stage I and II: Intermediate risk.
- Stage III and IV: High Risk.
Binet Staging System
The Binet system looks at lymphoid tissue, anemia, and thrombocytopenia. Lymphoid tissue groups include the neck lymph nodes, groin lymph nodes, underarm lymph nodes, spleen, and liver.
- Stage A: Fewer than 2 areas of lymphoid tissue are enlarged, no anemia, and no thrombocytopenia.
- Stage B: 3 or more areas of enlarged lymphoid tissue, no anemia, and no thrombocytopenia.
- Stage C: Any number of lymphoid areas are enlarged, and anemia and thrombocytopenia are present.
Although not part of the formal staging systems, prognostic factors can help determine treatment for CLL. There are both adverse and favorable prognostic factors. Your provider will be able to tell you if you have any prognostic factors and how they will affect your treatment.
How is CLL treated?
Treatment for CLL will depend on the stage of your disease, your current health, and your goals. You and your care team will decide what will be the best course of treatment. Treatments can include:
People with early-stage or less aggressive disease can have better outcomes if treatment is not started until disease-related symptoms start or there is a rapid doubling time. The treatment for a stage 0 CLL is often observation.
Even if CLL is not being treated, there are certain supportive care measures that should be taken. CLL affects a person's ability to fight infection. The best way to prevent infection is hand washing, by you and those you come in contact with. Avoid large crowds, like a shopping mall on the busiest shopping day of the year! The common cold, flu, or pneumonia can be life-threatening for a person with CLL. Vaccines, like the flu vaccine, are less effective in people with CLL. You should talk to your provider about if and when you should get vaccines.
People with anemia can have fatigue, shortness of breath, or look pale. Medications and blood transfusions can be used to treat anemia. Thrombocytopenia can lead to bleeding that is hard to stop. This can be as small as gums bleeding when brushing the teeth or a nosebleed to dangerous bleeding, such as a stroke. You should avoid contact sports, shaving (using an electric razor is okay), or any activities that increase the risk of bleeding or bruising. Tell your provider if you are having symptoms of thrombocytopenia. You are also at risk for tumor lysis syndrome (TLS) which is the rapid breakdown of cells that causes an imbalance of chemicals and electrolytes in the body. TLS impacts levels of uric acid, potassium, phosphate, and calcium and can cause kidney failure, seizures, and heart rhythm changes.
Radiation is the use of high-energy x-rays to kill cancer cells. It is not used to treat CLL but can be used as a supportive care measure. Radiation may be used to help shrink an organ that has become enlarged and is causing pain. It can also be used to treat bone pain. Leukemia cells grow in the bone marrow and can cause this pain.
Chemotherapy is a medication that kills cancer cells. Chemotherapy travels throughout the bloodstream to kill cancer cells. You will be prescribed a regimen that lasts from days to weeks that includes a few different kinds of chemotherapy. Examples of chemotherapy medications used to treat CLL include bendamustine, chlorambucil, pentostatin, cyclophosphamide, fludarabine, and cladribine. Steroids may be given with chemotherapy or alone to treat CLL. Examples of steroids used to treat CLL are prednisone and methylprednisolone.
Targeted therapy is a medication or drug that targets a specific pathway in the growth and development of a tumor cell. The targets themselves are often various molecules (or small particles) in the body that are known or thought to play a role in cancer formation. The two types of targeted therapy used in the treatment of CLL are monoclonal antibodies and kinase inhibitors.
Monoclonal antibodies are man-made antibodies that attach to a cancer cell. The body starts an immune response, and the cells are destroyed by your immune system. Examples of monoclonal antibodies are obinutuzumab, ofatumumab and rituximab. They are all given intravenously (IV, into a vein).
Kinase inhibitors block growth signals within cancer cells, reducing the production of new cancer cells. Examples of kinase inhibitors include acalabrutinib, ibrutinib, duvelisib, and idelalisib. Another targeted therapy that may be used in the treatment of CLL is venetoclax. Individualized immune therapy called CD19 Chimeric Antigen Therapy (CAR-T) is currently being studied in CLL patients.
If you have splenomegaly (enlarged spleen) you may have a splenectomy, or removal of the spleen. The spleen helps to filter old, unneeded cells from the blood. People without a spleen are at a higher risk of infection.
Bone Marrow Transplant
Transplants can be done using a donor's bone marrow or stem cells (allogeneic) or your own bone marrow or stem cells (autologous). Allogeneic transplants are more commonly used in patients with CLL. Giving you a donor's marrow after marrow-killing (marrow-ablating) chemotherapy serves to "rescue" you with healthy bone marrow. One effect that providers see as a very important part of all allogeneic transplants is called the "graft versus tumor effect.” This is the effect that the donor's immune system (which is part of the marrow that the donor donated) has on your cancer cells. The hope is that the healthy donor immune system can attack any stray cancer cells that survived the treatment before the transplant.
You may be offered a clinical trial as part of your treatment plan. To find out more about current clinical trials, visit the OncoLink Clinical Trials Matching Service.
Making Treatment Decisions
Your care team will make sure you are included in choosing your treatment plan. This can be overwhelming as you may be given a few options to choose from. It feels like an emergency, but you can take a few weeks to meet with different providers and think about your options and what is best for you. This is a personal decision. Friends and family can help you talk through the options and the pros and cons of each, but they cannot make the decision for you. You need to be comfortable with your decision – this will help you move on to the next steps. If you ever have any questions or concerns, be sure to call your team.
You can learn more about CLL at OncoLink.org.
American Cancer Society. Chronic Lymphocytic Leukemia. CLL.
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