Stages of Chronic Lymphocytic Leukemia (CLL)
Medically reviewed by Steffini Stalos, DOMedically reviewed by Steffini Stalos, DO
Chronic lymphocytic leukemia (CLL) is a type of cancer affecting a type of white blood cell in the blood and bone marrow. It often progresses slowly and is diagnosed most often during routine blood testing.
Understanding the stages of CLL—from stage 0 to 4—can help you navigate a CLL diagnosis. Although each increase in stage represents disease progression, you have treatment options and ways to manage symptoms to help provide a good quality of life.
This article will describe each stage’s prognosis, symptoms, and treatment options.
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Beginning to End Stages of CLL
Once diagnosed, chronic lymphocytic leukemia is staged to determine how advanced the disease is and to help determine the best treatment. The most common staging system in the United States is the Rai system.
The Rai staging system defines stages from stage 0 to stage 4 based on factors including:
Lymphocyte count (the type of white blood cell involved in CLL)
Lymph node enlargement
Spleen or liver enlargement
Low red blood cell count (anemia) or low platelet count (thrombocytopenia)
The stages of the Rai system are also described in three groups to classify risk. Stage 0 is considered low risk, stages 1 and 2 are intermediate risk, and stages 3 and 4 are regarded as high risk.
The Binet system is used more frequently in Europe. It categorizes CLL into three stages (A, B, and C) depending on the number of affected lymph tissue groups and the presence of anemia or low platelets.
In addition to the staging systems mentioned here, there is also the CLL International Prognostic Index (CLL-IPI), which considers genetic factors of an individual’s CLL in addition to blood and imaging tests.
Stage 0
Stage 0 is the earliest and most low-risk CLL stage. It is identified by an increased number of lymphocytes in the blood, but there are no other symptoms or signs of disease. Most people diagnosed with CLL will be diagnosed at stage 0. It is often found incidentally during routine blood tests.
Stage 1
In stage 1 CLL, in addition to the increased lymphocytes in the blood, there are also enlarged lymph nodes present. Red blood cells and platelets are at normal or near normal levels.
Stage 2
For stage 2 CLL, in addition to high lymphocyte levels in the blood, the liver or spleen is enlarged. Lymph nodes may or may not be enlarged as well. Red blood cell and platelet levels are at normal or near normal levels.
Stage 3
In stage 3 CLL, progression of the disease is noted with a high level of lymphocytes and anemia (a low number of healthy red blood cells). In addition to the changes in the blood levels, the lymph nodes, the spleen, or the liver may become enlarged.
Stage 4
Stage 4 CLL is the most advanced stage of the disease. It is indicated by a high lymphocyte count, anemia, and a low platelet count. There may or may not be enlargement of the lymph nodes, spleen, or liver.
How CLL Staging Affects Prognosis
The staging of CLL is an important factor in determining the prognosis and treatment strategies. Early stages, such as stage 0 and stage 1, often have a good prognosis, with many living for years without needing treatment, as the disease typically follows a slow growth pattern.
As CLL advances into further stages, it becomes more aggressive and may have a poorer prognosis. However, advancements in research and treatments have improved the outlook for CLL. The five-year relative survival for CLL in 1975 was 65.1%, but increased to 87.2% by 2021.
Progressive CLL Symptoms From Stage to Stage
Each individual living with CLL may have various symptoms associated with their disease. At an early stage, there may be no disease symptoms at all.
As CLL progresses, more symptoms may appear as the change in blood cell levels and organ and lymph node enlargement develop. The development of these symptoms can indicate active disease and may mean that treatment is necessary.
Symptoms from CLL can include:
Abdominal pain or swelling
Bleeding or bruising
Chills
Fevers
Significant fatigue
Unintentional weight loss
Treatment Options in Each CLL Stage
Treatment for CLL depends on the stage and other prognostic factors. Different treatment options are available for each stage. The exact treatment will be decided upon in consultation with an oncologist (cancer specialist).
Stage 0
In stage 0 CLL, treatment isn’t usually required. The primary medical approach is watchful waiting. During the watchful waiting period, blood work and physical exams are done routinely, often every three months, to evaluate blood levels and assess for the development of any symptoms.
Stage 1
Stage 1 CLL is still an early stage. If you are not experiencing any symptoms, no treatment is required. Watchful waiting may still be all that is needed. If there are symptoms present, treatment may be started. Treatment options are listed in the section below.
Stages 2 to 4
As CLL progresses and treatment is required, many treatment options are available. Treatments may be individualized and based on the presence or absence of genetic mutations in the CLL. Treatments may be used alone or in various combinations.
Treatment options include:
Targeted therapy
Immunotherapy
Chemotherapy
Radiation therapy
Stem cell transplant
Clinical trial
Targeted Therapy
Medications that target specific chemical pathways that impact CLL growth can be used to provide more precise treatment. These medications tend to have fewer side effects than chemotherapy (which affects all actively dividing cells).
Examples of these medications are Bruton tyrosine kinase (BTK) inhibitors like Calquence (acalabrutinib) and Imbruvica (ibrutinib), and antiapoptotic protein B cell lymphoma 2 (BCL2) inhibitors like Venclexta (venetoclax).
Immunotherapy
Immunotherapy uses the body’s immune system to help fight CLL. Some types of immunotherapy are monoclonal antibodies, manufactured immune proteins that bind to certain proteins on the outside of the cancer cells, marking them for destruction by the immune system.
Examples of immunotherapy are Rituxan (rituximab), Gazyva (obinutuzumab), and Arzerra (ofatumumab).
Chemotherapy
Chemotherapy medications kill rapidly dividing cells. Unfortunately, chemotherapy can’t tell the difference between a healthy cell and a cancer cell, so healthy cells are affected as well as unhealthy ones.
Common chemotherapy medications for CLL are Fludara (fludarabine), Cytoxan (cyclophosphamide), and Treanda (bendamustine). These may be given in combination with other treatments.
Radiation Therapy
Radiation therapy uses high-energy beams to kill cancer cells. Radiation is most often used when a small group of lymph nodes are enlarged and causing symptoms, such as pain.
Stem Cell Transplant
During a stem cell transplant, large doses of chemotherapy and possibly radiation are given to wipe out the bone marrow and cancer cells. Healthy stem cells harvested from the person (before chemo or radiation) or a donor are then infused to reestablish blood cell production.
Clinical Trial
Clinical trials may be an option for treatment. These are studies to evaluate new treatments and combinations of therapies.
CLL Testing and Follow-Up Appointments
Routine testing and follow-up appointments are needed to check for disease progression and evaluate how well treatment is working.
Initially, testing to determine the diagnosis and disease stage include:
Complete blood count (CBC) and differential: A blood test that measures and assesses blood cells
Flow cytometry: A lab technique performed on blood and other tissues to differentiate cells by their properties
Bone marrow biopsy: A procedure to obtain a sample of bone marrow (often from the hip) to assess in the lab
Imaging studies like computed tomography (CT) scans may be used to see if lymph nodes or organs are enlarged.
In routine follow-ups, blood tests and imaging may assess the progression of CLL. These visits also provide a place for discussing symptoms and receiving needed support. Keeping up with these appointments and maintaining regular communication with their oncology team empowers the person to manage CLL actively.
Summary
Chronic lymphocytic leukemia is a slow-growing cancer of the blood and bone marrow. Understanding the stages of CLL, from 0 to 4, helps determine the best treatment options.
The Rai staging system, commonly used in the United States, categorizes CLL into low, intermediate, and high risk based on factors like lymphocyte count and organ enlargement.
Early stages (0 and 1) typically have a good prognosis, with many people not requiring immediate treatment. Advanced stages (3 and 4) may need more active treatment.
Regular testing and follow-up appointments are important for monitoring disease progression and treatment effectiveness.
Read the original article on Verywell Health.
