Chronic Lymphocytic Leukemia

Table of Contents

Chronic lymphocytic leukemia is a type of cancer that starts in white blood cells. White blood cells serve to help your body fight infection. Your blood cells are formed in the bone marrow. In leukemia, the bone marrow produces abnormal white blood cells. These cells expel healthy blood cells, making it difficult for the blood to do its job. In chronic lymphocytic leukemia (CLL), there are too many lymphocytes – which is a type of white blood cell.

CLL is the second most common type of leukemia occurring in middle-age people. CLL rarely affects children.

CLL doesn’t usually cause any symptoms. If you have symptoms, they may include: 

  • Painless swollen lymph nodes in the neck, armpits, stomach, or groin
  • Fatigue
  • Pain or a feeling of fullness under the ribs
  • Fever and infection
  • Weight loss

To diagnose CLL, the doctor will examine your blood, bone marrow, and lymph nodes. Your doctor may choose to monitor you until symptoms appear or change. Treatments include radiation therapy, chemotherapy, surgical removal of the spleen, and targeted therapy. Targeted therapy uses substances that attack cancer cells or block the growth and spread of cancer cells.

Overview of Chronic Lymphocytic Leukemia

Chronic lymphocytic leukemia is a type of cancer in which the bone marrow produces too many lymphocytes (a type of white blood cell).

Chronic lymphocytic leukemia (also called CLL) is a blood and bone marrow disease that can gradually worsen over time. CLL is one of the most common types of leukemia that affects middle-age adults.

Bone consists of compact bone, spongy bone, and bone marrow. Compact bone forms the outer layer of bone. Spongy bones are located at the ends of the bones and contain red bone marrow. Bone marrow is usually found in the centre of most bones and has many blood vessels. There are two types of bone marrow: red and yellow. Red bone marrow contains blood stem cells that can become red blood cells, white blood cells, or platelets, while yellow bone marrow is mostly made of fat.

Leukemia can affect red blood cells, white blood cells, and platelets.

Normally, your body produces blood stem cells (immature cells) which become mature blood cells over time. Blood stem cells can become myeloid stem cells or lymphoid stem cells.

Myeloid stem cells form one of three types of mature blood cells:

  • Red blood cells carry oxygen and other substances to the body tissues.
  • White blood cells fight infection and disease.
  • Platelets form blood clots to stop bleeding.

Lymphoid stem cells become lymphoblast cells and a type of lymphocytes (white blood cells):

  • B lymphocytes make antibodies to help fight infection.
  • T lymphocytes stimulate B lymphocytes to make antibodies to fight infection.
  • Natural killer cells attack cancer cells and viruses.

In CLL, too many blood stem cells become abnormal lymphocytes instead of healthy white blood cells. Abnormal lymphocytes are also known as leukemia cells. Lymphocytes are not able to fight infection very well. Moreover, due to the increased number of lymphocytes in the blood and bone marrow, there is less room for healthy white blood cells, red blood cells, and platelets. This can lead to infection, anemia, and easy bleeding.

Risk Factors and Symptoms of Chronic Lymphocytic Leukemia

Risk factor refers to the increased risk of getting a disease. Having risk factors does not mean you will get cancer; not having risk factors does not mean you will not get cancer either. Talk to your doctor if you think you might be at risk. Risk factors of CLL include the following:

  • Middle-aged or older males or white people.
  • Family history of CLL or lymphoma 
  • Has relatives who are of Russian Jew or Eastern European Jew descent.

In general, CLL does not cause any signs or symptoms and can be detected during routine blood tests. Signs and symptoms may be caused by CLL or other medical conditions. Check with your doctor if you have any of the following symptoms:

  • Painless swollen lymph nodes in the neck, armpits, stomach, or groin.
  • Fatigue
  • Pain or feeling full below the ribs.
  • Fever and infections
  • Weight loss for no apparent reasons

Diagnosis of Chronic Lymphocytic Leukemia

The following tests and procedures can be used to diagnose CLL:

  • Physical test and medical history: A physical test is done to check for general signs of health, including signs of disease, such as lumps or anything that seems unusual. A medical history reviews the patient’s health habits and previous illnesses and medical treatments
  • Complete blood count (CBC) with differential test: A procedure that takes blood samples which are then tested for for the following purposes:
    • The red blood cells and platelets count
    • The type of white blood cells count
    • The amount of hemoglobin (a protein that carries oxygen) in red blood cells.
    • The portion of the blood sample made up of red blood cells.

The blood sample is taken by inserting a needle into the vein – allowing blood to flow into the tube. The blood sample is sent to the laboratory and red blood cells, white blood cells, and platelets are counted. CBC is performed to test, diagnose and monitor a variety of conditions:

  • Immunophenotyping: A laboratory test to see whether the antigens or markers on the surface of blood cells or bone marrow are lymphocytes or myeloid cells. If the cells are malignant (cancerous) lymphocytes, they will be examined to see if they are B lymphocytes or T lymphocytes.
  • FISH (fluorescence in situ hybridization): A laboratory test to look at genes or chromosomes in cells and tissues. DNA fragments containing fluorescent dye are made in the laboratory and added to the cells or tissues on glass slides. When these DNA pieces bind to specific genes or chromosome areas on the slide, they light up under a microscope using a special light.
  • Flow cytometry: A laboratory test that measures the number of cells in a sample, the percentage of living cells in the sample, and certain cell characteristics – such as size, shape, and presence of the cell-surface tumor markers. The cells are stained with a light-sensitive dye, placed in a fluid, and passed through a laser or other type of light. The measurements are based on how the stained cells react to the light. 
  • IgVH gene mutation test: A laboratory test done on a bone marrow or a blood sample to check for the IgVH gene mutation. Patients with the IgVH gene mutation have a better prognosis.
  • Bone marrow aspiration and biopsy: The removal of bone marrow, blood, and a small piece of bone by inserting a hollow needle into the hip or sternum. The bone marrow, blood, and bone are viewed under a microscope to look for abnormal cells.

After a small area of ​​skin is numbed, a bone marrow needle is inserted into the patient’s hip bone. The blood, bone, and bone marrow samples are removed to be viewed under a microscope.

Prognosis of Chronic Lymphocytic Leukemia

Treatment options for CLL depend on:

  • Stages of disease.
  • Red blood cells, white blood cells, and platelets count
  • Any signs or symptoms – such as fever, chills, or weight loss.
  • Whether your liver, spleen, or lymph nodes are larger than usual.
  • Response to the initial treatment.
  • Whether CLL has recurred.

The prognosis (chances of recovery) depends on:

  • Any changes in DNA and the type of change, if any.
  • Ant lymphocytes that are scattered throughout the bone marrow.
  • Stages of disease.
  • Whether CLL improves with treatment or has recurred.
  • Whether CLL progresses to lymphoma or pro-lymphocytic leukemia.
  • The patient’s general health.

Stages of Chronic Lymphocytic Leukemia

Staging is a process used to determine how far the cancer has spread.To determine the right treatment, it is important to know the stage of the disease. The following tests can be used to determine the staging: 

  • Chest x-ray: X-ray scan to see the inside of your chest. An x-ray is a type of energy beam that can penetrate your body and onto film – creating images of areas inside the body, such as the lymph nodes.
  • MRI (magnetic resonance imaging): A procedure that uses magnets, radio waves, and a computer to create a series of detailed images of internal organs, such as the brain and spinal cord. This procedure is also called nuclear magnetic resonance imaging (NMRI).
  • CT scan (CAT scan): A procedure that produces a series of detailed images of areas inside the body taken from multiple angles. The images are created by a computer connected to an x-ray machine. The dye can be injected into a vein or swallowed to help an organ or tissue appear more clearly. This procedure is also called computed tomography, computerized tomography, or computerised axial tomography.
  • PET-CT scan: A procedure that combines images from a positron emission tomography (PET) scan and a computed tomography (CT) scan. PET and CT scans are performed at the same time with the same machine. This combined scan provides a more detailed picture of areas in the body compared. A PET scan is a procedure to find malignant tumor cells in the body. A small amount of radioactive glucose (sugar) is injected into a vein. The PET scanner rotates around the body and creates images of where glucose is being used in the brain. Malignant tumor cells appear brighter in the image because they are more active and take up more glucose than normal cells.
  • Blood chemistry study: A procedure in which a blood sample is examined to measure the amount of certain substances released into the blood by organs and tissues. Unusual amounts of substance (higher or lower than normal) can be a sign of disease.  
  • Antiglobulin test: A test to view a blood sample under a microscope. This is done to see if there are antibodies on the surface of red blood cells or platelets. These antibodies can react with and/or destroy red blood cells and platelets. This test is also known as the Coombs test.

The following are stages of chronic lymphocytic leukemia:

Stage 0

In stage 0 of chronic lymphocytic leukemia, there are too many lymphocytes, but no other signs or symptoms of leukemia. Stage 0 chronic lymphocytic leukemia is indolent (slow growth).

Stage I

In stage I of chronic lymphocytic leukemia, there are too many lymphocytes and the lymph nodes are larger than usual.

Stage II

In stage II of chronic lymphocytic leukemia, there are too many lymphocytes in the blood, larger liver or spleen. The lymph nodes may also be larger than usual.

Stage III

In stage III of chronic lymphocytic leukemia, there are too many lymphocytes and too few red blood cells. Lymph nodes, liver, or spleen may be larger than usual.

Stage IV

In stage IV of chronic lymphocytic leukemia, there are too many lymphocytes and too few platelets in your blood. The lymph nodes, liver, or spleen may be larger. Additionally, there may be too few red blood cells.

Refractory Chronic Lymphocytic Leukemia

Refractory chronic lymphocytic leukemia is a cancer that does not improve with treatment.

Treatment for Chronic Lymphocytic Leukemia

Various types of treatment are available to treat chronic lymphocytic leukemia. Some are standard treatments, and some are still in clinical trials. A clinical trial is research intended to help improve current treatments or gather information about new treatments for cancer patients. When clinical trials show that the new treatment is better than standard treatment, the new treatment can become the standard treatment. Certain clinical trials are only open to patients who have not undergone any treatment. 

Five types of standard treatment for CLL:

Observation

Observing the patient’s condition without providing any treatment until signs or symptoms appear or change. During this period, problems caused by illness, such as infections, are treated.

Radiation therapy

Radiation therapy is a cancer treatment that uses high-energy X-rays or other types of radiation to kill cancer cells or prevent them from growing. There are two types of radiation therapy:

  • External radiation therapy uses a machine outside the body to deliver radiation towards the cancer.
  • Internal radiation therapy uses a radioactive substance sealed in a needle, granule, cable, or catheter that is placed directly into or near the cancer.

Chemotherapy

Chemotherapy uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Either by oral or injection chemotherapy, the drugs enter the bloodstream and reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the cerebrospinal fluid, organs, or body cavities (e.g. the stomach), or if the drugs mainly affect cancer cells in the areas concerned, this is referred to as regional chemotherapy. Chemotherapy will depend on the type and stage of cancer. 

Surgery

Splenectomy is a surgical procedure to remove the spleen.

Targeted Therapy

Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells without damaging normal cells. Monoclonal antibody, tyrosine kinase inhibitor, and BCL2 inhibitor are types of targeted therapy used for the treatment of chronic lymphocytic leukemia.

Monoclonal antibody therapy uses antibodies made in the laboratory from a single type of immune system cell. These antibodies can identify substances on cancer cells or normal substances that can stimulate the growth of cancer cells. Antibodies attach to the substance and kill cancer cells, block their growth, or prevent them from spreading. Monoclonal antibodies are given through intravenous infusion. Antibodies can be used independently or are delivered directly to the cancer cells through medications, toxins, or radioactive materials. 

Tyrosine kinase inhibitor is a type of targeted therapy that blocks the signals required for tumors to grow.

BCL2 inhibitor therapy is a cancer treatment that blocks a protein called BCL2. BCL2 inhibitor therapy can kill cancer cells and may increase the sensitivity towards other anticancer drugs.

Stage-Based Treatment for Chronic Lymphocytic Leukemia

Stage 0 of Chronic Lymphocytic Leukemia

Treatment for stage 0 of chronic lymphocytic leukemia is usually through observation.

Stage I, Stage II, Stage III, and Stage IV of Chronic Lymphocytic Leukemia

Treatment for stage I, stage II, stage III, and stage IV of chronic lymphocytic leukemia can include the following:

  • Observation to see whether there are few or no signs or symptoms.
  • Targeted therapy with monoclonal antibodies, tyrosine kinase inhibitors, or BCL2 inhibitors.
  • Chemotherapy with one or multiple medications, with or without steroids or monoclonal antibody therapy.
  • Low-dose external radiation therapy to areas affected by cancer – such as the spleen or lymph nodes.
  • Clinical trials of chemotherapy and biological therapy with stem cell transplant.
  • Clinical trials of new treatments.

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