Chronic Lymphocytic Leukaemia

• Chronic lymphocytic leukaemia is a type of cancer in which the bone marrow makes too many lymphocytes (a type of white blood cell).
• Older age can affect the risk of developing chronic lymphocytic leukaemia.
• Possible signs of chronic lymphocytic leukaemia include swollen lymph nodes and tiredness.
• Tests that examine the blood, bone marrow, and lymph nodes are used to detect (find) and diagnose chronic lymphocytic leukaemia.
• Certain factors affect treatment options and prognosis (chance of recovery).

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

Chronic lymphocytic leukaemia (also called CLL) is a blood and bone marrow disease that usually gets worse slowly. CLL is the second most common type of leukaemia in adults. It often occurs during or after middle age; it rarely occurs in children.

Normally, the body produces bone marrow stem cells (immature cells) that develop into mature blood cells. There are 3 types of mature blood cells:

• Red blood cells that carry oxygen and other materials to all tissues of the body.
• White blood cells that fight infection and disease.
• Platelets that help prevent bleeding by causing blood clots to form.

In CLL, too many stem cells develop into a type of white blood cell called lymphocytes. There are 3 types of lymphocytes:

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

The lymphocytes in CLL are not able to fight infection very well. Also, as the amount of lymphocytes increases in the blood and bone marrow, there is less room for healthy white blood cells, red blood cells, and platelets. This may result in infection, anemia, and easy bleeding.

This summary is about chronic lymphocytic leukaemia. Refer to the following summaries for more information about leukaemia:

• Adult Acute Lymphoblastic Leukaemia Treatment.
• Childhood Acute Lymphoblastic Leukaemia Treatment.
• Adult Acute Myeloid Leukaemia Treatment.
• Childhood Acute Myeloid Leukaemia/Other Myeloid Malignancies Treatment.
• Chronic Myelogenous Leukaemia Treatment.
• Hairy Cell Leukaemia Treatment.

Older age can affect the risk of developing chronic lymphocytic leukaemia.

Risk factors for CLL include the following:

• Being middle-aged or older, male, or white.
• A family history of CLL or cancer of the lymph system.
• Having relatives who are Russian Jews or Eastern European Jews.

Possible signs of chronic lymphocytic leukaemia include swollen lymph nodes and tiredness.

Usually CLL does not cause any symptoms and is found during a routine blood test. Sometimes symptoms occur that may be caused by CLL or by other conditions. A doctor should be consulted if any of the following problems occur:

• Painless swelling of the lymph nodes in the neck, underarm, stomach, or groin.
• Feeling very tired.
• Pain or fullness below the ribs.
• Fever and infection.
• Weight loss for no known reason.

Tests that examine the blood, bone marrow, and lymph nodes are used to detect (find) and diagnose chronic lymphocytic leukaemia.

The following tests and procedures may be used:

• Physical exam and history: An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient’s health habits and past illnesses and treatments will also be taken.
• Complete blood count (CBC): A procedure in which a sample of blood is drawn and checked for the following:
o The number of red blood cells, white blood cells, and platelets.
o The amount of haemoglobin (the protein that carries oxygen) in the red blood cells.
o The portion of the blood sample made up of red blood cells.

• Cytogenetic analysis: A test in which cells in a sample of blood or bone marrow are viewed under a microscope to look for changes in the structure or number of chromosomes in the lymphocytes.
• Immunophenotyping: A test in which the cells in a sample of blood or bone marrow are looked at under a microscope to find out if malignant lymphocytes (cancer) began from the B lymphocytes or the T lymphocytes.
• Bone marrow aspiration and biopsy: The removal of a small piece of bone and bone marrow by inserting a needle into the hipbone or breastbone. A pathologist views both the bone and bone marrow samples under a microscope to look for abnormal cells.

Certain factors affect treatment options and prognosis (chance of recovery).

Treatment options depend on:

• The stage of the disease.
• Red blood cell, white blood cell, and platelet blood counts.
• Whether there are symptoms, such as fever, chills, or weight loss.
• Whether the liver, spleen, or lymph nodes are larger than normal.
• The response to initial treatment.
• Whether the CLL has recurred (come back).

The prognosis (chance of recovery) depends on:

• Whether there is a change in the DNA and the type of change, if there is one.
• Whether lymphocytes are spread throughout the bone marrow.
• The stage of the disease.
• Whether the CLL gets better with treatment or has recurred (come back).
• Whether the CLL progresses to lymphoma or prolymphocytic leukaemia.
• The patient's general health.

Stages of Chronic Lymphocytic Leukaemia

Key Points for This Section

• After chronic lymphocytic leukaemia has been diagnosed, tests are done to find out how far the cancer has spread in the blood and bone marrow.
• The following stages are used for chronic lymphocytic leukaemia:
o Stage 0
o Stage I
o Stage II
o Stage III
o Stage IV

After chronic lymphocytic leukaemia has been diagnosed, tests are done to find out how far the cancer has spread in the blood and bone marrow.

Staging is the process used to find out how far the cancer has spread. It is important to know the stage of the disease in order to plan the best treatment. The following tests may be used in the staging process:

• Bone marrow aspiration and biopsy: The removal of a small piece of bone and bone marrow by inserting a needle into the hipbone or breastbone. A pathologist views both the bone and bone marrow samples under a microscope to look for abnormal cells.
• Chest x-ray: An x-ray of the organs and bones inside the chest. An x-ray is a type of energy beam that can go through the body and onto film, making a picture of areas inside the body, such as the lymph nodes.
• MRI (magnetic resonance imaging): A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body, such as the brain and spinal cord. This procedure is also called nuclear magnetic resonance imaging (NMRI).
• CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerised tomography, or computerised axial tomography.
• Blood chemistry studies: A procedure in which a blood sample is checked to measure the amounts of certain substances released into the blood by organs and tissues in the body. An unusual (higher or lower than normal) amount of a substance can be a sign of disease in the organ or tissue that produces it.
• Antiglobulin test: A test in which a sample of blood is looked at under a microscope to find out if there are any antibodies on the surface of red blood cells or platelets. These antibodies may react with and destroy the red blood cells and platelets. This test is also called a Coomb's test.

The following stages are used for chronic lymphocytic leukaemia:

Stage 0

In stage 0 chronic lymphocytic leukaemia, there are too many lymphocytes in the blood, but there are no other symptoms of leukaemia. Stage 0 chronic lymphocytic leukaemia is indolent (slow-growing).

Stage I

In stage I chronic lymphocytic leukaemia, there are too many lymphocytes in the blood and the lymph nodes are larger than normal.

Stage II

In stage II chronic lymphocytic leukaemia, there are too many lymphocytes in the blood, the liver or spleen is larger than normal, and the lymph nodes may be larger than normal.

Stage III

In stage III chronic lymphocytic leukaemia, there are too many lymphocytes in the blood and there are too few red blood cells. The lymph nodes, liver, or spleen may be larger than normal.

Stage IV

In stage IV chronic lymphocytic leukaemia, there are too many lymphocytes in the blood and too few platelets. The lymph nodes, liver, or spleen may be larger than normal and there may be too few red blood cells.

Refractory Chronic Lymphocytic Leukaemia

Refractory chronic lymphocytic leukaemia is cancer that does not get better with treatment.

Treatment Option Overview

Key Points for This Section

• There are different types of treatment for patients with chronic lymphocytic leukaemia.
• Five types of standard treatment are used:
o Watchful waiting
o Radiation therapy
o Chemotherapy
o Surgery
o Monoclonal antibody therapy

• New types of treatment are being tested in clinical trials. These include the following:
o Chemotherapy with stem cell transplant

There are different types of treatment for patients with chronic lymphocytic leukaemia.

Different types of treatment are available for patients with chronic lymphocytic leukaemia. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. Before starting treatment, patients may want to think about taking part in a clinical trial. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment.

Clinical trials are taking place in many parts of the country. Information about ongoing clinical trials is available from the NCI Web site. Choosing the most appropriate cancer treatment is a decision that ideally involves the patient, family, and health care team.

Five types of standard treatment are used:

Watchful waiting

Watchful waiting is closely monitoring a patient’s condition without giving any treatment until symptoms appear or change. This is also called observation. During this time, problems caused by the disease, such as infection, 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. There are two types of radiation therapy. External radiation therapy uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer. The way the radiation therapy is given depends on the type and stage of the cancer being treated.

Chemotherapy

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping the cells from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the spinal column, an organ, or a body cavity such as the abdomen, or the drugs mainly affect cancer cells in those areas (regional chemotherapy). The way the chemotherapy is given depends on the type and stage of the cancer being treated.

Surgery

Splenectomy is surgery to remove the spleen.

Monoclonal antibody therapy

Monoclonal antibody therapy is a cancer treatment that 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 in the body that may help cancer cells grow. The antibodies attach to the substances and kill the cancer cells, block their growth, or keep them from spreading. Monoclonal antibodies are given by infusion. They may be used alone or to carry drugs, toxins, or radioactive material directly to cancer cells.

New types of treatment are being tested in clinical trials. These include the following:

Chemotherapy with stem cell transplant

Chemotherapy with stem cell transplant is a method of giving chemotherapy and replacing blood-forming cells destroyed by the cancer treatment. Stem cells (immature blood cells) are removed from the blood or bone marrow of the patient or a donor and are frozen and stored. After the chemotherapy is completed, the stored stem cells are thawed and given back to the patient through an infusion. These reinfused stem cells grow into (and restore) the body’s blood cells.

Treatment Options by Stage

Stage 0 Chronic Lymphocytic Leukaemia

Treatment of stage 0 chronic lymphocytic leukaemia is usually watchful waiting.
Stage I, Stage II, Stage III, and Stage IV Chronic Lymphocytic Leukaemia

Treatment of stage I, stage II, stage III, and stage IV chronic lymphocytic leukaemia may include the following:

• Watchful waiting when there are few or no symptoms.
• Monoclonal antibody therapy.
• Chemotherapy with 1 or more drugs, with or without steroids or monoclonal antibody therapy.
• Low-dose external radiation therapy to areas of the body where cancer is found, such as the spleen or lymph nodes.
• A clinical trial of monoclonal antibodies with or without chemotherapy.
• A clinical trial of chemotherapy and monoclonal antibody therapy with stem cell transplant.

Treatment Options for Refractory Chronic Lymphocytic Leukaemia

Treatment of refractory chronic lymphocytic leukaemia may include the following:

• A clinical trial of chemotherapy with stem cell transplant.
• A clinical trial of a new treatment