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Home Cancer Leukemia Chronic Lymphocytic Leukemia (CLL)

Chronic Lymphocytic Leukemia (CLL)

Chronic Lymphocytic Leukemia (CLL) affects the lymphocytes in the blood. Lymphocytes are white blood cells which produce antibodies and which are vital parts of the body’s immune system.

Normal lymphocytes are grouped into several different types with different functions. The two main groups are T and B cells. Very early lymphocytes have not yet committed themselves to become either T or B cells. One type of committed lymphocyte is called the B cell and is an antibody producing cell. The antibodies which B–cells produce help to fight off infections. The other type of committed lymphocyte is the T cell which kills viruses, other infectious organisms and cells which are “foreign” to the body. Most cases of CLL are B–cell in type. The word chronic describes the comparatively sluggish progress of the disease if it is not treated. It has no bearing on the seriousness of the condition or the potential ability to cure the disease.

Many patients with CLL will require little or no treatment. Those who do need treatment can usually be treated effectively with low doses of anti–cancer drugs. There are several stages of CLL. The likely progress of the disease depends on a large number of factors, and only a patient’s own doctor can tell them what the likely prospect is for them. While it may help to read about the illness all patients should also rely on their own doctor for the most reliable information about their treatment and prognosis.

Causes of Chronic Lymphocytic Leukemia
Like all forms of leukemia the cause of most cases of Chronic Lymphocytic Leukemia is unknown. There are no clearly defined risk factors for CLL. Leukemia is not passed on from parent to child.

Exposure to radiation does not appear to be a significant risk factor for CLL. The incidence of CLL varies markedly between different ethnic groups. Asians show a very low incidence of CLL wherever they live in the world. This suggests that there is a genetic variation in risk. Close relatives of CLL patients appear more likely than other people to have some form of cancer of the lymphatic system but it is important to stress that these cancers are still rare in this group. There is currently a study being carried out on the possibility that some families do have a genetic tendency to develop CLL.

Classification
Most cases of CLL are of a type known as B–cell after the type of lymphocyte affected. A small proportion of cases affect the T–lymphocytes. There are several different staging systems for CLL. All of the systems are based on the degree of liver or spleen enlargement, the number of enlarged lymph nodes (glands) and on whether there is anemia or a low platelet count.

The most commonly used system is called the International Working Party classification and runs from A (least affected) to C (most affected). The Rai classification is another staging system and goes from stage 0 (least affected) to stage IV (most affected).

Treatment of Chronic Lymphocytic Leukemia
The stage of the illness is important in deciding which patients require active treatment. Patients with stage A disease do not usually require treatment. They will normally just have a check–up every six months or so. This can be done at their local hospital. When a person develops clinical symptoms the aim of treatment is usually to control the disease. This is called palliative treatment. This normally involves having low doses of drugs which have minimal side–effects. The most common drug used is called Chlorambucil.

When treatment does become necessary the symptoms can usually be controlled fairly easily with low doses of chemotherapy drugs. The low doses used have few side effects and are usually easily tolerated. Patients will normally be given their drugs by mouth and will not need to be admitted to hospital. Most patients on treatment can expect to be maintained free of symptoms. However their disease is still present and can be detected in laboratory tests. Treatment with a relatively new drug called Fludarabine may clear the leukemic cells from the marrow and from the blood. This is called a remission. However, it remains to be established how long remission from Fludarabine treatment will last. Fludarabine is given by infusion (a drip) into a vein daily over a period of several days.

As long as the number of abnormal cells can be kept under control and the spleen is not grossly enlarged patients will have few or no symptoms and can lead a fairly normal life. Patients rarely need to be hospitalized during this phase. Recurring infections may be a troublesome feature during the course of Chronic Lymphocytic Leukemia. This is because of reduced immunity and, in some cases, a low neutrophil count. Injections of gamma–globulin may be given to improve immunity and prompt use of antibiotics is often needed. Vaccination against flu and other problem infections may be considered. Splenectomy, that is removal of the spleen, may be necessary if patients are experiencing discomfort due to an enlarged spleen. Splenectomy is not necessary for most patients, and is reserved for patients whose doctors feel that they are particularly likely to benefit.
Radiotherapy (X–rays) may be useful to deal with swollen lymph glands or spleen if these do not respond to drugs.

Drugs and other treatments
Chlorambucil
Chlorambucil has been the drug of choice for most patients once treatment becomes necessary. This is given by mouth either in small doses daily for several weeks or in bigger doses for three or four days with three to four week intervals between courses.

The patient is able to remain at home and work normally. Chlorambucil reduces the number of leukemia cells in the blood and shrinks the lymph glands and spleen if these are enlarged. It may also temporarily reduce the number of red cells, granulocytes and platelets. Chlorambucil may cause abnormal blood count and so treatment must be monitored with blood tests to ensure that the blood count is normal. Occasionally it causes nausea, vomiting and skin rashes. It does not cause hair loss.

Prednisolone
Another drug that can be given by mouth is Prednisolone. Like Chlorambucil, Prednisolone shrinks the lymph nodes and spleen in patients with CLL. After several weeks of therapy it may also lower the blood lymphocyte count and reduce the number of lymphocytes invading the marrow. Unlike Chlorambucil, Prednisolone does not lower the normal level of red cells, granulocytes and platelets and this can be an advantage in some patients. Chlorambucil does, however, have a number of other potential side–effects, particularly if used for prolonged periods in high doses. These side–effects include a tendency to a raised blood pressure, excess sugar in the blood (diabetes), mood changes, insomnia, indigestion and stomach or duodenal ulcers. Prolonged use may also cause fattening of the face and weakness of the muscles of the arms and legs.

Fludarabine
Fludarabine is a drug which is particularly effective in treating cancers of the lymphoid system such as CLL and lymphoma. Fludarabine is useful in treatment where the original drugs have ceased to be effective. The main side–effects seen with Fludarabine are fever and infection.

Bone marrow transplantation
Most patients with CLL do not require aggressive treatment. For the minority whose disease is more difficult to treat, a bone marrow transplant is rarely an option. This is because CLL is most common in older patients for whom the risks of a bone marrow transplant are very much greater.

Current studies are exploring the possibility of achieving a cure for CLL patients younger than 60 years, using autologous transplantation (transplants done using the patient’s own bone marrow or peripheral blood stem cells).

Prognosis of Chronic Lymphocytic Leukemia
The prognosis, that is the likely outcome of the illness, is good for most patients with Chronic Lymphocytic Leukemia. The majority of patients with Chronic Lymphocytic Leukemia are able to lead a normal or virtually normal life although the condition is not considered to be curable in most patients.

CLL patients who are stage A when diagnosed will need little or no treatment and will live for 10 years or more, often dying of a completely unrelated condition. During this stage patients feel well and lead a normal life. There is some evidence that treating patients in the very early stages may actually reduce the average life–expectancy. If and when symptoms do require treatment this normally only requires mild anti–cancer drugs in low doses.

The medication is normally taken as tablets on an out–patient basis. Most patients with Chronic Lymphocytic Leukemia will never need to be in hospital for treatment of their leukemia. In about 10% of cases of Chronic Lymphocytic Leukemia the condition will gradually change into another form of leukemia resembling Prolymphocytic Leukemia or a Lymphoma.

Many elderly patients with Chronic Lymphocytic Leukemia will enjoy the same life span as if they had never developed the disease. Those patients whose life span is shortened by the disease very rarely suffer distress even in the final stages of the condition. Chest and other infections are common in patients with Chronic Lymphocytic Leukemia and may require prompt treatment with antibiotics. For this reason any patient who develops shortness of breath or a cough, or any other signs of a chest infection, should contact their doctor immediately.

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