What is Chronic Lymphocytic Leukaemia

Leukaemia is the name for a cancer where there is a malignant proliferation of stem cells within the bone marrow. Leukaemic blast cells suppress the normal formation of blood cells (haematopoiesis) within the bone marrow and this means that there are not enough of the normal red cells, white cells and platelets in the blood (pancytopaenia) of patients with the disease. It is not known how the leukaemic cells prevent normal haematopoiesis, but the resultant pancytopaenia is responsible for the clinical manifestations of the disease.

Bone marrow is found inside most of the bones in the body. By adulthood, a large proportion of bone marrow has become relatively inactive. Generally speaking, it is the marrow inside the vertebra, ribs and pelvis, which is responsible for producing the blood cells in adults. In times of crisis or when these areas of bone marrow are damaged, marrow activity may switch on in the other bones.

The bone marrow is a collection of cells inside a connective tissue and fatty stroma. It is necessary to understand the different types of cell found within the bone marrow.

Stem cells are the ultimate origin of the other cells. Stem cells differentiate to form 3 main types of ‘progenitor’ cells. Each of these cells is then responsible to produce red cells, white cells and megakaryocytes (which produce platelets).

There are a number of proteins, which stimulate the production of blood cells. These include erythropoietin (EPO), granulocyte-macrophage colony stimulating factor (GM-CSF), granulocyte-CSF (G-CSF), Interleukin 3, 5 and 6 (IL-3, IL-5, IL-6). Generally speaking, these proteins interact with receptors on the surface of the primitive bone marrow cells and stimulate them to produce the adult cells.

Lymphoblasts are normal precursor cells in the bone marrow that differentiate to become mature lymphocytes.

Statistics on Chronic Lymphocytic Leukaemia

Chronic Lymphocytic Leukaemia is the most common form of leukaemia in Western countries with an annual incidence of 3 per 100,000 and occurs primarily as a disease of older patients. The peak age at diagnosis is between 60 and 80 years with sex incidence being a 2:1 male predominance.

Geographically, the tumour is found worldwide, although it is much more common in European countries and the United States than in Asian countries. This difference in incidence is thought to be due to genetic factors.

Risk Factors for Chronic Lymphocytic Leukaemia

The causes of chronic lymphocytic leukaemia (CLL) are not known but several associations have been observed. Genetic factors are thought to play an important role, as evidenced by the strong racial variations in incidence that do not change with migration. These tumours occur with higher incidence in the relatives of patients with the disease.

Chronic lymphocytic leukaemia is the only leukaemia not found to be associated with exposure to ionising radiation.

There is some evidence linking the development of chronic lymphocytic leukaemia to exposure to environmental toxins such as carbon tetrachloride (dry cleaning agent), farm herbicides and solvents used in the rubber manufacturing industries.

Progression of Chronic Lymphocytic Leukaemia

The Chronic Lymphocytic Leukaemia tumour spreads by expansion within the marrow space and the marrow of the bones in the body. The tumour cells are released into the blood and also populate other areas containing lymphatic tissue – most notably the lymph nodes, liver and spleen.

How is Chronic Lymphocytic Leukaemia Diagnosed?

General investigations may show an absolute lymphocytosis with levels usually above 1×10^9 /L. In more advanced cases, anaemia and thrombocytopaenia may be evident.

Prognosis of Chronic Lymphocytic Leukaemia

Chronic lymphocytic leukaemia is the most indolent of all the leukaemias, and yet the prognosis for the disease is highly variable. Up to 30% of patients survive for between 10 and 20 years and their ultimate cause of death is unrelated to their CLL. On the other hand, some chronic lymphocytic leukaemia patients will have a more aggressive course with death within 2 to 3 years. The remainder of patients have an intermediate survival of between 5 and 10 years involving a terminal phase of up to two years associated with considerable morbidity. Although spontaneous regression of the disease has been reported, it is a rare occurrence. The median survival is between 4 and 6 years.

How is Chronic Lymphocytic Leukaemia Treated?

Complete remission in chronic lymphocytic leukaemia is a very rare event and thus treatment of the disease tends to be with palliative rather than curative intent. The disease is very variable in its course and, to date, treatment early in the course of the disease has not been shown to effect long term survival. Indeed, in many instances it is not necessary to commence treatment immediately. For these reasons, it is very important that treatment for the disease is individualised to the patient involved by their treating haematologist.

Treatment options available include chemotherapy, radiotherapy, leukapheresis, splenectomy and bone marrow transplantation. Newer techniques include the use of monoclonal antibodies such as Rituximab and immunotherapy.

Improvement in symptoms is an important measurement. Specific monitoring may be by monitoring the level of lymphocytes and other constituents in the peripheral blood through routine blood testing. An accurate picture of what is happening in the bone marrow can be achieved by a bone marrow aspiration.

The symptoms that may require attention are infection, bleeding and anaemia. Anaemia may be treated with blood transfusion. Patients may require platelet transfusions. Bacterial infections, particularly septicaemia and pneumonia require urgent treatment with intravenous antibiotics. Viral infections can become a particular problem later in the course of the disease.

Care should also be taken to treat more unusual infections such as candida (thrush) in the mouth. Patients suffering from repeated infections may be considered for treatment with intravenous immune globulin (IVIG).

Particularly during chemotherapy, the destruction of the leukaemic cells can produce large amounts of uric acid and prophylactic treatment with Allopurinol is mandatory.

Information on other types of leukaemia:

Chronic Lymphocytic Leukaemia References

Related Documents:

  • For a PPT presentation on CLL titled ‘Mabthera for Chronic Lymphocytic Leukaemia (CLL)’ please click here.
  • To view these PPT slides with a free PowerPoint viewer 2003, please click here.