Acute Lymphoblastic Leukaemia

What is Acute Lymphoblastic 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. This means that there are not enough of the normal red cells, white cells and platelets in the blood (pancytopaenia) of leukaemia patients. It is not known how the leukaemic cells prevent normal haematopoiesis, but the resultant pancytopaenia is responsible for the clinical manifestations of leukaemia. 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 are responsible for producing 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 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 adult cells. Lymphoblasts are normal precursor cells in the bone marrow that differentiate to become mature lymphocytes.

Statistics on Acute Lymphoblastic Leukaemia?

Leukaemia is the most common form of childhood malignancy and occurs primarily as a disease within younger patients. The peak incidence is in individuals aged 4 year olds. Less than 25% of cases occur in patients over 15, but there is a second peak in incidence associated with advancing age, with sex incidence being slightly male predominant. Geographically, leukaemia is found worldwide. Leukaemia is more common in white than black populations. It is less common in Africa and the Middle East than in Europe and the United States.

Risk Factors for Acute Lymphoblastic Leukaemia

The causes of ALL are not known but several associations have been observed. There is a strong familial predisposition with siblings of affected children having a 4-fold increase in risk of leukaemia. There is a strong monozygotic twin concordance. Children with Down syndrome have a 15-fold increase in risk of developing acute lymphoblastic leukaemia. Acute lymphoblastic leukaemia is also associated with Swachman, Kleinfelter and Bloom syndromes, as well as ataxia telengiectasia. Environmental factors have also been associated with leukaemia. Maternal exposure to ionising radiation during pregnancy is associated with a 2-fold increase in risk in the foetus. Other possible maternal associations include increased maternal age, previous miscarriage, and high birth weight. Post-natal exposure to ionising radiation is associated with subsequent development of acute lymphoblastic leukaemia. Viral associations with childhood ALL have been postulated but not as yet proven. The adult T-cell leukaemia/lymphoma is caused by infection with the Human T-cell Lymphoma Virus (HTLV-1) and is endemic in areas of Japan and the Caribbean.

Progression of Acute Lymphoblastic Leukaemia

This type of tumour spreads by expansion within the marrow space and the marrow of the bones in the body.

How is Acute Lymphoblastic Leukaemia Diagnosed?

General investigations may show anaemia, a low white cell count or low platelet count.

Prognosis of Acute Lymphoblastic Leukaemia

More than 90% of children with acute lymphoblastic leukaemia will achieve complete remission. Approximately 60% of individuals who achieve remission, will be alive at 5 years. In patients alive at 5 years, most will have been cured. A poorer prognosis is found in adult patients, in patients with T-cell ALL, or some forms of B-cell ALL. In patients with a chromosomal translocation, prognosis is poorer.

How is Acute Lymphoblastic Leukaemia Treated?

The aim of leukaemia treatment is to destroy the leukaemic cells as completely as possible. Complete remission occurs when the bone marrow returns to a normal balance of red cells, white cells and platelets with less than 5% of blasts. Following induction, it is usual for patients to receive consolidative treatment sometimes followed by maintenance therapy. Certain patients, notably younger patients, may benefit from bone marrow transplantation. A haematologist will be able to advise you as to the suitability of this treatment for you. Improvement in leukaemia symptoms is an important measurement. Specific monitoring may be done by monitoring the level of blast cells in the peripheral blood. An accurate picture of what is happening in the bone marrow can be achieved by a bone marrow aspiration. The leukaemia symptoms that may require attention are

infection
bleeding
anaemia

Anaemia may be treated by blood transfusion. Patients may require platelet transfusions. Bacterial infections due to low neutrophil counts usually require urgent treatment with intravenous antibiotics. Care should also be taken to treat more unusual infections such as candida (thrush) in the mouth. 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: