Acute Lymphoblastic Leukaemia

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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.

Who gets 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.

Predisposing Factors

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.