Incidence

Acute lymphoblastic leukaemia (ALL) is the most common form of childhood malignancy and primarily affects younger patients. The peak incidence is in individuals aged 4 years old.

Less than 25% of cases occur in patients over 15; there is a second peak in incidence associated with advancing age, which occurs slightly more in males.

Geographically, the tumour is found worldwide. ALL is more common in Caucasian 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 the disease. There is a strong monozygotic twin concordance. Children with Down syndrome have a 15-fold increase in risk of developing ALL. ALL is also associated with Swachman, Kleinfelter and Bloom syndromes, as well as ataxia telangiectasia.

Environmental factors have also been associated with the disease. Maternal exposure to ionising radiation during pregnancy is associated with a 2-fold increase in risk. 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 ALL.

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.

Microscopic Features

The bone marrow can be seen to be filled with large quantities of immature white cells (blasts). The cells can be seen to have coarse and clumped chromatin within the nuclei. The blasts stain negative with Sudan black or myeloperoxidase (in contrast to the blasts of acute myeloid leukaemia (AML)).

Differentiation between AML and ALL is not always possible on morphological grounds and most tumours will be analysed for expression of surface markers. More than 80% of cases of ALL are B-cell in origin. Almost 60% of patients will have abnormalities in the karyotype (the chromosomes) of the tumour cells – varying from too many chromosomes to translocations such as the Philadelphia chromosome (9;22) (common in CML).

Peripheral blood. Large blasts with convoluted nuclei and basophilic cytoplasm. (T-ALL phenotype).

Natural History

Cancer cells spread from their origin – which is the blood-forming tissue of the bone marrow – to other parts of the body where blood travels.

Clinical History

Symptoms of ALL result from a lack of one or more of the three main components of blood – red blood cells, white blood cells, and platelets. Lack of red cells causes anaemia, which in turn causes fatigue, weakness, shortness of breath and swelling of the ankles. Lack of mature, functional white cells results in infection, especially within the mouth or skin. More common is a tendency to bleed from lack of platelets. Nose bleeds, bleeding from the gums or easy bruising may be seen.

Clinical Examination

Examination of the patient may show bruising or petechiae. Oral thrush may be present and there may be signs of bleeding from gums or obvious mouth ulceration. Splenomegaly or hepatomegaly may be present, but is less common than seen in acute lymphoblastic leukaemia. Anaemia may be present.

General Investigation

General investigations may show anaemia, leucopaenia and/or thrombocytopaenia.

Specific Investigations

More specific investigations may show leukaemic infiltrates on biopsy of skin lesions. Bone marrow aspirations are diagnostic. Apart from the microscopic changes described above, special immuno-chemistry testing may allow sub-classification of the type of leukaemia.

Prognosis

More than 90% of children with acute lymphoblastic leukaemia will achieve complete remission, of whom more than 60% 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 dismal.

Treatment Overview

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 treatment, it is common for patients to receive consolidative treatment that is usually 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 can be treated with blood transfusions. 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:

Regimens Used in the Treatment of This Disease:

Treatments Used in This Disease:

Non-chemotherapeutic Drugs Used in the Treatment of This Disease:

References

  1. Canadian Cancer Society [online]. Disease progression of acute lymphocytic leukaemia [cited 20 September 2018]. Available from: URL link