ALL or acute lymphocytic leukaemia (previously also termed acute lymphoid leukaemia) is a rapidly progressing malignant tumorous disease (so-called blood cancer) that involves immature progenitor cells from the haematopoietic differentiation pathway that are not fully developed. These immature cells or blasts start to proliferate uncontrollably and are not able to function as mature cells.
Causes and frequency
The cause of ALL is acquired (not hereditary) genetic damage to the DNA of a single bone marrow cell.
This causes:
- an uncontrolled and several times increase in the production of immature non-functional lymphoid line cells or lymphoblasts and their accumulation in the bone marrow; and
- a blockade of the production of normal blood cells (erythrocytes, platelets and normal leukocytes), causing anaemia (shortage of erythrocytes), thrombocytopenia (shortage of platelets) and neutropenia (shortage of neutrophilic granulocytes).
Usually, it is not known what caused the damage to the cell’s genetic material (DNA) that led to leukaemia. There are some known factors which can be associated with increased incidence of leukaemia. Radioactive irradiation and exposure to certain chemicals are some of these factors. Leukaemia is more prevalent in developed countries and among populations with higher socio-economic development. ALL is a rare disease; morbidity is 1-2 primary cases per 100,000 people per year. ALL occurs more often during the first 10 years of life; morbidity also increases with age over 50 years. ALL is one of the most frequent childhood malignant tumours in addition to brain tumours.
Subtypes of acute lymphocytic leukaemia
ALL is divided into several subtypes. During microscopic investigation of leukemic lymphoblasts, they are divided into L1, L2 and L3 subtypes on the basis of cell size and structure. With the help of immunological investigation methods, B-cell and T-cell acute lymphocytic leukaemia are differentiated. 85% of acute lymphocytic leukaemia is B-cell lymphocytic leukaemia. ALL can also be divided on the basis of chromosomal changes leading to leukaemia.
All of these subtypes of acute lymphocytic leukaemia have prognostic value, i.e. one subtype responds more easily to treatment than another and an appropriate treatment regimen should be chosen accordingly.
Symptoms
Most acute lymphocytic leukaemia symptoms are non-specific, i.e. they are present not only in the case of leukaemia but may occur during other diseases. The patients complain of loss of wellbeing, rapid onset of fatigue, breathlessness during physical exercise. Bone and joint pain may occur.
Most ALL symptoms are caused by the reduction of normal blood cell production. Erythrocyte shortage causes anaemia. The patient is pallid, tires quickly during physical exercise, develops breathlessness. Due to the shortage of platelets, a fine spotted rash may occur on skin, even the smallest lesions bleed for a long time, prolonged gum bleeding may occur after brushing teeth and nasal bleeding is also common. Due to the shortage of neutrophils, patients are more susceptible to all kinds of infections; they develop bacterial, viral as well as fungal infections very easily.
In the case of ALL, tumorous lymphocytes may also accumulate in the brain and cerebrospinal fluid, causing headache and nausea, and in the lymphatic system, causing enlargement of lymph nodes.
Diagnosis
Blood and bone marrow should be investigated to diagnose ALL. To obtain bone marrow, the bone must be punctured; in most cases iliac crests are used, in adults also the sternum. The structure of the obtained bone marrow cells is investigated microscopically; immunophenotyping is required to elaborate their origin and genetic tests of bone marrow cells are required to localise chromosomal damage.
Treatment
The medicinal products used for the treatment of ALL are called cytostatics or chemotherapeuticals and the treatment is called chemotherapy. ALL treatment should be started as soon as possible after diagnosis. The aim of the treatment is to achieve a state where there are no more tumour cells in the bone marrow and the production of other normal blood cells has recovered. Such a state is called remission.
In the case of different types of acute leukaemia, different treatment regimens are used which differ by the drugs used, their duration of use and the doses used. The patient’s age and general health status should be taken into consideration when choosing the treatment regimen.
In modern treatment regimens of acute lymphocytic leukaemia, treatment is divided into stages, where the drugs, their administration frequency and the doses are different during each stage, with each stage having a definite role in the treatment regimen used.
The treatment stage with the aim of achieving remission is called induction treatment. If the performed treatment is effective, tumour cells are eliminated from the bone marrow. Thus we make it possible for the normal blood cells to multiply and develop.
When it is no longer possible to identify tumorous cells in the bone marrow, we can talk about remission. But in the case of remission, not all tumour cells have been destroyed in the body; after induction treatment, there are always a certain very small number of so-called residual tumour cells that cannot be identified with our investigation methods. Therefore, treatment should not be stopped immediately when remission is achieved, but the treatment effect should be reinforced and should attempt to destroy the residual leukemic cells. This treatment phase is called the consolidation/intensification phase. In addition to these phases, the treatment regimen contains the maintenance treatment phase aimed at the destruction of tumour cells that have survived the various treatment phases. The maintenance treatment phase is less intense compared with the other phases but is temporally longer. A very important factor of ALL treatment is treatment duration, which may extend up to 2-3 years from the time of diagnosis.
In the case of some types of leukaemia, especially acute lymphocytic leukaemia, the tumorous cells may infiltrate the liquid and membranes surrounding the spinal cord and brain. To avoid this, in the case of these leukaemia types, the chemotherapeutic agent should be administered directly into the cerebrospinal fluid and some medicinal products should be administered intravenously in very high doses. To administer drugs into the cerebrospinal fluid, the spinal canal is punctured between the vertebrae in the lumbar region and the required medicines are administered directly into the cerebrospinal fluid.
In certain cases, an autologous or allogeneic stem cell transplant should be taken into consideration when drawing up a treatment programme.
Compiled by: Dr Ain Kaare
Last updated: 2013