Acute myeloid leukaemia (AML) 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 start to proliferate uncontrollably and are not able to function as mature cells. The cause of AML 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 myeloid line cells or myeloblasts 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. AML is a relatively rare disease; morbidity is 3-4 primary cases per 100,000 people per year and incidence increases with age.
AML subtypes
AML is divided into many subtypes. Morphology, chromosomal changes and gene mutations of leukemic cells are taken into consideration when classifying subtypes. Different subtypes of AML have prognostic value; their treatment is also a little different.
Symptoms
Most acute 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 acute leukaemia 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.
Diagnosis
Blood and bone marrow should be investigated to diagnose acute leukaemia. 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 determine chromosomal damage and gene mutations. These chromosomal changes and gene mutations give important information about disease prognosis and help to choose an optimal treatment programme. Four risk groups are identified in AML.
Treatment
The medicinal products used for the treatment of AML are called cytostatics or chemotherapeuticals and the treatment is called chemotherapy.
Acute leukaemia 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 AML, 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.
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. As a rule, 1-2 induction treatment courses are performed.
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. Such treatment is called consolidating treatment. In the case of AML, 2-3 consolidating treatment courses are performed.
In the case of some types of AML, 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. For this, the spinal canal is punctured between the vertebrae in the lumbar region and the required medicines are administered directly into the cerebrospinal fluid.
As the incidence of AML increases with age, many AML patients are quite old and have lots of concurrent diseases. In such cases, palliative, symptom-alleviating treatment is used for AML with the aim of maintaining quality of life for as long as possible.
The treatment programme for most patients under 65 years of age (excluding the patients belonging to the best risk group) also contains allogeneic blood stem cell transplantation.
Compiled by: Dr Ain Kaare
Last updated: 2013