Acute myeloid leukaemia (AML)

Classification according to ICCC : I.b (Acute myeloid leukemias)

Definition

Acute myeloid leukaemia (AML) is a malignant clonal disorder of haematopoiesis characterised by a disorder of proliferation and differentiation of granulopoietic progenitor cells, which leads to chromosomal aberrations in stem cells.

Occurrence

Acute myeloid leukaemia (AML) accounts for approximately 15% of childhood leukaemias. Children with genetic syndromes featuring a chromosomal defect (such as the Down syndrome) are at an increased risk of developing AML. Preleukaemic states, such as the aplastic anaemia, myelodysplastic syndrome, or Fanconi's anaemia, can develop into AML.

Symptoms

The clinical presentation of acute myeloid leukaemia (AML) is varied and not very distinctive. Diagnosis is usually based on changes in the blood count, such as the anaemia, leucocytosis, hyperleucocytosis accompanied with pulmonary leukostasis syndrome, or thrombocytopenia. Organomegaly is inconsistent. Bleeding into the skin, mucous membranes and/or organs is typical for AML, resulting from the disseminated intravascular coagulopathy (DIC) and hyperfibrinolysis.

Diagnosis

Diagnosis is based on changes in the blood count, in which multiple types of blood cells are typically affected. The differential contains myeloblasts which can sometimes confirm the diagnosis (Auer rods). Examination of bone marrow aspiration is crucial for the diagnosis: bone marrow from patients with acute myeloid leukaemia is entirely or partly infiltrated with myeloblasts. Coagulopathy is often present, too.

Classification

Acute myeloid leukaemia (AML) is classified into seven subgroups (M1–M7) which are characterised morphologically by the maturation stage of pathological myeloblasts. Diagnosis is based on the morphological examination of bone marrow treated with a panoptic stain, and on the cytochemical examination of blasts focusing on the granulocytic series. Cytometric classification of blasts, accompanied with a cytogenetic and molecular genetic examination of cancer cells, is essential for the diagnosis. Molecular genetic methods can identify a fusion gene (a product of cytogenetic aberration), which determines a more detailed diagnosis, disease prognosis, and the intensity of further treatment. The fusion gene can be also used to monitor the minimal residual disease (MRD), and therefore the quality of disease remission.     

Therapy

Chemotherapy is the basic treatment method. The basic cytostatic drugs used in AML treatment involve cytarabine, anthracycline antibiotics, and etoposide; newer cytostatic drugs derived from the basic ones can also be used. The importance of biological therapies and monoclonal antibodies (Mylotarg®) has been rising recently. Allogeneic transplantation of stem cells can be recommended for the treatment of high-risk patients in their first remission, or in cases of disease recurrence.

Treatment outcomes

When treatment is done in compliance with the current protocols, long-term remission is achieved in more than 60% of patients. The proportion of relapses ranges between 15 and 25 per cent. This type of leukaemia is also characterised by a higher risk of death during treatment as a result of drug toxicity (death after induction therapy or during remission).

Role of general paediatrician

The general paediatrician plays a crucial role in the first steps of the diagnostic process. The diagnosis itself is established in a haemato-oncological centre. The general paediatrician is subsequently involved in taking care of the patient on maintenance therapy, and has an important role in distinguishing potential late effects of treatment.