AML

What is AML?

Acute = fast/quick
Myeloid = relating to bone marrow

Acute Myeloid Leukemia (AML) is a disease of the bone marrow in which blood cells are stopped from developing from an early stage resulting in a reduction of normal blood cells. Most AML subtypes show more than 30% blasts of a myeloid lineage in the blood, bone marrow, or both.

Classification of AML

The World Health Organisation (WHO) classification of AML include the following:

• AML with characteristic genetic abnormalities (generally a higher rate of remission and better prognosis):
  1. AML with translocations between chromosome 8 and 21 [t(8;21)].
  2. AML with inversions in chromosome 16.
  3. AML with translocations between chromosome 15 and 17 [t(15;17)].
• AML with multilineage dysplasia (generally worse prognosis):
  1. MDS patients
  2. Myeloproliferative patients
• AML and MDS, therapy-related (generally worse prognosis):
  1. Patients who have had prior chemotherapy and/or radiation.
• AML not otherwise categorized:
  1. Subtypes of AML that do not fit into the above categories.

The French-American-British (FAB) classification system divides AML into eight subtypes:

• M0: acute myeloblastic leukemia, minimally differentiated.
• M1: acute myeloblastic leukemia, without maturation.
• M2: acute myeloblastic leukemia, with granulocytic maturation.
• M3: promyelocytic, or acute promyelocytic leukemia.
• M4: acute myelomonocytic leukemia.
• M4eo: myelomonocytic together with bone marrow eosinophilia.
• M5a: acute monoblastic leukemia.
• M5b: acute monocytic leukemia.
• M6a: acute erythroid leukemia’s, including erythroleukaemia.
• M6b: pure erythroid leukemia.
• M7: acute megakaryoblastic leukemia.

Epidemiology of AML

AML is the most common acute leukemia in adults. It can occur at any age but it is more common in older people (>60 years). AML incidence in European adults is 5-8 cases per 100,000.

Symptoms of AML

A person with AML may suffer from the following:

• Tiredness – This is due to the low levels of hemoglobin in the red blood cells, which carries oxygen to the body.
• Fever and recurring infections – although white blood cells (WBC), which fight infection, may be high, neutrophils are low. Patients might not respond well to antibiotics.
• Bleeding – This is due to low platelet numbers, which prevent bleeding and bruising. This could be excessive bleeding when brushing teeth.

Diagnosis of AML

Diagnosis of MDS is based on the:

• Full blood count
  1. Reduced erythrocytes and thrombocytes.
  2. Total WBC may be normal, high or low, and sometimes extremely high
  3. Neutrophils significantly reduced (and replaced by blasts).
  4. Lactate dehydrogenase levels are usually raised and there may be high levels of uric acid.

• The appearance of the bone marrow
  1. The WHO classification requires more than 20% blasts in the peripheral blood, to make a diagnosis of AML.

• Any chromosome changes found
  1. Some genetic mutations will have a better prognosis than others.

Blood and bone marrow samples are analyzed using specialist tests, which include morphological analysis using microscope imagining, flow cytometry to look at cell shape and size, and cytogenetics to look for genetic mutations. In AML the most common sites for infiltration are the liver and spleen so these sites may be larger than normal.

Management of AML

The treatment type for AML varies based on different factors including age. The first line of management includes blood transfusions, antibiotics for infection and allopurinol to reduce uric acid levels. Then more intensive treatment can begin. The treatment is counted a working when blast levels in the bone marrow are reduced to less than 5%, cells return to their normal morphological structure and peripheral blood cell counts return to normal levels.

• The treatment of AML is usually done in two phases:
• Induction: the aim of this initial stage of treatment is to kill as many leukemia cells in your blood and bone marrow as possible, restore your blood to proper working order and treat any symptoms you may have. This stage may need to be repeated before you move on to the next stage.
• Consolidation – this stage aims to prevent the cancer returning, by killing any remaining leukemia cells that may be present in your body.

The most commonly used drugs that can be used to treat AML for induction therapy include the following:

• cytarabine (Ara C, cytosine arabinoside)
• daunorubicin
• idarubicin (Zavedos®)
• fludarabine (Fludara®)

The most commonly used drugs that can be used to treat AML for consolidation therapy include the following:

• cytarabine
• etoposide
• amsacrine (Amsidine®)
• mitoxantrone

These treatment aims to kill a significant proportion of the abnormal cells in the bone marrow to allow the bone marrow to work normally again (remission). Patients generally need to stay in a hospital for four to six weeks for each course due to high chance of side effects, which may include the following:

• nausea
• vomiting
• diarrhea
• loss of appetite
• sore mouth and mouth ulcers (mucositis)
• tiredness
• skin rashes
• hair loss
• infertility– which may be temporary or permanent

Bone-marrow transplant

A stem cell transplant (or bone marrow transplant) should be considered when there is ‘curative’ therapy is thought to be appropriate. Healthy bone marrow or stem cells are taken from another person whose tissue DNA is identical or almost identical to yours, so the donor is compatible with you.

Before transplantation can take place, the person receiving the transplant will need to have intensive high-dose chemotherapy and possibly radiotherapy to destroy the cells in their bone marrow. The donated stem cells are given through a tube into a blood vessel, in a similar way to chemotherapy medication. The treatment has many side effects and it is important that the decision is thought of carefully.

There are a number of things to bear in mind if opting for this procedure:

• Complicated process with many risks involved.
• Donor match – a donor needs to be identified which can take a while.
• Age is important – younger and fitter suggests a great chance of success.
• Cost – expensive procedure if not provided by the country.

Availability – not all countries support this treatment.