Bone Marrow Cancer - II

Acute Myeloid Leukaemia

What is Acute Myeloid Leukaemia

Acute Myeloid Leukaemia is a type of leukaemia which arises from the precursors of the myeloid cells which would subsequently, in normal circumstances, evolve into normal white cells. Bone marrow is found inside most of the bones in the body. By adulthood, a large proportion of bone marrow has become relatively inactive. Generally speaking, it is the marrow inside the vertebra, ribs and pelvis, which is responsible for producing the blood cells in adults. In times of crisis or when these areas of bone marrow are damaged, marrow activity may switch on in the other bones. The bone marrow is a collection of cells inside a connective tissue and fatty stroma. Stem cells are the ultimate origin of the other cells. Stem cells differentiate to form 3 main types of 'progenitor' cells. Each of these cells is then responsible to produce red cells, white cells and megakaryocytes (which produce platelets). There are a number of proteins, which stimulate production of blood cells. These include erythropoietin, (EPO) granulocyte-macrophage colony stimulating factor (GM-CSF), granulocyte-CSF (G-CSF), Interleukin 3, 5 and 6 (IL-3, IL-5, IL-6). Generally speaking, these proteins interact with receptors on the surface of the primitive bone marrow cells and stimulate them to produce the adult cells.

Who gets Acute Myeloid Leukaemia?

Acute Myeloid Leukaemia is uncommon and occurs at any time of life, with average incidence of acute myeloid leukaemia being 2.3 per 100,000 people per year. Acute Myeloid Leukaemiausually occurs (80%) in adults with the majority of cases of acute myeloid leukaemia occurring in people over the age of 60, with sex incidence being equal. However, acute myeloid leukaemia can occur in children, especially if there is a predisposition for the leukaemia.

Predisposing Factors

The cause of most cases of acute myeloid leukaemia is unknown. Acute myeloid leukaemia often occurs on the background of another haematological (blood or bone marrow) condition, such as:

  • Myelodysplastic syndromes.
  • Chronic myeloid leukaemia.
  • Myelofibrosis.
  • Polycythaemia rubra vera.
  • Essential thrombocythaemia.
  • Severe aplastic anaemia. Acute myeloid leukaemia also occurs in individuals exposed to:
  • Previous radiotherapy or nuclear irradiation.
  • Previous chemotherapy with alkylating agents or certain other chemotherapy agents and certain organic chemicals such as Benzene and Toluene. Certain individuals may inherit a predisposition to acute myeloid leukaemia such as those with Fanconi's anaemia or Down's syndrome.

Progression

The acute myeloid leukaemia tumour spreads by expansion within the marrow space and the marrow of the bones in the body.








Probable Outcomes

In acute myeloid leukaemia the most important prognostic factor is the attainment of complete remission (CR). This is defined as remission of the leukaemia (evidenced by disappearance of the blast cells) and attainment of near normal platelet and white cell levels. Being of an older age at diagnosis (older than 60) and the presence of medical problems other than the AML also influences prognosis of acute myeloid leukaemia. The duration of the complete remission (CR) and the rapidity with which it is attained are other important factors. Patients are likely to have better prognoses if the blast cells disappear early with treatment, and there is a more prolonged remission. Around 65-75% of patients achieve CR with that chemotherepeutic regime - the others don't because of a drug resistant leukaemia or fatal complications of bone marrow toxicity with the drugs. Infectious complications are the main cause of death.

How is Acute Myeloid Leukaemia Diagnosed?

General investigations (full blood count) may show anaemia (often severe). White cell counts can be low or very high, or just slightly high. More importantly, abnormal leukaemic blast cells are found in more than 95% of patients in peripheral blood. Platelet counts are usually low.

How is Acute Myeloid Leukaemia treated?

Treatment against acute myeloid leukaemia: The aim of acute myeloid leukaemia treatment is to destroy the leukaemic cells as completely as possible and achieve complete remission. Before acute myeloid leukaemia treatment, replacement of various blood components (e.g. platelets, red cells) may be required to prevent bleeding or severe anaemia. Following induction of chemotherapy, it is usual for patients to receive consolidative treatment sometimes followed by maintenance therapy. The usual induction therapy involves cytarabine and an anthracyclene (e.g. daunorubicin). The addition of etoposide or other agents does not increase the CR rate but may increase CR duration. Standard post-remission therapy includes either high dose chemotherapy or stem cell transplantation - patients receive their own stem cells collected while in remission (autologous) or another person's stem cells (allogenic) - the latter has more complications but greater success rate. In the occurrence of a relapse - certain acute myeloid leukaemia patients, notably younger patients, may benefit from stem cell transplantation (from a suitable donor if one is found). This rescues approximately 20% of relapsed patients with AML. Your Haematologist will be able to advise you as to the suitability of this acute myeloid leukaemia treatment for you.

Monitoring: Improvement in acute myeloid leukaemia symptoms is an important measurement. Specific monitoring may be 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.

Acute myeloid leukaemia: Treatment of the Symptoms: The acute myeloid leukaemia symptoms that may require attention are infection, bleeding and anaemia. Anaemia may be treated with blood transfusion. Acute myeloid leukaemia 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:

Acute Myeloid Leukaemia References

  1. Braunwald, Fauci, Kasper, Hauser, Longo, Jameson. Harrison's Principles of Internal Medicine. 15th Edition. McGraw-Hill. 2001
  2. Cotran RS, Kumar V, Collins T. Robbins Pathological Basis of Disease Sixth Ed. WB Saunders Company 1999.
  3. Kumar P, Clark M. Clinical Medicine. Fourth Ed. WB Saunders, 1998.

Regimens Used in the Treatment of This Disease:

Treatments Used in This Disease:

Drugs/Products Used in the Treatment of This Disease:

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