Chronic myeloid leukaemia (CML)

• What is Chronic Myeloid Leukaemia
• Statistics on Chronic Myeloid Leukaemia
• Risk Factors for Chronic Myeloid Leukaemia
• Progression of Chronic Myeloid Leukaemia
• Symptoms of Chronic Myeloid Leukaemia
• Clinical Examination of Chronic Myeloid Leukaemia
• How is Chronic Myeloid Leukaemia Diagnosed?
• Prognosis of Chronic Myeloid Leukaemia
• How is Chronic Myeloid Leukaemia Treated?
• Chronic Myeloid Leukaemia References

What is Chronic Myeloid Leukaemia

Chronic Myeloid Leukaemia usually arises from the precursors of 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. It is necessary to understand the different types of cell found within the bone marrow.

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.

Statistics on Chronic Myeloid Leukaemia

It is relatively uncommon and occurs in approximately 1 in 100,000 people, rarely affecting those below the age of 20 and usually occurring in the 40-50 year age group, with sex incidence being slightly more common in males.

Geographically, the tumour is found worldwide.

Risk Factors for Chronic Myeloid Leukaemia

The characteristic feature of CML is the presence of certain genetic translocation in affected stem cells in the bone marrow – the translocation between chromosomes 9 and 22 (9;22)(q34;q11) – the so called Philadelphia chromosome. This translocation is believed to be the cause of the unchecked proliferation of the stem cells, with further chromosomal transformations important for further progression of the disease.

The only real predisposing factor for this type of leukaemia is exposure to high doses of radiation such as that caused by nuclear accidents. Most cases occur with no obvious cause. Cigarette smoking has been shown to accelerate the progression to blast crisis.

Progression of Chronic Myeloid Leukaemia

This type of tumour spreads by expansion within the marrow space and the marrow of the bones in the body.

How is Chronic Myeloid Leukaemia Diagnosed?

General investigations may show anaemia or low platelet count. The peripheral white blood cell count can vary between 50-200 x 10/9 per litre. The peripheral blast count is less than 10% in the chronic phase.

Prognosis of Chronic Myeloid Leukaemia

Chronic myeloid leukaemia can be quite variable in terms of its natural history. The relatively stable chronic phase of this leukaemia averages approximately 4 years. Having said that, some patients have had prolonged chronic phases of more than 15 years, although this is much less common.

Following the chronic phase, an accelerated phase, sometimes called transformation can occur, with the development of a rapidly increasing number of blasts in the peripheral circulation. Once this occurs, survival is normally between 2 and 6 months.

How is Chronic Myeloid Leukaemia Treated?

The exact treatment given can depend upon the initial white cell count. Initial treatment may be with single agent chemotherapy such as Hydroxyurea or Busulphan.

Younger patients with the disease may be suitable for bone marrow transplantation.

There are a number of newer targeted biological therapies which are showing promise for the treatment of chronic myeloid leukaemia. Interferon can be used and has a reasonable response rate. Specific tyrosine kinase inhibitors can also have an excellent result. More details will follow: visit www.virtualcancercentre.com for updates and comments.

Improvement in symptoms is an important measurement. Specific monitoring may be by measurement of the peripheral white blood cell count. If transformation is thought to have taken place, the peripheral blast count will rise to greater than 15% of the circulating white cell count and bone marrow examination can confirm the presence of a large number of blasts.

The symptoms that may require attention are infection, bleeding and anaemia.

Anaemia may be treated with blood transfusion. 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.

Pain from massive enlargement of the spleen can cause visceral pain and if infarction of the spleen occurs and the peritoneum becomes irritated, somatic pain can also ensue.

Information on other types of leukaemia:

• Promyelocytic leukaemia
• Multiple myeloma
• Myelodysplastic syndrome
• Chronic cymphocytic leukaemia
• Acute lymphoblastic leukaemia
• Acute myeloid leukaemia

Chronic Myeloid Leukaemia References

1. Braunwald, Fauci, Kasper, Hauser, Longo, Jameson. Harrison’s Principles of Internal Medicine. 15th Edition. McGraw-Hill. 2001

 

• Cotran RS, Kumar V, Collins T. Robbins Pathological Basis of Disease Sixth Ed. WB Saunders Company 1999.
• Kumar P, Clark M. Clinical Medicine. Fourth Ed. WB Saunders, 1998.