Chronic Myelogenous Leukemia

Leukemia is blood cancer. There are different kinds of leukemia and one of them amongst its classification in chronic myelogenous leukemia, also called chronic myeloid leukemia.

Cause of chronic myelogenous leukemia

There is no clear reason why chronic myelogenous leukemia develops. It is believed that an abnormality in chromosomal content of the white blood cells is what results in its
development. This abnormality refers to abnormal fusion in the ‘ABL’ section of
chromosome 9 with ‘BCR’ section of chromosome 22. The resultant chromosome is
called the Philadelphia chromosome, and it a common finding in most patients with chronic myelogenous leukemia.

Philadelphia chromosome

There are a few risk factors that can result in chronic myelogenous leukemia –

1. Advancing age – It is commoner as one gets older.

2. Chemical exposure

3. Radiation exposure

These of course are rare risks and in most cases there is no clear cause identified.

Symptoms of chronic myelogenous leukemia

The symptoms of chronic myelogenous leukemia build up over a period of time, sometimes a few months. Some of the common symptoms include –

  • Generalised fatigue (tiredness)
  • Weight loss
  • Decreased capacity to exercise
  • Low grade fever
  • Bleeding spots (petechiae)
  • Painful bones

In most cases, patients tend not to worry about these symptoms too much and chronic myelogenous leukemia is usually diagnosed when they have a routine blood test. This is because the symptoms take a while to manifest.

On examination, patients may appear a bit pale due to anemia. On examination of the abdomen, the spleen can be significantly enlarged (commonest finding) as can the liver.

This is called hepato-splenomegaly. Patients may have a fever and may be sweaty as well. In patients who experience a fast developing disease (acute phase), bleeding under the skin and bruising may be a sign of chronic myelogenous leukemia. In some cases there may be swelling and bleeding at the back of the eye.

Diagnosis of chronic myelogenous leukemia

As this is a blood disorders, it is natural that chronic myelogenous leukemia be diagnosed from a series of different blood tests and certain special tests.

1. Blood tests – This will reveal a high white blood cell count. On further analysis, a group of cells called granulocytes are increased in number. Normally these cells are able to fight infections and if they are produced in excess and serve no function die off, but this does not happen in chronic myelogenous leukemia. In most cases, these cells are mature but in different stages of chronic myelogenous leukemia these can also be immature ‘blast’ cells. These cells have a unique appearance if a blood smear is examined under the microscope and are positive for Philadelphia chromosome.

2. Bone marrow examination – The bone marrow is the site where blood cells are formed. In chronic myelogenous leukemia, the bone marrow is ‘overpacked’ with cells of different kinds, particularly a type called megakaryocytes. Genetic examination of these cells reveals that they are positive for Philadelphia chromosome as well.

Bone Marrow in CML

Bone marrow is analysed by performing a bone marrow biopsy. This can be a slightly painful procedure and is performed under local anaesthesia in most cases (though it can be performed under general anaesthesia). A small sample of the bone marrow is taken out of the hip bone or the chest bone and analysed under the microscope.

Newer techniques are being developed to analyse blood and bone marrow specimens these days, including a method called Fluorescent In Site Hybridisation (FISH). Detailed discussion on this test is out of the scope of this article.

3. Philadelphia chromosome – This is considered to be characteristic of chronic myelogenous leukemia, but there can be cases where it is not present in the cells. However, its positivity does not confirm a diagnosis of chronic myelogenous leukemia, as it can be positive in conditions such as acute
lymphocytic leukemia.

4. Abdominal ultrasound – This is useful in analysing the liver and the spleen and estimating their sizes.

Treatment

The treatments of chronic myelogenous leukemia depend on the phase the disease is in. Chronic myelogenous leukemia has a number of different phases that correspond to different activity levels of the disease. Here is a brief summary –

  • Chronic phase – This is a phase of chronic myelogenous leukemia where the disease can remain stable or quiet for a while without the patient developing any symptoms. However, this does not mean they do not require treatment. Patients are treated with a drug called Imatinib, which acts by inhibiting and enzyme called tyrosine kinase. Newer agents are now available which are considered a lot stronger such as Nilotinib and Dasatinib.
  • Accelerated phase – In this phase, the leukemia is extremely active and patients can develop symptoms. Imatinib is useful in this phase provided it has not been used before. Other agents used as chemotherapy are now available and are discussed later.
  • Blast phase – This phase is called so because the bone marrow is packed with immature blast cells, making the leukemia can be very active. Treatments are aimed at calming this down to a point where the disease moves to a chronic phase. Imatinib is useful here as well, but most often chemotherapy is used.

Chemotherapy

Commonly used agents include Hydroxyurea and Busulfan. These inhibit white cell production by suppressing the bone marrow. Unfortunately, they are not without side effects and these need to be kept an eye out for.

Allogenic bone marrow transplant

This is also called stem cell transplant and involves transplanting the bone marrow of the patient with that of a matched healthy donor. It appears to be the only treatment that offers a cure. In some cases, it needs to be combined with chemotherapy as well.

Surgery

Here, the spleen is removed as it can be rather painful when enlarged. However, it does not offer a cure and can be associated with higher rate of complications.

Conclusion

Chronic myelogenous leukemia is a form of blood cancer. Treatment options are variable and have to be tailored to individual needs.