What is leukaemia?
To put it in simple terms, leukaemia is the cancer of the white blood cells. As we know, our blood has three types of cells- red blood cells, white blood cells and platelets. In leukaemia, the white blood cells multiply uncontrollably causing various problems in the body.
What are the types of leukaemia?
There are two main types of acute leukaemia:
- Acute myeloid leukaemia
- Acute lymphoid leukaemia
ACUTE MYELOID LEUKAEMIA: it is a type of leukaemia in which the myeloid cells ae involved. Now, what are myeloid cells? These are cells that are present in the bone marrow or any tissues resembling bone marrow. these include all the blood cells except lymphocytes.
The word “acute” refers to the conditions which progress rapidly to an advanced stage. It becomes potentially fatal from a seemingly normal or mild condition in a very short duration.
What are the risk factors that are associated with acute myeloid leukaemia?
- Preleukaemic disorders: some disorders are predisposed to lead to AML. They are myelodysplastic syndromes and myeloproliferative disease. Some blood disorders also act as a preleukaemic disorder, for example, polycythaemia vera, idiopathic myelofibrosis and thrombocythemia.
- Chemical agents: it is seen that alkylating agents which are used to treat other cancers through chemotherapy may end up causing AML. Agents like epipodophyllotoxins, anthracyclines, procarbazine, chlorambucil, melphalan, busulfan, cisplatin and carboplatin are linked as AML causative agents.
Exposure to chemicals like benzene and formaldehyde through professional hazards can also cause AML. Benzene is a chemical substance that is commonly used as a solvent in rubber industries, oil refineries, shoe manufacturing industries and is also found in motor vehicle exhaust, glues, cleaning products, detergents, art supplies and paints.
- Radiation exposure: exposure to radiation due to atomic bombs, radiation plants, or even radiology labs in high doses can cause mutation of cells leading to AML. It was seen that Japanese atomic bomb accident- Hiroshima and Nagasaki caused its survivors to develop AML, most often 6-8 years after survival.
If a foetus is exposed to radiations in its initial stages of development, it may develop leukaemia, although the extent of the risk factor is not clearly understood.
- Smoking: one of the leading causes of cancer. We know that smoking can cause cancers associated with lungs. But it can also cause dysplastic changes in the blood cells. The toxins from tobacco get absorbed through the lungs and enter the bloodstream causing AML. It is the only proven lifestyle habit that causes AML.
- Genetic disorders: genetic disorders like Fanconi’s anaemia, Bloom syndrome, ataxia-telangiectasia, severe congenital neutropenia, neurofibromatosis type 1 and Li-Fraumeni syndrome may be predisposing factors for AML. Down’s syndrome and trisomy 8 also have a history of AML.
- Family history: if anyone in the family line has a history of AML, the person also has an increased risk, especially if it is his/her own twin who got diagnosed of AML before the age of one.
- Age and sex: although AML can occur in anyone, it is seen with an increased prevalence in older males.
So, what exactly happens in the DNA that causes leukaemia?
To understand what happens to the DNA, we must know what the normal state of the cells is. When the myeloid tissues produce blood cells, it starts out in a stage called “blast” stage. This is an immature cell stage. The cells then are programmed to mature into adult stage where they perform their functions.
Now, our cells know when to divide and when to stop with the help of certain components in the chromosomes (parts of the DNA that decides important functions). The parts that help in initiating division are called oncogenes. The parts which help in killing the cells are called tumour suppressor genes.
When there are some defects in the DNA, due to factors mentioned above, these two parts may get expressed more or less than required. For example, FLT3, c-KIT, and RAS are seen in patients with AML which are oncogenes. They are usually over-expressed and lead to uncontrolled growth of cells.
How can the DNA get mutated?
There are various ways in which defects may creep up into the DNA. Usually, the body destroys these cells, but sometimes, they make their way into the cell cycle and cause havoc in the systems.
- Translocation: when a part of the chromosome breaks off and re-attaches to another part, where it does not belong.
- Deletion: when a part of the chromosome automatically gets removed.
- Addition: when a part of the chromosome gets duplicated multiple times.
- Inversions: when a part of the chromosome gets detached and re-attached in an inverse way.
What are the signs and symptoms of AML?
General symptoms: certain non-specific symptoms which are seen in AML but can also be due to a result of other disorders. These are:
- Weight loss and loss of appetite
- Night Sweats
DUE TO REDUCED RED BLOOD CELLS (anaemia):
- Fatigue: as we know, red blood cells help in transporting oxygen through a substance known as haemoglobin. If the number of red blood cells is reduced, then obviously the oxygen carried to parts of the body will be less and the subsequent energy levels will also be less. As a result, the person feels weak and tired.
- Pallor: this term implies a pale discolouration. It is due to the reduced red cells which leads to a characteristic paleness, especially visible on the mucous membranes and nail beds.
- Dizziness: less oxygen is transported to vital organs like the brain tissues. This leads to dizziness and often, a confused state of mind.
- Shortness of breath: as the amount of energy required by the body is more than the energy received by it, the person faces shortness of breath, as an attempt of the body to increase the amount of oxygen in the blood.
- Cold body temperature: patient frequently complains of feeling cold due to the reduced oxygen content in the blood and reduced energy levels.
DUE TO LOW WHITE BLOOD CELLS (neutropenia):
In case of patients with AML, the white blood cell count is abnormally high, but these cells are rendered useless as they are not capable of protecting the person from infections. The patient might be vulnerable to infections which may become more serious than it actually is or may repeatedly be attached to infections.
DUE TO LOW PLATELET CELLS (thrombocytopenia)
- Increased bleeding of small wounds
- Frequent bruises
- Frequent nosebleeds
- Bleeding of gums
Platelets are needed for the clotting of blood. When the count reduces, it leads to frequent bleeding which may be prolonged, bruises, bleeding spots.
EFFECTS DUE TO INCREASED LEUKAEMIC CELLS:
Leukaemia leads to increased counts of leukocytes or white blood cell. These are of the abnormal immature type which does not perform the functions of healthy white blood cells but instead, take up space in the blood vessels, making the blood thicker. The amount of oxygen is also reduced. This whole condition is termed as leukostasis. This leads to various other problems like:
- Slurred speech
- Bone and joint pain due to a build-up of cells
- Abdominal swelling due to tender spleen and liver from an accumulation of WBC.
- Rashes on the skin (may spread to the skin as chloroma, granulocytic sarcoma, myeloid sarcoma)
- Enlargement and swelling of gums
- Enlargement of lymph nodes (grape sized nodes at specific locations which may be tender)
- Advanced stages can cause seizures, facial numbness, problems with balance
How will the doctor identify AML?
Many tests are performed before the doctor can confirm AML.
- Complete blood picture and blood smear: a few drops of blood is examined under a slide to get a rough count of the number of each type of cells, the shape of the cells, the sizes and other abnormalities that can be detected.
- Blood chemistry: this test measures the values of certain chemicals in the blood and it is checked if they fall within the estimated normal values.
- Coagulation tests: these tests see the rate of blood clotting and bleeding and is useful in estimating the deficiency of platelets.
- Other advanced tests: cytometry, immunohistochemistry, flow cytometry, cytogenetics, fluorescent in situ hybridisation, polymerase chain reaction.
- CT scans: it is only done if the doctor suspects enlargement of spleen and lymph nodes. It is done to estimate the spread of cancer.
- ULTRASOUNDS: these tests are again done to look at growing masses in the other organs.
How is the treatment for leukaemia done?
There are two main stages in the treatment of AML: they are induction and consolidation.
The first stage focuses on reducing the levels of leukemic cells to an undetectable level. Usually, chemotherapy is used. Commonly given drugs are cytarabine with anthracycline. It is called 7+3 therapy as cytarabine is given for seven days continuously and anthracycline for three consecutive days through IV.
The success of this stage is not that the disease is cured but that it cannot be detected in the available diagnostic methods.
the final stage is an intensive chemotherapy focussed on the remnant leukemic cells. This is to prevent remission. Alternatively, the patient can undergo stem cell therapy in severe cases.
Stem cell therapy is also used in patients who have relapsed after primary treatment.
DIFFERENCE BETWEEN ACUTE MYELOID LEUKAEMIA AND ACUTE LYMPHOBLASTIC LEUKAEMIA:
The key difference is the fact that one is a defect from the myeloid cells and the other is a defect from lymphoblastic cells.
AML affects by producing defective blood cells except for lymphocytes. ALL affects by producing excessive amounts of lymphoblasts.
While AML incidence increases with age, ALL is seen in early childhood and older individuals.
The symptoms and treatments tend to be the same in both situations.