This bone marrow blood smear from an AML patient shows the large immature white blood cells. The other smaller cells are red blood cells. — Wikimedia Commons
The blood comprises red blood cells, which transport oxygen; white blood cells, which fight infection; and platelets, which prevent bleeding.
The stem cells in the bone marrow differentiate into myeloid cells, which fight bacterial and parasitic infections, and prevent tissue damage from spreading; and lymphocytes, which fight viral infections.
Leukaemia is cancer of the white blood cells.
It can be acute or chronic. The former progresses rapidly, and the latter, gradually.
Both types are classified according to the type of white cell involved, i.e. acute myeloid and lymphoblastic leukaemia, and chronic myeloid and lymphocytic leukaemia.
Acute myeloid leukaemia (AML) is due to a mutation in the stem cells in the bone marrow, resulting in increased production of mostly immature white blood cells (blast cells) that are unable to combat infections.
There is consequent decrease in the number of normal red blood cells and platelets.
The factors that increase the risk of the mutation include radiation exposure; previous treatment for cancer; benzene found in cigarette smoke and petrol; certain blood disorders like polycythaemia; and genetic disorders like Down syndrome.
However, there are no identifiable risk factors in many AML patients.
Signs and symptoms
The symptoms of AML develop rapidly – usually within a few weeks – and increase in severity as the number of blast cells increase.
They include tiredness; pallor; breathlessness; fever; weight loss; bleeding from various sites like gums, nose and skin; bone and joint pain; frequent infections; and enlargement of the liver and/or spleen.
Rarely, the blast cells spread into the central nervous system causing symptoms like headache, fits and blurred vision.
The complications of AML include weakened immunity, bleeding and infertility.
Weakened immunity is due to either AML itself or the side effects of medicines used in treatment.
This leads to an increased risk of infection and an increased intensity in any infection that develops.
Although all infections respond to early treatment, they are still the leading cause of mortality.
Easy bruising and bleeding from various body sites are common.
The bleeding may be excessive and may occur in the skull, lungs and gastrointestinal tract.
The features are that of the bleeding site, e.g. headache (in the skull), coughing out blood (lungs) and passing out blood in the faeces (gastrointestinal tract).
Bleeding is the second most common cause of mortality.
Temporary or permanent infertility is often a consequence of many treatments.
The latter is more likely in those who have received high doses of chemotherapy and radiotherapy prior to stem cell transplant.
Patients with suspected leukaemia need to have their blood drawn for a full blood count. as in this filepic, which will aid in their diagnosis.
The initial diagnosis of AML is made from blood tests.
An increase in blast cells or a low blood count would lead to a referral to a physician or a specialist in blood conditions (haematologist).
A bone marrow biopsy confirms the diagnosis.
This is carried out under a local anaesthetic in the skin on the back of the hip bone, with a thin needle inserted to remove a sample of bone marrow that is then examined for cancer cells.
If present, the type of leukaemia will be determined.
There may be some bruising and tenderness after the biopsy.
Additional tests are done to detect the extent of AML, which will facilitate decision-making on treatment.
Computerised tomography (CT) scan, x-rays and other tests may be done to assess the patient’s general health.
Genetic tests on blood and bone marrow samples will identify the genetic variations of the cancer cells.
If there is suspicion that AML has spread to the nervous system, a lumbar puncture may be done.
The procedure involves inserting a needle in the back to remove a sample of cerebrospinal fluid to determine if cancer cells are present.
Treatment with chemotherapy
The treatment of AML depends on various factors, including age of the patient, sub-type of AML, general health and preference of the patient or family.
In general, there are two treatment phases.
The objective of the initial induction phase is to destroy as many leukaemia cells in the blood and bone marrow as possible.
However, not all the leukaemia cells can be wiped out in this phase.
As such, the induction phase may have to be repeated.
The objective of the consolidation phase is to decrease the risk of relapse.
Should a relapse occur, repeat(s) of the induction and consolidation phases may be carried out.
This may be the same as the first treatment.
However, it is likely that different medicines will be used.
The treatments used include chemotherapy, radiotherapy, other medicines or stem cell transplant.
Chemotherapy is the primary form of treatment in the induction phase, although it may also be used in the consolidation phase.
The medicines used destroy the leukaemia cells in the blood and bone marrow.
Chemotherapy may be intensive or at a lower dose, depending on the patient’s fitness.
Intensive chemotherapy involves a combination of medicines at high doses given in hospital, as close medical and nursing supervision is needed.
Regular blood transfusions are usually required, as well as a clean environment, due to the increased risk of infection, which is promptly treated if it occurs.
The medicines are injected into a thin tube in a blood vessel in the arm or close to the heart.
In the rare situation where there are leukaemia cells in the nervous system, the medicines are injected through a thin tube placed in the spine.
Side effects are common and temporary.
They include nausea, vomiting, diarrhoea, mouth ulcers, loss of appetite and hair, and infertility, which may be temporary or permanent.
Non-intensive chemotherapy is provided to patients who are not fit to cope with the effects of intensive chemotherapy.
Its objective is to control the leukaemia cells, rather than to cure it.
The medicines may be given into a vein, orally or by injection under the skin. This may be done as an out-patient.
The consolidation phase involves regular injections of chemotherapy medicines, usually given as an out-patient.
Leukaemia patients, as seen in this 2010 filepic, usually wear face masks to avoid infections, which they are prone to.
Radiotherapy with high doses of radiation is done if the leukaemia cells have spread to the nervous system, including the brain, and to prepare for stem cell transplant.
Side effects are common and temporary.
They include nausea, tiredness and hair loss.
Other medicines used include arsenic trioxide and all-trans retinoic acid, which are used alone or in combination with chemotherapy in the induction phase of a subtype of AML called promyelocytic leukaemia.
They cause the leukaemia cells with a specific gene mutation to mature and die, or to stop dividing.
A stem cell transplant may be considered if chemotherapy is ineffective.
The transplant helps the re-establishment of healthy stem cells by placing healthy leukaemia-free stem cells in the bone marrow.
Prior to a stem cell transplant, high dose chemotherapy, and possibly radiotherapy, is given to destroy the leukaemia-producing bone marrow.
Subsequently, infusions from a compatible donor are given through a tube in a vein.
Azacitidine, a chemotherapeutic medicine that destroys cancer cells and helps the bone marrow to produce normal cells, is an alternative for patients who cannot have a stem cell transplant.
Some AML patients choose to enrol in clinical trials involving experimental treatments or new combinations of known treatments.
AML usually requires rapid decision-making about a condition that many may not yet understand.
Coping tips include learning about the condition in the shortest possible time to make healthcare decisions, and relying on family and friends.
Dr Milton Lum is a part president of the Federation of Private Medical Practitioners Associations and the Malaysian Medical Association. The views expressed do not represent that of organisations that the writer is associated with. The information provided is for educational and communication purposes only and it should not be construed as personal medical advice. Information published in this article is not intended to replace, supplant or augment a consultation with a health professional regarding the reader’s own medical care. The Star disclaims all responsibility for any losses, damage to property or personal injury suffered directly or indirectly from reliance on such information.