About acute promyelocytic leukaemia (APML)
In APML, immature abnormal neutrophils (a type of white blood cell) known as promyelocytes accumulate in the bone marrow. These immature cells are unable to mature and function like healthy mature white cells. The accumulation of these immature cells in the marrow inhibits normal cell production, which results in lower numbers of blood cells circulating the body.
APML is most commonly associated with a swapping over (translocation) of chromosomes 15 and 17. This causes parts of a gene from each of these chromosomes to join and create a fusion gene called PML/RARA. In some cases, other chromosomes may translocate and cause a variant APML, but this is quite rare.
How common is APML?
Less than 100 cases of APML are diagnosed in Australia each year.
Who gets APML?
Age is not a significant factor as there is a fairly constant rate of diagnosis across all age groups after the age of 10. APML equally affects both men and women.
Causes of acute promyelocytic leukaemia (APML)
In most cases the causes of APML remain largely unknown but it is thought to result from damage to one or more of the genes that normally control blood cell development. Factors that may put some people at an increased risk include exposure to:
- prior chemotherapy or radiotherapy, although the risk of developing APML following treatment for prior cancer is rare. When it does occur, it is referred to as treatment-related APML.
- bone marrow disease. People with prior diseases of the bone marrow have an increased risk of developing secondary APML. Generally however, those with pre-existing bone marrow disorders develop AML.
There appears to be no increased risk of developing APML as a result of environmental or occupational hazards.
Symptoms of acute promyelocytic leukaemia (APML)
The main symptoms of APML are caused by a lack of normal blood cells. Because APML develops quickly, people usually report feeling unwell for only a short period of time (days or weeks) before they are diagnosed. Common symptoms include:
- persistent tiredness, dizziness, paleness, or shortness of breath when physically active due to a lack of red blood cells or anaemia
- frequent or repeated infections and slow healing, due to a lack of normal white cells, especially neutrophils
- increased or unexplained bleeding or bruising, due to a very low platelet count, or problems with the clotting system.
Serious bleeding abnormalities due to the low platelet count and clotting factors are much more frequent in patients with APML compared with ‘standard’ AML. Patients often present with increased bruising and bleeding from gums or their bowels, and are at an increased risk of bleeding in their brain.
Occasionally people have no symptoms at all and APML is diagnosed during a routine blood test. Some of the symptoms described may also be seen in other illnesses, including viral infections, so it is important to see your doctor so that you can be examined and treated properly.
Diagnosis of acute promyelocytic leukaemia (APML)
APML is diagnosed by examining samples of your blood and bone marrow.
Full blood count
The first step in diagnosis is a simple blood test called a full blood count (FBC) or complete blood count (CBC). This involves a sample of blood from a vein in your arm being sent to the laboratory for investigation. Many of the white blood cells may be abnormal promyelocytes or leukaemic blast cells and the presence of these abnormal cells suggest you have APML. An APML diagnosis needs to be confirmed by examining the cells in your bone marrow.
Bone marrow examination
If the results of your blood tests suggest that you might have APML, a bone marrow biopsy may be required to help confirm the diagnosis. A bone marrow biopsy involves taking a sample of bone marrow, usually from the back of the hip bone, and sending it to the laboratory for examination under the microscope. The bone marrow biopsy may be done in the haematologist’s rooms, a clinic, or a day procedure centre and is usually performed under local anaesthesia with sedation given either by tablet or through a small drip in your arm. The sample of bone marrow is examined in the laboratory to determine the number and type of cells present and the amount of haemopoiesis (blood forming) activity taking place there. The diagnosis of APML is confirmed by the presence of an excessive number of blast cells in the bone marrow.
Further testing
Once the diagnosis of APML is made, blood and bone marrow cells are examined further using special laboratory tests. These include immunophenotyping and cytogenetic tests. These tests provide more information about the exact type of disease you have, the likely course of your disease and the best way to treat it.
Other tests
Tests may be conducted to provide information on your general health and how your vital organs are functioning. These include a combination of further blood tests and imaging tests such as x-rays, scans and ECGs. Blood tests that check clotting times within the blood will also be performed. These results will provide a baseline for your disease and general health, which will be compared with later results to assess how well you are progressing and responding to treatment.
Treatment of acute promyelocytic leukaemia (APML)
The treatment for APML differs from the treatment of other types of acute leukaemia because it involves the use of a “retinoid” drug, which is not a chemotherapy drug; it is actually a derivative of vitamin A, which works by making the immature promyelocytes (the identifiable leukaemic cells in APML) mature properly. This drug is now used in combination with standard chemotherapy to induce a remission, and has improved survival rates for people diagnosed with APML.
The first cycle of treatment a patient receives is called induction therapy. In most cases you will need to be admitted to hospital for induction chemotherapy.
At the time of diagnosis of APML a patient is at high risk of side effects resulting from clotting and bleeding problems. In general, these risks are greatest during the first two to four weeks, and increase the need to commence treatment urgently if a diagnosis of APML is suspected. Patients with APML have an increased risk of developing Disseminated Intravascular Coagulation. This is a serious condition in which clots form in blood vessels, causing a decrease in the production of clotting factors and thereby increasing the risk of bleeding. Blood tests monitoring clotting factors and platelet counts will be conducted frequently to ensure intervention can be undertaken if bleeding problems arise.
Further cycles of chemotherapy will be given after the initial induction treatment. This is called consolidation therapy and can last for up to two years, and is an important part of minimising the chances of the APML returning (relapse). Although not routinely used, stem cell transplants may sometimes be considered for patients who have relapsed after initial induction therapy.
Generally speaking the prognosis for APML is better than other types of acute leukaemia, however individual general health and history plays a role. Your specialist will discuss all treatment options and their side effects and benefits with you prior to commencing treatment.
Please note that the treatments described above are for patients who have the PML-RARA fusion gene present in their APML. Treatments for the less common subtype differ significantly.
Side effects of APML treatment
All treatments can cause side effects. However, the type and severity will vary between individuals, depending on the type of treatment used and how an individual responds to it. In general, more intensive treatment is associated with more severe side effects. It is important to report any symptoms you are having to your doctor or nurse. In most cases they can be treated and are reversible.
When to contact your doctor or hospital
As a general rule, while you are having treatment you will need to contact your doctor or hospital immediately if you experience any of the following:
- a temperature of 38C or higher (even if it returns to normal) and/or an episode of uncontrolled shivering (a rigor)
- bleeding or bruising, for example blood in your urine, faeces, or sputum; bleeding gums, or a persistent nose bleed
- nausea or vomiting that prevents you from eating or drinking or taking your normal medications
- severe diarrhoea, stomach cramps or constipation
- coughing or shortness of breath
- a new rash, reddening of the skin, itching
- a persistent headache
- a new pain or soreness anywhere
- if you cut or otherwise injure yourself
- if you notice pain, swelling, redness or pus anywhere on your body.
What are the side effects of APML treatment?
Effects on the bone marrow
Chemotherapy affects the bone marrow’s ability to produce adequate numbers of blood cells. As a result, your blood count (the number of white cells, platelets and red cells circulating in your blood) will generally fall within a week of treatment. The length of time it takes for your bone marrow and blood counts to recover mainly depends on the type of chemotherapy given.
When your platelet count is very low (thrombocytopenic) you can bruise and bleed more easily. In many cases a transfusion of platelets is given to reduce the risk of bleeding until the platelet count recovers.
If your red blood cell count and haemoglobin levels drop you will probably become anaemic. When you are anaemic you feel more tired and lethargic than usual. If your haemoglobin level is very low, your doctor may prescribe a blood transfusion.
Risk of infection
The point at which your white blood cell count is at its lowest is called the nadir. This is usually expected 10-14 days after having your chemotherapy. During this time you will be at a higher risk of developing an infection. At this stage you will also be neutropenic, which means that your neutrophil count is low.
Neutrophils are important white blood cells that help us to fight infection. While your white blood cell count is low you should take sensible precautions to help prevent infection. These include avoiding crowds, avoiding close contact with people with infections who are contagious (for example colds, flu, chicken pox) and only eating food that has been properly prepared and cooked. If you do develop an infection you may experience a fever, which may or may not be accompanied by an episode of shivering where you shake uncontrollably. Infections while you are neutropenic can be quite serious and need to be treated with antibiotics as soon as possible. Sometimes your doctor may decide to use a drug to help the recovery of your neutrophil count. This drug works by stimulating the bone marrow to increase the production of neutrophils and is usually given as an injection under the skin (subcutaneous).
Nausea and vomiting
Nausea and vomiting are often associated with chemotherapy and some forms of radiotherapy. These days however, thanks to significant improvements in anti-sickness (anti-emetic) drugs, nausea and vomiting are generally very well controlled. You will be given anti-sickness drugs before and for a few days after your chemotherapy treatment. Be sure to tell the nurses and doctors if the anti-emetics are not working for you and you still feel sick. Some people find that eating smaller meals more frequently during the day, rather than a few large meals, helps to reduce nausea and vomiting. Many find that eating cool or cold food is more palatable, for example jelly or custard. Drinking ginger ale or soda water and eating dry toast may also help if you are feeling sick.
Changes in taste and smell
Both chemotherapy and radiation therapy can cause changes to your sense of taste and smell. This is usually temporary but in some cases it lasts up to several months.
Mucositis
Mucositis, or inflammation of the lining of the mouth, throat or gut is a common and uncomfortable side effect of chemotherapy and some forms of radiotherapy. It usually starts about a week after the treatment has finished and goes away once your blood count recovers, usually a couple of weeks later. During this time your mouth and throat could get quite sore. Soluble pain medication and other topical drugs (ones which can be applied to the sore area) can help. If the pain becomes more severe, stronger pain killers might be needed. It is important to keep your mouth as clean as possible while you are having treatment to help prevent infection. Avoid commercial mouthwashes, as these are often too strong or may contain alcohol, which will hurt your mouth.
Bowel changes
Chemotherapy can cause some damage to the lining of your bowel wall. This can lead to cramping, wind, abdominal swelling and diarrhoea. Be sure to tell the nurses and doctors if you experience any of these symptoms. If you are constipated or if you are feeling any discomfort or tenderness around your anus when you are trying to move your bowels, you may need a gentle laxative to help soften your bowel motions.
Hair loss
Hair loss is unfortunately a very common side effect of chemotherapy and some forms of radiotherapy. It is, however, usually only temporary. The hair can start to fall out within a couple of weeks of treatment and tends to grow back three to six months later. Avoiding using heat or chemicals and only using a soft hairbrush and a mild baby shampoo can help reduce the itchiness and scalp tenderness which can occur while you are losing your hair. You need to avoid direct sunlight on your exposed head (wear a hat) because chemotherapy and radiotherapy makes your skin even more vulnerable to the damaging effects of the sun (like sunburn and skin cancers). Remember that without your hair your head can get quite cold so a beanie might be useful. Hair can also be lost from your eyebrows, eyelashes, arms and legs.
Fatigue
Most people experience some degree of tiredness in the days and weeks following chemotherapy and radiotherapy. Getting plenty of rest and doing a little light exercise each day may help to make you feel better during this time. It is important to listen to your body and rest when you are tired.
Fertility
Some types of chemotherapy and radiotherapy may cause a temporary or permanent reduction in your fertility. If possible, before you commence treatment you should discuss any questions or concerns you might have regarding your future fertility with your doctor. In women, some types of chemotherapy and radiotherapy can cause varying degrees of damage to the normal functioning of the ovaries.
In men, sperm production can be impaired for a while but the production of new sperm may become normal again in the future. There are some options for preserving your fertility, if necessary, while you are having treatment for leukaemia.
Parotitis
Associated with radiotherapy, parotitis is an inflammation of the saliva-producing glands in the mouth, which can occur if these glands are within the treatment field used. These include the parotid or submandibular glands, which are situated at the top of the jaw line, in front of the ears. Parotitis causes dryness of the mouth and jaw pain, which usually settles down within a few days, once the inflammation subsides.
Early menopause
Some cancer treatments can affect the normal functioning of the ovaries. This can sometimes lead to infertility and an earlier than expected onset of menopause, even at a young age. The onset of menopause in these circumstances can be sudden and, understandably, very distressing. Hormone changes can lead to many of the classic symptoms of menopause. Some women experience decreased sexual drive, anxiety and even depressive symptoms during this time. It is important that you discuss any changes to your periods with your doctor or nurse.
Body image, sexuality and sexual activity
Hair loss, skin changes and fatigue can all interfere with how you feel about yourself as a man or a woman and as a ‘sexual being’. During treatment you may experience a decrease in libido and it may take some time for things to return to ‘normal’. It’s perfectly reasonable and safe to have sex while you are on treatment or shortly afterwards, but there are some precautions you need to take. It is usually recommended that you or your partner do not become pregnant as some of the treatments given might harm the developing baby. As such, you need to ensure that you or your partner use a suitable form of contraception. Condoms are also necessary in the seven days following a treatment session, to ensure that your partner is not exposed to any residual drugs. Partners are sometimes afraid that sex might in some way harm the patient. This is not likely as long as the partner is free from any infections and the sex is relatively gentle.
Caring for someone with acute promyelocytic leukaemia (APML)
We have a range of information and resources that may help when you are caring for someone with acute promyelocytic leukaemia (APML).
