About acute promyelocytic leukaemia (APML)
Acute promyelocytic leukaemia (APML) develops when a genetic change affects how immature blood cells grow.
In most people with APML, parts of chromosomes 15 and 17 swap places. This leads to the promyelocytic leukaemia (PML) gene and the retinoic acid receptor a (RARa) gene joining.
The PML-RARa gene stops immature white blood cells from developing normally. These cells do not grow into healthy white blood cells, so they cannot fight infection well. The abnormal cells grow quickly and crowd the bone marrow, leaving less room to make healthy blood cells.
Symptoms of acute promyelocytic leukemia (APML)
The symptoms of acute promyelocytic leukaemia (APML) are similar to acute myeloid leukaemia (AML). Some of the more common symptoms include:
- tired for no reason
- dizziness
- breathlessness
- general weakness
- unexplained fever or infection
- easy bruising or bleeding
- low mood.
Disseminated intravascular coagulation (DIC) is a serious problem that can happen when you have acute promyelocytic leukaemia (APML). In DIC, your body’s clotting system is switched on by mistake. This causes many small blood clots to form.
Blood clots can block blood vessels. This can cause:
- deep vein thrombosis (DVT) – a blood clot in a deep vein in your body
- pulmonary embolism (PE) – a blood clot from a deep vein, in most cases from your leg, that travels to the lung and blocks blood flow to your lungs.
These clots use up lots of platelets, which are needed to stop bleeding. This can lead to severe and uncontrolled bleeding. Severe bleeding can lead to breathing problems or organ failure.
If DIC is not treated, it can be life threatening.
DIC happens more often in APML, but it can also happen in any type of AML.
Causes of acute promyelocytic leukaemia (APML)
Acute promyelocytic leukaemia (APML) is associated with a specific genetic change which is also called a mutation. In most cases, there is no specific reason for the change. Some factors that can increase your risk of developing APML include:
- age – it is more common among people over 40
- previous chemotherapy or radiotherapy
- previous bone marrow disease
- Hispanic ethnicity
- obesity
- exposure to dangerous chemicals.
Risk categories for acute promyelocytic leukaemia (APML)
Acute promyelocytic leukaemia (APML) is categorised into risk groups. This helps your treatment team predict your prognosis and plan your treatment. Your risk group is based on your white blood cell count at diagnosis.
Low to intermediate risk APML is defined by a white blood cell count of less than 10 billion cells per litre of blood at diagnosis.
High risk APML is defined by a white blood cell count of more than 10 billion cells per litre of blood at diagnosis.
Subtypes of acute promyelocytic leukaemia (APML)
The main subtype of acute promyelocytic leukaemia (APML):
- is APML with the gene mutation called t(15;17) (q24.1;q21.2) PML-RARa
- accounts for 95% of all cases.
The second most common subtype of APML:
- is APML with the gene mutation called t(11;17) (q23;q21) ZBTB16-RARa
- accounts for 2% of all APML
- often has a poorer prognosis than the main subtype of APML.
There are also a very small number of people who have APML with other RARa gene rearrangements, where the RARa gene joins with a different gene.
Diagnosis of acute promyelocytic leukaemia (APML)
Acute promyelocytic leukaemia (APML) is diagnosed with a number of tests:
Genetic tests look for changes or mutations in cancer cells. These tests help identify APML from other acute myeloid leukaemia (AML) subtypes.
Genetic tests include:
- FISH (fluorescence in situ hybridisation)
- PCR (polymerase chain reaction).
They are done from blood and bone marrow, so you don’t need to do an extra test.
Blood tests are taken:
- at diagnosis and throughout treatment
- to check how APML is affecting your blood cells and to monitor your electrolytes and organs such as your liver and kidneys
- to look for genetic changes that can help confirm the diagnosis and monitor your response to treatment.
If your haematologist thinks you have APML, you will have a full blood count (FBC) with a differential. This measures the number of red blood cells, white blood cells and platelets, as well as the different types of white blood cells. It may also show abnormal immature cells called blasts in your blood.
A bone marrow biopsy may be done if your haematologist thinks you have APML.
A bone marrow biopsy uses a needle to take a sample of bone marrow, usually from the back of the hip. A small amount of liquid bone marrow is removed and sent to the lab for testing. This includes genetic tests. Often, a tiny piece of the bone itself is also taken to be examined. A bone marrow biopsy helps confirm the diagnosis of APML.
Other tests you may have include:
- medical history and physical examination
- chest x-ray
- heart and lung tests
- ultrasound
- computed tomography (CT) scan.
These tests may be done before or during treatment to check your general health and look for complications. They may also be used if you develop symptoms or concerns that need further investigation.
Fertility and acute promyelocytic leukaemia (APML)
Treatments for acute promyelocytic leukaemia (APML) can affect fertility.
For women some treatments can cause damage to the ovaries.
For men it is possible to have low or abnormal sperm production.
Your fertility may become normal again in the future, but it is difficult to predict.
It is important to ask your doctor about your risk of infertility as early as possible, and discuss your options for preservation of fertility in detail.
There are some options, however, APML is a very aggressive cancer, and to get the best results, you must start treatment as soon as possible. This means not all options for fertility preservation will be available to you before starting treatment.
Visit our Fertility and blood cancer webpage for more information.
Treatment for acute promyelocytic leukaemia (APML)
Your haematologist will consider many factors when discussing a treatment plan for acute promyelocytic leukaemia (APML) with you, including:
- your risk group
- your overall health
- your age
- your wishes.
Treatment is given in 3 phases:
- Induction aims to get the APML into remission (when symptoms have decreased or are undetectable).
- Consolidation aims to destroy any hiding cells that may have survived induction.
- Maintenance aims to maintain remission, this may not be required in some cases of low risk APML.
Treatment for low to intermediate risk disease includes medicines called differentiating agents. High-risk disease is treated with differentiating agents and chemotherapy.
Differentiating agents are medicines that help immature cancer cells grow into normal blood cells.
All-trans retinoic acid (ATRA) and arsenic trioxide are differentiating agents used to treat APML. They work on the gene change that causes APML and remove the block that stops the cancer cells from maturing. This allows immature cells to develop into normal blood cells. Arsenic trioxide can also cause APML cells to die.
ATRA is taken as a tablet by mouth. Arsenic trioxide is given as an intravenous infusion (also called IV).
Differentiation syndrome
Differentiation syndrome is a serious side effect of differentiating agents. It happens when immature APML cells mature too quickly. It causes inflammation and fluid buildup in the body. Symptoms include:
- fever
- weight gain
- swelling
- breathlessness
- low blood pressure.
You will be monitored for signs of differentiation syndrome when you start these medicines, usually in hospital. If you are at home and develop these symptoms, seek urgent medical help.
Treatment for differentiation syndrome includes medications to reduce inflammation, such as dexamethasone (also known as a steroid). Sometimes other medicines are used to reduce the number of APML cells in the blood, such as hydroxycarbamide (a medicine that kills rapidly growing cells).
Chemotherapy is not usually the main treatment for APML. It may be used with all-trans retinoic acid (ATRA) and arsenic trioxide, depending on your APML risk level and treatment plan. Chemotherapy can damage healthy cells and cause side effects.
Your haematologist will explain which medicines you will have, when you will have them and how often.
Information about chemotherapy side effects and how to manage them is available on our Chemotherapy webpage.
There are several treatment plans for APML. They can be found on the Cancer Institute NSW website.
Clinical trials may be available for some types of APML. They often compare new or combination therapies with current treatments, including side effects.
Many are randomised, meaning some patients receive the new treatment, and others receive standard care. Trials help improve future treatments and may offer access to costly new therapies not on the Pharmaceutical Benefits Scheme (PBS) in Australia.
If you are considering a clinical trial, your doctor will explain:
- the possible risks and benefits
- how it compares to standard treatment
- what is involved.
You will need to give informed consent before taking part.
Survival rate for acute promyelocytic leukaemia (APML)
The survival rate of acute promyelocytic leukaemia (APML) has improved over time, and is now generally greater than 90%, 5 years from diagnosis. Survival rate is a population-based measure. Whereas your individual prognosis takes into account factors that can impact survival rate.
Your prognosis is estimated by your haematologist. It is a prediction of the likely course and outcome of your disease. The factors considered when discussing your prognosis include:
- your APML subtype and stage
- your overall health
- your age
- your ability to manage the treatment.
Your prognosis might change if your APML comes back or does not respond to treatment.
Follow-up care for acute promyelocytic leukaemia (APML)
Follow-up care for acute promyelocytic leukaemia (APML) is likely to include regular checkups with your treatment team. These appointments help monitor your recovery, check for any long-term side effects and look for signs that the APML has returned (known as relapsed). Follow up will include regular blood tests and possibly genetic tests.
Living with acute promyelocytic leukaemia (APML)
Life after a blood cancer diagnosis can be different. Regular appointments, including follow-up care and tests, may be tiring or stressful. Your priorities and everyday life may also change.
You may need support with your:
- physical and emotional wellbeing
- relationships
- exercise and nutrition
- finances and return to work or study.
Everyone responds differently to cancer and treatment. There is no right or wrong way to cope. There are some helpful resources and information to guide you on our Living well with blood cancer webpage.
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).
Resources for APML
Booklet to download:
The AML booklet may be of assitance for you.
Optimal Care Pathway for APML
Although there isn’t a specific Optimal Care Pathway for APML, the Optimal Care Pathway for AML, developed in association with the Cancer Council, Australia may be of assistance and you can access it below.
Your Guide to Best Cancer Care – for acute myeloid leukaemia (AML) patients
A guide to help you, your family, and friends as you navigate through the healthcare system
References
- Acute promyelocytic leukemia: A summary, Journal of the Advanced Practitioner in Oncology
- Acute promyelocytic leukemia, Leukemia Research Foundation
- Acute promyelocytic leukaemia (APL or APML), Cancer Research UK
- Acute promyelocytic leukemia and variant fusion proteins: PLZF-RARα fusion protein at a glance, Seminars in Oncology
- A novel PML::RARA fusion in acute promyelocytic leukemia: A case report and literature review, Frontiers in Oncology
- Charting a course through the acute promyelocytic leukemia (APL)-like nebula: The enigmatic cousins of APL, Haematologica
- Detection of cytogenetically cryptic PML-RARA fusion in acute promyelocytic leukemia by rapid next generation sequencing, Precision Oncology
- Genotypic and phenotypic characteristics of acute promyelocytic leukemia translocation variants, Hematology/Oncology and Stem Cell Therapy
- Risk factors and remaining challenges in the treatment of acute promyelocytic leukemia, International Journal of Hematology
