Acute Promyelocytic Leukaemia (APL)

APL is rare type of acute myeloid leukaemia (AML). It is also called APML or AML M3. 

Blood cells and leukaemia

To understand how and why leukaemia affects you as it does, it helps to know how you make blood cells.

Your body makes blood cells in the bone marrow. The bone marrow is the soft, spongy tissue in the inner part of your bones. You make blood cells in a controlled way, as your body needs them. This continuous supply keeps your blood healthy and your body functioning properly.

All blood cells start as the same type of cell, called a stem cell. This stem cells can turn into any type of blood cell. The stem cells can develop into:

• myeloid stem cells 
• lymphoid stem cells

Myeloid stems cells become monocytes, red blood cells, platelets and white blood cells called granulocytes. Neutrophils are one type of granulocyte.

Lymphoid stem cells develop into white blood cells called lymphocytes. Examples include B lymphocytes and T lymphocytes.

The simplified diagram below helps to explain this.

In acute myeloid leukaemia, the bone marrow makes too many monocytes or granulocytes. These cells are not fully developed and are not able to work normally.

Symptoms and diagnosis

In APL, the levels of red blood cells, white blood cells, and platelets are low. This is called pancytopenia. This can cause:

• infections

• tiredness

• bruising and bleeding

You may also have some weight loss. 

Your GP will usually arrange for you to have a blood test if you have these symptoms. They may then refer you to a specialist if your blood test results are abnormal or your GP suspects you have APL.

Seeing a specialist and further tests

A specialist in blood disorders is called a haematologist. Your specialist will take a sample (biopsy) of your bone marrow. They look at the cells under a microscope to check for leukaemia cells. 

You will also have other tests on bone marrow and blood samples to look for any genetic changes.

APL is confirmed through genetic tests. Most people with APL have a genetic change or fault called PML and RARA fusion. There are at least 16 other possible gene changes or faults. PML and RARA fusion is the most common.  

PML and RARA are the names of genes . In APL, part of the PML gene breaks off from chromosome  15 and attaches to the RARA gene on chromosome 17. The medical name for this is translocation. These stick together (fuse) which causes the PML::RARA fusion. This fusion is a mistake that causes cancer cells to develop. This gene change is something that happens in your lifetime rather than something you have inherited or runs in families.

Knowing whether you have this fusion can also help your specialist decide on the best treatment for you.

Treatment options for APL

APL can develop very quickly so you will start treatment straight away usually before all of your test results are back. Treatment aims to get rid of all signs of APL. This is known as remission.

You are looked after in a specialist hospital by a healthcare team who are used to treating people with APL. You stay in hospital for your first treatment. Your team carefully monitor you when you start treatment and until you are safe to go home.

The main treatment for APL is tretinoin (also called ATRA or all-trans-retinoic-acid). Tretinoin belongs to a group of drugs called retinoids, they are similar to vitamin A. You take tretinoin as tablets. You might start taking this if your doctor suspects that you have APL. This often starts before all your test results are back.

If you start treatment and if your diagnosis changes after further tests, you will stop taking tretinoin. The tretinoin you have already taken will not do any harm.

You have a combination of tretinoin with one or two chemotherapy drugs. The most common treatments are:

• tretinoin and arsenic trioxide

• tretinoin, idarubicin and mitroxantrone

You have some of these drugs into a vein (intravenously) and some as tablets. Your healthcare team can explain this to you in more detail.

Treatment risks groups

Treatment for APL depends on the risk group. This refers to a low, intermediate or high risk of the cancer coming back after treatment. The number of white blood cells help doctors decide which risk group you are in.

Low or intermediate risk APL

You have tretinoin and arsenic trioxide.

High risk APL

Treatment for people who are fit and well enough to cope with the side effects of intensive treatment have AIDA. This is tretinoin, idarubicin, and mitoxantrone chemotherapy.

Treatment is different for people who are not that fit and well, or you have other health conditions. For example, heart or lung problems. You have tretinoin with or without low dose chemotherapy.

Phases of APL

APL treatment is divided into different phases. These are called induction, consolidation and maintenance. Not everyone has all phases. This depends on your risk group.

Induction

The aim of the induction phase is to destroy as many leukaemia cells as possible.

Consolidation

This phase aims to get rid of any leukaemia cells that might still be there and to reduce the risk of the leukaemia coming back.

Maintenance

Maintenance treatment aims to help keep the leukaemia away (in remission). People with low to intermediate APL don’t have maintenance treatment. But some high risk people might have maintenance.

Supportive therapies 

APL can cause your blood cells to drop to very low levels. You usually need treatment to help correct this and relieve symptoms. Some of these supportive treatments include replacing (transfusing) low levels of substances in your blood through a drip. These might include:

• red blood cells if the level of your red blood cells is low

• platelets if your platelet count is low

• fresh frozen plasma (FFP) to help stop you from bleeding – this is the fluid part of blood. It contains essential proteins and clotting factors

• cryoprecipitate to help stop you from bleeding- this is made from FFP and is a more concentrated.

Other supportive treatments include:

• antibiotics to help prevent or treat infections

• anti sickness medicine to help prevent or relieve feeling or being sick

Side effects of APL treatment

The side effects of APL treatment will vary from person to person. Not everyone gets these side effects, but you are closely monitored when you have this treatment.

We have detailed information about the side effects of treatment on each cancer drug page.

A common side effect of taking ATRA or arsenic trioxide is differentiation syndrome. You might also hear it called retinoic acid or ATRA syndrome. It can happen anytime from when you start treatment with ATRA to up to several weeks into treatment. It can be mild or potentially be life threatening. Symptoms can include:

• high temperature (fever) of unknown cause

• weight gain

• fluid build up in your hands, arms, legs and feet (peripheral oedema)

• shortness of breath

• chest pain

• dry cough

• low blood pressure that can cause you to feel lightheaded or dizzy

• not passing enough wee

• feeling confused

• tiredness and weakness

• feeling sick

You might have a steroid called dexamethasone to try and prevent differentiation syndrome from happening. Whether you have this depends on your white blood cell count at diagnosis.

If you develop differentiation syndrome while on treatment you start treatment with dexamethasone. You may also need other treatment to help you such as:

• oxygen if you are breathless

• medicine to help get rid of any extra fluid you may have

• transfusions of blood, platelets and substances that help your blood to clot

Your doctor might also start another treatment called hydroxyurea if your white blood count gets very high. You can usually continue your APL treatment if your symptoms improve with the steroids and hydroxyurea.

If there isn’t any improvement or you become extremely unwell, you might have to pause your treatment until your symptoms improve. You will then be able to re start your treatment once it is safe to do so.

If APL comes back or doesn't go away

If your APL comes back (relapses) or doesn’t go away (refractory), you usually have more treatment. This depends on treatment you have already had. For example, if you had tretinoin with arsenic trioxide as your first treatment, you might have tretinoin with another chemotherapy. If you had tretinoin and chemotherapy, you might have tretinoin and arsenic trioxide.

Some people may have a stem cell transplant, but this is less common. A transplant allows you to have high doses of chemotherapy and other treatments such as radiotherapy to the whole body (TBI).

This treatment helps destroy leukaemia cells. But it also destroys your healthy stem cells in the bone marrow too. To recover you have healthy stem cells through a drip from a donor. This is called an allogeneic transplant. If you are unable to have an allogeneic transplant or there is no suitable donor available you might have your own stem cells to replace blood cells. This is called autologous stem cell transplant.

After you have the healthy stem cells they find their way back to your bone marrow where they start making blood cells again.

Research and clinical trials

Researchers continually look for ways to improve treatment. There may be fewer clinical trials for rare sub-types of leukaemia such as APL. But you can ask your healthcare team if there is anything suitable for you.  

A large group of researchers in the UK are carrying out a series of trials for people with AML. This includes people with APL.

The AML 19 trial is following people with APL who are having treatment with tretinoin and idarubicin. As well as looking at the results of treatment, it is also asking people about their quality of life. 

Coping

Treatment for most people with APL is successful. But coping with the news you have cancer can be difficult, both practically and emotionally. Being well informed about your cancer and its treatment can make it easier to make decisions and cope with what happens.

Talking to other people who have the same thing can also help. As APL is rare, you may not meet other people with exactly the same type of AML to you. In this situation, national organisations and their forums might be useful.

Our discussion forum Cancer Chat is a place for anyone affected by cancer. You can share experiences, stories and information with other people who know what you are going through.

Blood Cancer UK have information about APL, as well as a support phone service and a community forum.

The Rare Cancer Alliance offer support and information to people affected by rare cancers.