Introduction
This European APL Platform is committed to bringing you the most up-to-date information about your blood cancer. We know how important it is for you to understand your diagnosis, treatment and support options. With this knowledge, you can work with members of your healthcare team to move forward with the hope of remission and recovery.
Our vision is that one day the great majority of people who have been diagnosed with acute promyelocytic leukemia (APL) will be cured or will be able to manage their disease and have a good quality of life.
Our patient information is for you and for those close to you. It has been developed for and with patients. It is based on the European APL Guidelines and it has been developed by specialists. Our aim is to provide a trusted online resource for APL patients, their family, friends and carers, and APL patient advocacy groups.
This online platform contains general information, and should help answer many of your questions. However, because every person is different, please always listen to the advice of your cancer specialist about your individual treatment.
What is APL
APL is short for acute promyelocytic leukemia. It makes up to 5-15% of all acute myeloid leukemias. Normally, blood cells (red blood cells, white blood cells and platelets) are produced in our bone marrow, the softer spongy part in the middle of our larger bones. APL affects the blood-producing cells, which then start to grow in an uncontrolled and abnormal way. In leukemias, the abnormal cells can spread from the bone marrow out into the bloodstream and to other parts of the body.
APL’s Place in the Leukemia Family
Where APL sits in the leukemia family of diseases is shown in the diagram below:
In short, leukemias can be defined as acute, when they develop quickly, or chronic, when they develop more slowly. Leukemias can also be either lymphoid or myeloid depending on which types of blood-forming cells give rise to the abnormal cells.
Lymphoid type cells normally produce a type of white blood cells known as lymphocytes.
Myeloid type cells normally produce red blood cells (erythrocytes), platelets and some of the other types of white blood cells (basophils, neutrophils, eosinophils, monocytes.)
There are four main types of leukemia (as shown in the diagram) which are named depending on the above factors:
- Acute lymphoblastic leukemia (ALL)
- Acute myeloid leukemia (AML)
- Chronic lymphocytic leukemia (CLL)
- Chronic myeloid leukemia (CML).
APL (acute promyelocytic leukemia) is a sub-type of AML (acute myeloid leukemia). The name tells us that APL develops quickly and affects the myeloid type cells.
The Faulty Gene Causing APL
A gene is a segment of DNA containing the code used to make a protein. A chromosome contains hundreds to thousands of genes. Every human cell contains 23 pairs of chromosomes. APL is caused when parts of chromosomes 15 and 17 swap over (called translocation) and a faulty gene occurs, known as PML/RARA. This is shown in the diagram below:
This faulty gene generates an abnormal fusion protein that increases the number of immature cells (promyelocytes) in the bone marrow.
In APL, the abnormal immature promyelocytes – which would normally mature and develop into infection-fighting white blood cells – don’t mature normally and become cancerous. They expand in the bone marrow so there is not enough room for other normal blood cells to be made in the right quantities. This causes some of the symptoms of APL described below.
Signs and Symptoms of APL
Signs and symptoms of APL tend to be non-specific such as feeling tired, weak, being anemic, having more minor infections than normal and an increased tendency to bleed.
You may also have pancytopenia, which shows up on laboratory testing. This is reduced numbers of the three usual types of blood cells – red blood cells, white blood cells and platelets.
The most common symptoms of APL that people tell us about are discussed below. If they occur together they are known as the “classic triad”. Half of all patients have the “classic triad” when they are diagnosed, and almost all patients have at least one of the three symptoms.
Fatigue
This is due to reduced numbers of red blood cells in the blood, often called anemia. You may feel breathless both with activity and at rest. You may feel constantly tired and unable to exercise. You may also experience chest pain.
Bruising and bleeding
This is due to reduced numbers of platelets in the blood. You may notice you are more prone to bruising. You may find that you bleed more from wounds or have nosebleeds and bleeding gums. You may bleed from your gut, which would cause you to have black tarry stools or bright red blood streaked stools. Some patients may bleed into the brain, causing stroke-like symptoms that result in difficulty in moving parts of the body or difficulty in speaking. The bleeding into the brain may also cause headaches.
Infections and weight loss
This is due to reduced numbers of white blood cells in the blood and can also be due to a high metabolism (burning food quickly). You may have unexplained weight loss, and infections and fever even when there are no signs of an infection.
Treatments
Background
There are no big differences in the way that APL is treated in adults and children. Rarely (1 in 100) people may develop other cancers and blood disorders because of their APL treatment. If APL is left untreated there is a high risk of severe bleeding. Therefore, patients with APL should begin specif treatment immediately.
The goal of treatment is to achieve remission. For the disease to be cleared, two “levels” of remission need to be achieved. The first level is called morphological remission or complete remission. This occurs when less than 5% of the abnormal promyelocytes, are detected in bone marrow so the blood count is considered normal again. The second level of remission is called molecular remission or complete molecular remission. This occurs when APL cells cannot be detected by the most sensitive test available. There is no trace of the PML/RARA gene (assessed from a blood sample of the bone marrow) with the highly sensitive PCR test. This test can detect 1 APL cell among 10 000 normal cells, so it picks up the very few remaining APL cells which may not be visible under a microscope. It is normal not to have a PCR test after the first cycle of treatment; the test is performed after later courses of treatment.
The aggressiveness of APL can vary between patients but we do not know why. Some patients may be cured by their first course of treatment but in others, the disease returns or they develop other forms of leukemia. The current treatment for APL is different than for other sub-types of AML.
FIRST-LINE THERAPY
First-line therapy is the initial treatment course that is given after diagnosis. If it is successful then further treatment is not required. Normally, first-line therapy consists of:
ATRA
You would start taking ATRA as soon as your doctor thinks you may have APL but may stop this if APL is not the confirmed diagnosis. The ATRA that you have already taken will not harm you.
You would take ATRA – the acid form of vitamin A – in the form of a capsule. ATRA does not “kill” the cancerous cells but allows immature cells to mature and the cancerous cells spontaneously die.
Some people may experience side effects when taking ATRA, but these can generally be overcome using dexamethasone – a corticosteroid medication.
ATRA alone can cause disease remission but it is best supported by the addition of another specific agent arsenic trioxide in patients with lower risk disease and by “traditional” chemotherapy in high risk patients.
Anthracyclines
Anthracyclines are a class of chemotherapy drug that damage the DNA’s structure when they merge with the DNA within cells. These drugs are given directly into the vein – intravenously – and work particularly well against cancers. You may start anthracyclines at the same time as ATRA or a few days later.
ATO
Arsenic Trioxide (ATO) is given in conjunction with ATRA. It works in a similar way to ATRA in that it targets a protein made by the PML-RARA gene by inducing its degradation inside the cells. It is normally given intravenously but may become available to take in tablet form.
KEEPING YOU WELL
After your third course of treatment, if your PCR test is negative showing no remaining APL cells in the bone marrow, then you will likely be started on 2-year period of maintenance chemotherapy or you will receive the fourth consolidation course in case of ATRA and ATO therapy.
If you do relapse, you may need further treatment with different drugs. You may also have a stem cell transplant as part of this treatment. Throughout your treatment, your healthcare team can support you and your family.
How to live with APL
The outlook for people with APL is generally better than it is for many other forms of blood cancer, although it still depends on factors like age, general fitness, and the type of APL you have. Up to three quarters of younger, fitter APL patients are treated successfully. Some rare types of APL are more difficult to treat.
Try to look after yourself physically as well as emotionally. Tell your healthcare team about any changes in your condition. Although you may feel tired, try to stay physically active as this can reduce the severity of any symptoms. This may be challenging as the tiredness related to the disease and treatment is not the same as “normal” tiredness, which usually improves with sleep and rest. Be careful not take in germs through foods because your immune system is not working as well as it should. You should also have a flu vaccination each year. Avoid live vaccines, such as measles, shingles, oral polio and yellow fever though. If you are taking, or thinking of taking any complementary therapies tell your healthcare team.
You may feel very emotional when you are first told you have APL but your healthcare team will provide you with the comfort, help and support you need. They can also provide you with information to help you deal with both the physical and emotional impact it may have on you, your family and your friends.