Acute lymphoblastic leukaemia is a cancer of blood-forming cells in the bone marrow. Abnormal immature white blood cells (lymphoblasts) fill the bone marrow and spill into the bloodstream. Production of normal blood cells is affected causing anaemia, bleeding problems and infections. Children with acute lymphoblastic leukaemia have a good chance of a cure with treatment.
This leaflet is part of our series on Leukaemia
What is leukaemia?
Leukaemia is a cancer of cells in the bone marrow (the cells which develop into blood cells).
Cancer is a disease of the cells in the body. There are many types of cancer which arise from different types of cell. What all cancers have in common is that the cancer cells are abnormal and do not respond to normal control mechanisms. Large numbers of cancer cells build up because they multiply 'out of control', or because they live much longer than normal cells, or both.
With leukaemia, the cancerous cells in the bone marrow spill out into the bloodstream. There are several types of leukaemia. Most types arise from cells which normally develop into white blood cells. (The word leukaemia comes from a Greek word which means 'white blood'.) If you develop leukaemia it is important to know exactly what type it is. This is because the outlook (prognosis) and treatments vary for the different types. Before discussing the different types of leukaemia it may help to know some basics about normal blood cells and how they are made.
What is normal blood made up of?
- Blood cells, which can be seen under a microscope, make up about 40% of the blood's volume. Blood cells are divided into three main types:
- Red cells (erythrocytes). These make blood a red colour. Red cells contain a chemical called haemoglobin. This binds to oxygen and takes oxygen from the lungs to all parts of the body.
- White cells (leukocytes). There are different types of white cells which are called neutrophils (polymorphs), lymphocytes, eosinophils, monocytes and basophils. They are part of the immune system. Their main role is to defend the body against infection.
- Platelets. These are tiny and help the blood to clot if you cut yourself.
- Plasma is the liquid part of blood and makes up about 60% of the blood's volume. Plasma is mainly made from water but contains many different proteins and other chemicals, such as hormones, antibodies, enzymes, glucose, fat particles, salts, etc.
When blood spills from your body (or a blood sample is taken into a plain glass tube) the cells and certain plasma proteins clump together to form a clot. The remaining clear fluid is called serum.
The bone marrow, stem cells and blood cell production
Blood cells are made in the bone marrow by 'stem' cells. The bone marrow is the soft spongy material in the centre of bones. The large flat bones, such as the pelvis and breastbone (sternum), contain the most bone marrow. To make blood cells constantly you need a healthy bone marrow. You also need nutrients from your diet, including iron and certain vitamins.
Stem cells are immature (primitive) cells. There are two main types in the bone marrow - myeloid and lymphoid stem cells. These derive from even more primitive common 'pleuripotent' stem cells. Stem cells constantly divide and produce new cells. Some new cells remain as stem cells and others go through a series of maturing stages ('precursor' or 'blast' cells) before forming into mature blood cells. Mature blood cells are released from the bone marrow into the bloodstream.
- Lymphocyte white blood cells develop from lymphoid stem cells. There are three types of mature lymphocytes:
- B lymphocytes make antibodies which attack infecting germs (bacteria), viruses, etc.
- T lymphocytes help the B lymphocytes to make antibodies.
- Natural killer cells which also help to protect against infection.
All the other different blood cells (red blood cells (erythrocytes), platelets, neutrophils, basophils, eosinophils and monocytes) develop from myeloid stem cells.
You make millions of blood cells every day. Each type of cell has an expected lifespan. For example, red blood cells normally last about 120 days. Some white blood cells (leukocytes) last just hours or days, whereas some last longer. Every day millions of blood cells die and are broken down at the end of their lifespan. There is normally a fine balance between the number of blood cells that you make and the number that die and are broken down. Various factors help to maintain this balance. For example, certain hormones in the bloodstream and chemicals in the bone marrow called 'growth factors' help to regulate the number of blood cells that are made.
The main types of leukaemia
- Acute lymphoblastic leukaemia (ALL).
- Chronic lymphocytic leukaemia (CLL).
- Acute myeloid leukaemia (AML).
- Chronic myeloid leukaemia (CML).
There are various 'subtypes' of each of these. In addition there are some other rare types of leukaemia. The word:
- 'Acute' means the disease develops and progresses quite quickly.
- 'Chronic' means persistent or ongoing. When talking about leukaemia the word chronic also means that the disease develops and progresses slowly (even without treatment).
- 'Lymphoblastic' and 'lymphocytic' mean that an abnormal cancerous cell is a cell that originated from a lymphoid stem cell.
- 'Myeloid' means that an abnormal cancerous cell is a cell that originated from a myeloid stem cell.
The rest of this leaflet is only about acute lymphoblastic leukaemia (ALL). See separate leaflets called Leukaemia - A General Overview, Acute Myeloid Leukaemia, Chronic Myeloid Leukaemia and Chronic Lymphocytic Leukaemia.
What is acute lymphoblastic leukaemia (ALL)?
ALL is a condition where the bone marrow makes large numbers of abnormal immature lymphocytes. The immature cells are called lymphoblasts. There are various subtypes of ALL. For example, the abnormal lymphoblasts can be immature B or T lymphocytes. The abnormal lymphoblasts continue to divide and multiply but do not mature into proper lymphocytes. Typically, ALL develops quite quickly (acutely) and rapidly becomes worse (over a few weeks or so) unless treated.
Who develops acute lymphoblastic leukaemia (ALL)?
ALL can occur at any age, but about 6 in 10 cases occur in children. It is the most common form of leukaemia to affect children (although it is an uncommon disease). It occurs in about 450 children in the UK each year. It can occur at any age in childhood but most commonly develops between the ages of 4 and 7 years. Boys are more commonly affected than girls.
It is less common in adults. It affects around 200 adults in the UK each year. The average age of an adult with ALL is 55 years.
What causes acute lymphoblastic leukaemia (ALL)?
A leukaemia is thought to start first from one abnormal cell. What seems to happen is that certain vital genes which control how cells divide, multiply and die are damaged or altered. This makes the cell abnormal. If the abnormal cell survives it may multiply out of control and develop into a leukaemia.
In most cases of ALL, the reason why an immature lymphocyte becomes abnormal is not known. There are certain risk factors which increase the chance that leukaemia will develop. However, these only account for a small number of cases. Risk factors known for ALL are high-dose radiation (for example, previous radiotherapy for another condition) and exposure to the chemical benzene.
Some genetic conditions can increase the risk of having ALL in the future. The most common is Down's syndrome. Genetic means that the condition is passed on through families through special codes inside cells called genes.
ALL is not an inherited condition and does not run in families.
What are the main symptoms and problems when acute lymphoblastic leukaemia (ALL) develops?
As large numbers of abnormal lymphoblasts are made, much of the bone marrow fills with these abnormal cells. Because of this, it is difficult for normal cells in the bone marrow to survive and make enough normal mature blood cells. Also, the abnormal lymphoblasts spill out into the bloodstream. Therefore, the main problems which can develop include:
- Anaemia. This occurs as the number of red blood cells (erythrocytes) goes down. This can cause tiredness, breathlessness and other symptoms. You also look pale.
- Blood clotting problems. This is due to low levels of platelets. This can cause easy bruising, bleeding from the gums and other bleeding-related problems.
- Serious infections. The abnormal lymphoblasts do not protect against infection. Also, there is a reduced number of normal white blood cells which usually combat infection. Therefore, serious infections are more likely to develop. Depending on the type and site of infection which develops, the symptoms can vary greatly.
The abnormal lymphoblasts may also build up in lymph glands and the spleen. You may therefore develop swollen glands in various parts of the body, particularly in the neck and armpits, and develop an enlarged spleen. Other common symptoms include an enlarged liver, pain in the bones or joints, persistent high temperature (fever) and weight loss. Without treatment, ALL usually leads to death within a few months.
How is acute lymphoblastic leukaemia (ALL) diagnosed and assessed?
A blood test
A blood test can often suggest the diagnosis of ALL. The test will typically show a low number of red blood cells (erythrocytes), normal white blood cells (leukocytes) and platelets. The blood test also typically shows a number of abnormal lymphoblasts which are not normally seen in the blood. So, the total white cell count in the blood sample may be high, even though the number of normal white cells is low. Further tests are usually done to confirm the diagnosis.
A bone marrow sample
For this test, a small amount of bone marrow is removed by inserting a needle into the pelvic bone, or sometimes the breastbone (sternum). Local anaesthetic is used to numb the area. Sometimes a small core of marrow will also be taken (a trephine biopsy). The samples are put under the microscope to look for abnormal cells and are also tested in other ways. This can confirm the diagnosis. See separate leaflet called Bone Marrow Biopsy and Aspiration for more details.
Cell and chromosome analysis
Detailed tests are done on abnormal cells obtained from the bone marrow sample or blood test. These find out the exact type of cell that is abnormal - for example, if the abnormal cells are immature B lymphocytes or immature T lymphocytes. The chromosomes within the cells are checked for certain changes.
Chromosomes are the parts in the cell which contain DNA - the genetic make-up of the cell. In some cases of ALL, changes can be detected to parts of one or more chromosome. (These changes in chromosomes only occur in the leukaemia cells, not the normal body cells.) For example, in one abnormality called Philadelphia chromosome, a part of chromosome 9 is found to be moved and attached to part of chromosome 22. See separate leaflet called Genetic Testing for more details.
This test collects a small amount of fluid from around the spinal cord (cerebrospinal fluid, or CSF). It is done by inserting a needle between the bones of the back (vertebrae) in the lower (lumbar) region of the back. By examining the fluid for leukaemia cells, it helps to to find out if the leukaemia has spread to the brain and spinal cord. See separate leaflet called Lumbar Puncture for more details.
Various other tests
A chest X-ray, further blood tests and other tests are usually done to assess your general well-being.
What is the treatment for acute lymphoblastic leukaemia (ALL)?
The aim of treatment is to kill all the abnormal cells. This then allows the bone marrow to function normally again and produce normal blood cells. The main treatment is chemotherapy, sometimes combined with radiotherapy. Stem cell transplant (SCT) is sometimes performed.
The exact treatment regime used in each case (the medicines used, doses, length of treatment, etc) takes into account various factors. This is based on research trials which aim to determine the best treatment for the various subtypes of ALL. Research trials continue to try to find even better treatments. The factors which are taken into account include:
- The exact type of ALL (for example, if it is a T-cell or B-cell type).
- If the leukaemia cells contain chromosome changes such as the Philadelphia chromosome.
- Your age, sex and general health.
- The number of lymphoblasts in the blood when your leukaemia was diagnosed.
- How well the condition responds to the initial phase of treatment (see below).
- Whether the leukaemia has spread to the brain and/or spinal cord.
On the basis of these factors, people with ALL are classed as 'low', 'standard' or 'high' risk. That is, the risk of the leukaemia coming back (relapsing) after 'standard' treatment. More intensive treatment is usually offered if your risk is 'high'.
Chemotherapy is a treatment which uses anti-cancer medicines to kill cancer cells, or to stop them from multiplying. See separate leaflet called Chemotherapy with Cytotoxic Medicines for more details.
As many doses of these medicines are likely to be given straight into a vein (intravenously) over a prolonged period, it is usual for a plastic tube to be put into a large blood vessel. This can be a central line in a vein in your chest or a peripheral line in your arm (sometimes called a PICC line). It can be left in place for months until the course of treatment is finished. This means you do not need repeated injections. Medicines can be injected or 'dripped' through the line from time to time when a dose is due.
Chemotherapy for ALL is usually divided into different phases:
- Induction remission phase. This is an initial intensive treatment using a combination of medicines. It lasts about 4-6 weeks. This aims to kill most of the leukaemia cells. At the end of this phase there are usually no leukaemia cells (or fewer than 5%) detectable in a blood sample or seen in a bone marrow sample. This is called being 'in remission'. Remission does not mean cure.
- Consolidation (Intensification) phase. Further medicines are given in this phase of treatment. This aims to kill any remaining leukaemia cells which may still be present (although not detected by any tests). The treatment can be quite intensive, and given in 'blocks' of treatment several weeks apart. The exact medicines used and the intensity can vary, depending on factors such as whether you are in a high-risk, standard-risk or low-risk category.
- Maintenance phase. This phase of treatment is less intensive than the induction and consolidation phases. This phase can last up to two years. The aim of this phase is to kill any remaining leukaemia cells that may have been missed by treatment in the other phases. Maintenance treatment is also given between the blocks of treatment in the consolidation phase.
Treatment of the brain and spinal cord
Abnormal cells sometimes get into the brain and spinal cord. Chemotherapy medicines taken by mouth or injected into the bloodstream do not get into the brain and spinal cord very well. Therefore, chemotherapy medicines are usually injected from time to time over the treatment period directly into the fluid that surrounds the spinal cord and brain. This is done in a similar way to a lumbar puncture (described above) and is called an intrathecal injection. In some cases, radiotherapy to the brain is also used.
Stem cell transplantation (SCT)
SCT - sometimes called bone marrow transplantation - may be performed. It may be used for cases where the leukaemia has come back (recurred) following the usual treatment with chemotherapy. It is also more commonly used for adults with ALL.
Other treatments may include antibiotic or antifungal medicines if infection occurs; blood and platelet transfusions to counter low levels of red blood cells (erythrocytes) and platelets; general supportive measures to overcome side-effects of chemotherapy.
Treatment of relapses
Despite treatment, in up to 1 in 4 cases, the ALL may return (relapse) at some point after treatment. Relapses are treated in a similar way to the initial treatment but the treatment regime is often more intensive.
Side-effects from chemotherapy
Your doctor will advise on the possible risks and side-effects of your particular treatment regime. Very briefly:
Side-effects during treatment
The medicines used for chemotherapy are powerful and often cause unwanted side-effects. The medicines work by killing cells which are dividing and so some normal cells are damaged too. Side-effects vary from medicine to medicine.
The most common side-effects are feeling sick (nausea), loss of hair, and an increased risk of infection (as the normal white blood cells (leukocytes) are affected by treatment). Anti-sickness medicines are commonly used to prevent nausea.
In a small number of cases, problems develop months or years after a period of intensive chemotherapy. For example, some children treated with chemotherapy have problems later in life with puberty and with fertility. There is also a small increased risk of developing a different cancer later in life.
What is the outlook (prognosis)?
Most children with acute lymphoblastic leukaemia (ALL) - about 7-8 in 10 cases - can be cured. The outlook for children has improved greatly over a period of 20 years or so.
Children aged between 1 year and 10 years have the best outlook and are most likely to be cured. The outlook is less good for children aged under 1 year and for children older than 10 years. On average, the outlook for adults is less good than for children but a proportion of adults are cured.
The treatment of cancer and leukaemia is a developing area of medicine. New treatments continue to be developed and the information on outlook above is very general. As mentioned, there are some newer medicines that have been introduced in the last few years and which show promise to improve the outlook. The specialist who knows your case can give more accurate information about the outlook for your particular situation.
The chance of a good response to treatment can vary depending on factors, such as the exact type of ALL
Further help & information
Dr Tim Kenny
Dr Colin Tidy
Dr Adrian Bonsall