Acute lymphoblastic leukaemia (ALL) is a condition where the bone marrow makes large numbers of abnormal immature lymphocytes.
What is acute lymphoblastic leukaemia?
Acute lymphoblastic leukaemia (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 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?
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 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 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 makeup 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 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?
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 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?
Most children with ALL - about 7-8 in 10 cases - can be cured. The outlook (prognosis) 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 reading and references
; National Cancer Institute
; European Society for Medical Oncology (Aug 2013)
; Chronic lymphocytic leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015 Sep26 Suppl 5:v78-84. doi: 10.1093/annonc/mdv303.
; European Society for Medical Oncology (2017)
; European Society for Medical Oncology (2015)
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