Video: Professor Anthony Moorman describes what Acute Lymphoblastic Leukaemia is.
Acute Lymphoblastic Leukaemia (ALL) is a blood cancer which affects the lymphocytic cells, which are one type of white blood cell. People will ALL produce too many immature lymphoid cells (blast cells) which populate the blood and bone marrow. Over time, these abnormal cells will accumulate and begin to fill up the bone marrow, preventing it from producing healthy blood cells.
There are several different subtypes of ALL, about three out of every four cases of adult ALL affects B lymphocytes, and is known as B-ALL. Almost all the remaining cases affect T lymphocytes, Similar treatment protocols are used for B-ALL and T-ALL and this information applies to both types.
What causes Acute Lymphoblastic Leukaemia?
In most cases, there is no obvious cause of ALL. But there are certain things which are known to be linked to a high chance of developing this disease.
- Age – Adult ALL incidence increases with age.
- Gender – Men are slightly more likely than women to develop adult ALL.
- Genetic factors – In adults, there is little evidence of genetic risk factors for ALL. There are some known genetic conditions, including Down syndrome, which may be associated with an increased chance of developing ALL. There is no cause for anxiety, or for screening tests, for anyone with a family member who has ALL.
- Environment – Some chemicals and high levels of radiation may increase the chance of developing leukaemia. Strict rules to limit occupational exposure mean that these factors play a very small part in causing ALL in the UK.
- Previous treatment – Some patients can develop ALL after being previously treated with either chemotherapy or radiotherapy. This is uncommon and is called therapy-related ALL. People who develop leukaemia after cancer treatment are more likely to develop a completely different type of leukaemia called acute myeloid leukaemia (AML).
Signs and Symptoms
The majority of patient with ALL will have symptoms when they are diagnosed. However, not everyone experiences all of the symptoms together. Rarely, the condition may be found by chance when a routine blood test is carried out for something else. The most common signs and symptoms are caused by the bone marrow being unable to produce enough normal blood cells.
Symptoms which may be seen include:
- Frequent and recurrent infections
- Fever and night sweats
- Malaise (general feeling of illness)
- Purpura (small purple spots on the skin)
- Unusual bleeding e.g. nose and gums
- Unexplained weight loss
If, after a blood test, ALL is suspected, you will have a set of tests to confirm the diagnosis. If you are diagnosed with ALL, they will also have further tests to determine the right treatment for your cancer.
Sometimes, test results can take a little while. This can be an anxious and worrying time but please remember that it is important that your medical team reach the correct diagnosis so that they can receive the right treatment.
Tests may include:
- Full Blood Count (FBC) – this is a simple blood test which measures the number of red cells, white cells and platelets in the blood. In ALL, there are typically more white cells than normal. Immature blood-forming cells (blasts) are seen in the blood; these are normally only found in the bone marrow.
- Cytogenetics – Cytogenetics is the study of gene changes and investigates the genetic differences between ALL cells and normal cells. Cytogenetic results are important for the WHO classification of ALL and for risk classification.
One of the most important cytogenetic abnormalities is called the Philadelphia chromosome – this forms when parts of chromosomes 9 and 22 are swapped over. The Philadelphia chromosome is most strongly linked to a type of leukaemia called chronic myeloid leukaemia (CML), but can also be seen in other blood cancers, including ALL. The Philadelphia chromosome is much more common in adults with ALL than in children and is associated with poor results using standard treatment. Treatments results can be greatly improved by adding drugs called tyrosine kinases, which were originally developed to treat CML.
- Bone marrow samples – In most cases, your doctor will take a bone marrow sample, where a small amount of bone marrow is taken from the hip bone using a fine needle (an aspirate), to look at the cells. You may also have a sample of bone marrow taken from the core using a larger needle (a trephine) to look at the structure of the bone marrow. This is normally done under local anaesthetic.
Other tests which may be done include:
- Lumbar puncture – in childhood AML, a sample of cerebrospinal fluid (CSF) is taken from the spine to see whether there are leukaemia cells in the nervous system. In AML, cells can get into the nervous system, which protects them from some treatment.
- X-rays, ultrasound or scans (CT or MRI) – To monitor impact on organs of the body.
Blood tests and bone marrow samples will be repeated throughout treatment to monitor response.
The most important part of classifying ALL is risk grouping. There are two risk groups; high risk and standard risk. You should ask your specialist about risk groups and what they mean for your treatment.
It is important to understand that risk groups refer to the outcome using standard treatments. By adjusting treatment according to risk groups the results can be improved.
- High risk – High risk ALL is defined on the basis of age, white cell count, cytogenetics and response to initial treatment, as measured by MRD.
- Standard risk – Standard risk ALL is defined as any patient who does not have high risk features.
What happens next?
Because ALL progresses rapidly, virtually all patients with ALL start treatment soon after diagnosis. You can refuse treatment at any time, but it is important that you understand clearly what might happen in this case. You can always ask for a second opinion at any time. As far as possible, all decisions about treatment will take your wishes into account.
Almost all patients will start treatment at, or soon after, the time of diagnosis. You may be asked to consider taking part in a clinical trial, which is a study comparing treatments to find out which is best. A clinical trial consists of two or more different arms.
If you are not taking part in a trial, your treatment will be based on the current gold standard treatment. Some of the factors considered in treatment planning are:
- Fitness levels and whether or not intensive chemotherapy would do more harm than good.
- Age – your age can affect how well your body responds to treatment.
- Whether there’s a high risk of relapse with standard treatment.
Treatment options for ALL
Initial treatment of ALL usually consists of chemotherapy, and is divided into phases known as induction, intensification, consolidation and maintenance. For younger/fitter patients a stem cell transplant may be considered.
If you may be able to have a stem cell transplant, you will be given detailed information about what this involves.
Induction treatment for adults normally lasts about 8 weeks and uses combinations of drugs.
Patients who are not having a stem cell transplant will have an extended phase of treatment called maintenance. If you are having a stem cell transplant, you will not receive maintenance chemotherapy; the stem cell transplant is done after completion of induction chemotherapy although some patients will receive intensification and consolidation as well before they have their transplant.
You’ll receive your induction treatment as an inpatient in hospital, but you will normally have most of your other treatment as an outpatient. Most patients will need to be admitted to hospital from time to time due to complications such as infection. You’ll be regularly monitored and will probably receive blood and platelet transfusions, if you need them to help support your body.
Chemotherapy is the use of anti-cancer (cytotoxic) drugs to destroy cancer cells. Chemotherapy will also damage some normal cells, which means that there are side effects. In ALL chemotherapy drugs are usually given in combination, you will be given details of your planned treatment and you can ask questions at any time.
The most common cell-killing drugs used to treat adult ALL are:
As well as the cytotoxic drugs, it has been found that steroids are very effective in treatment of adult ALL. The steroids used are artificial versions of natural substances made in your body. It is very important to understand that these steroids are very different from the drugs sometimes abused by athletes or bodybuilders. The steroid most commonly used for treatment of adult ALL is called dexamethasone. Some patients will be given a different steroid, called prednisolone.
For patients who have the Philadelphia chromosome, a type of drug called tyrosine kinase inhibitors are used along with the chemotherapy. These drugs are very effective at preventing the effects of the Philadelphia chromosome.
Immunotherapy uses monoclonal antibodies to attack and destroy ALL cells. Monoclonal antibodies are drugs that recognise, target and stick to specific proteins on the surface of cancer. They can stimulate the body’s immune system to destroy these cells. Another way to use the immune system is to modify immune system cells, called T-cells, to allow them to attack ALL cells more efficiently.
Stem cell transplant
A stem cell transplant involves the use of intensive treatment to kill as many leukaemia cells as possible. The patient is then given a transplant of healthy blood-forming (stem) cells. In ALL, the stem cells used are usually healthy stem cells from a sibling (brother or sister) or from an unrelated matched donor. This is called a donor (or allogeneic) transplant. Sometimes a patient may be given a transplant using their own healthy stem cells, collected after initial treatment. This is called an auto (or autologous) transplant – this type of transplant is not often used for ALL patients.
Pre-transplant treatment, called conditioning, may include high-dose chemotherapy plus whole body irradiation, to completely kill off the bone marrow. This is called myeloablative conditioning and is only suitable for younger, fitter patients, because of the high doses of chemotherapy. For older, and/or less fit patients, conditioning uses lower doses of chemotherapy without radiation. This is known as reduced-intensity conditioning and is more easily tolerated by older or less fit patients.
In ALL, a stem cell transplant is most often given as a form of consolidation, following induction therapy. It is usually considered for patients with high risk disease or for patients whose disease is difficult to control (refractory disease) or those who have a relapse.
The side effects of a stem cell transplant depend on the type of pre-transplant treatment and the source of stem cells. If you are being offered this type of treatment, you will be given detailed information and a chance to ask questions.
In adult ALL, it is possible for leukaemia cells to get into the fluid around the brain and spine (cerebrospinal fluid or CSF). This is called central nervous system (CNS) disease and may be present at diagnosis or may develop later. Because drugs given in the normal way cannot get into the CSF, it is necessary to give additional treatment to deal with this. This may be done at diagnosis, if there are signs of CNS involvement, or it may be given later in during induction treatment.
To prevent CNS relapse, you will have injections of drugs into the CSF by lumbar puncture during induction treatment. This is called intrathecal injection, or intrathecal therapy. You will be given detailed advice about lumbar puncture and about intrathecal injections, including possible side effects and how to avoid these. If you are not going to receive whole body radiation as part of a stem cell transplant, you may also have radiation to the head and spine to clear any remaining leukaemia cells.
Stages of treatment of adult ALL
Remission induction, often just called induction, is the use of chemotherapy to induce remission, ideally complete remission (CR) which means that no leukaemia cells can be found in the blood or bone marrow, using standard tests. It is important to understand that remission, even CR, does not mean cure; if treatment stops at this point, almost all patients will relapse – their ALL will return. Induction is the same for most patients, apart from any trial variations. Patients who are Philadelphia chromosome positive or have CNS disease at diagnosis will have additional treatment to deal with this.
Remission induction for ALL uses combinations of chemotherapy drugs plus steroids. You will be given details of the drugs which you are going to receive during your treatment.
At the end of remission induction, special tests are carried out to look for minimal residual disease (MRD), which is the presence of very small numbers of leukaemia cells. MRD test results are very important in classifying patients as high risk (MRD positive, whether or not they have other risk factors) or standard risk (MRD negative and no other risk factors).
This is a period of treatment based on use of high-dose methotrexate along with other drugs. As with induction, you will be given details of any drugs being used and what side-effects you may experience. Intensification is intended to kill off any leukaemia cells which have survived induction treatment.
Consolidation treatment is given after remission induction to reduce the risk of a relapse. Several factors affect the choice of consolidation treatment, including age and risk status.
For patients who do not have a stem cell transplant consolidation therapy will use similar combinations of drugs to those used for remission induction, but these are given in lower doses. You will be given detailed information about your planned consolidation therapy before this starts.
Maintenance therapy is low-dose chemotherapy and steroid treatment, given as an outpatient. Without maintenance therapy, there is a higher chance that the ALL will come back – a relapse. When this happens, it is often less responsive to treatment. Maintenance lasts for many months, with the total time from start of treatment being between two and three years.
Treatment of refractory/relapsed adult ALL
With modern treatment options, it is very uncommon to have no response at all to treatment, which is known as refractory ALL. When there is a good initial response but ALL returns this is known as relapse and again is less common with current treatments.
If you have refractory or relapsed ALL, your specialist will discuss your treatment options in detail. There are several new treatment approaches being studied – see below under the heading “New treatments and treatments on the horizon”. Often, newer treatments are initially introduced in clinical trials for treatment of refractory or relapsed ALL.
ALL treatment in older adults
In patients over the age of about 60 years, standard treatment may be too toxic. In this age-group, treatment is chosen on an individual basis, depending on the patient’s general health and any other health problems. If this applies to you, your consultant will discuss treatment options and you will have a chance to ask questions before any decisions are made.
Supportive care includes treatment to prevent infections and to manage them when they happen and treatment to deal with the side-effects of adult ALL treatment. Improvements in supportive care have played a crucial part in improving the survival of patients with adult ALL.
Because both adult ALL and its treatment affect the bodies ability to produce healthy blood cells, most patients with adult ALL need transfusions of red blood cells and often of platelets. It is not possible to transfuse white blood cells but it is now possible to have injections of growth factors, which help the body to produce more white cells. This will reduce the frequency and severity of infections.
Much of supportive care is based on good nursing care, but protecting yourself from infection outside the hospital is very important. You will be given information on this and will be shown how to recognise infection, or other complications, and who to contact and what to do.
During treatment, you may come into contact with a palliative care team who can help to control some of the symptoms you may be experiencing.
The palliative care team can provide additional advice and support when symptoms are not easily controlled. Their input can be temporary or for a longer period of time as some medical treatments can be fairly aggressive and call for equally aggressive palliative approaches to your care. Care provided by your palliative care team can help you tolerate the side effects of these treatments
Not all treatments, sadly, are successful and sometimes patients have to be told that the disease is too progressive for any treatment to control it. That conversation will most likely be started by your medical team and most hospitals will have palliative care teams that have experience in dealing with end of life and related symptom control.
Unfortunately, treatments do come with some side effects but you may not experience all of them. It’s difficult to predict exactly what side effects you’ll experience as different people react to treatment in different ways. Your medical team will be able to answer any questions you might have on any side effects you may experience
Short term side effects
Short term side effects can last for a few days or weeks, but for some, can last for the duration of treatment. Short term side effects include:
- Fatigue – a common side effect of chemotherapy treatment. Fatigue isn’t simply tiredness which passes with rest; you may feel generally tired all the time or you may tire very easily after doing normal, everyday tasks.
- Nausea and sickness – this can be well-managed with antisickness drugs (antiemetics).
- Infection – all patients with ALL will at some point get an infection which requires treatment with antibiotics.
- Bleeding – chemotherapy can make you more prone to bleeding especially from the nose or gums.
- Diarrhoea – this can usually be well-managed with medication.
- Sore mouth – chemotherapy can cause inflammation of the tissue inside the mouth.
- Loss of taste and appetite – your taste and appetite can be affected during treatment so it’s important you drink plenty of fluids to stay hydrated. There are food supplements which can be taken to help maintain your energy levels.
- Organ dysfunction – chemotherapy can affect the functioning of your liver, kidneys or lungs.
- Hair loss – you may want to wear a wig or some form of headwear if you’re affected by hair loss. Your healthcare team will be able to chat to you about your options.
- Bone pain with steroids
- Thrombosis and pancreatitis with asparaginase
- Headaches with lumbar punctures
Long term side effects
The fatigue will improve when treatment ends, but it may take months before you feel back to normal. After a transplant, it may take a year or longer for patients to feel recovered. Although fatigue cannot be completely prevented, there are ways of managing fatigue. Perhaps unexpectedly, resting a lot often makes fatigue worse, while remaining as active as you can manage often makes it easier to cope. If you are feeling very tired, you should tell your healthcare team as they can offer help.
Loss of fertility
Some of the drugs used to treat ALL can cause temporary or permanent infertility. Your doctor will talk to you about this in more detail before you start your treatment. The effect of treatment on fertility is a common concern that many patients have, and one that also impacts on their partners and families too. However, as treatment for ALL usually needs to start as quickly as possible, there’s not always enough time to store sperm or embryos. If you’re having treatment for ALL at an age when you’re thinking about having children, now or in the future, you should discuss the options for protecting your fertility with your doctor. Your doctor knows the details of the treatment you’re having, and is the best person to answer your questions. You can write down any questions you have so that you are clear about your treatment, and the effect it’s likely to have on you, before it starts. Some drugs have less effect on your fertility than others, and it is possible for couples to go on to have healthy babies after one partner has been treated for ALL. Unfortunately, people who’ve had a stem cell transplant after high doses of chemotherapy or whole body irradiation are very likely to be permanently infertile. It’s natural to worry about the effects of treatment on any children you might have after your treatment. However, evidence from clinical studies has shown that any cancer treatment a parent has doesn’t lead to an increased risk of cancer or other health problems in their children.
Some of the drugs (anthracyclines) used to treat ALL may affect the heart. This is rare because healthcare teams are careful to limit the doses you have. Your heart function will be carefully monitored during and after treatment, and the drugs you’re given may be altered if any heart problems occur.
Once your treatment is finished, you’ll need to have regular check-ups at the hospital. These may be frequent at first, probably one to two months, then every few months until they become yearly at five years or earlier. The exact frequency and timing will depend on the treatment you have received. The purpose of follow-up is to monitor you and look for signs of relapse or complications.
If you notice any new symptoms or something is worrying you, you should contact your medical team as soon as possible.
After treatment, you may still have some physical effects to cope with. It’s important to remember that it can take some time for you to fully recover, so try not to expect too much of yourself too soon. How quickly things improve will depend on the treatment you’ve had, your age and general health.
New treatments and treatments on the horizon
There are several new types of drugs being studied for the treatment of ALL. These classes are all more specific in their effects than standard chemotherapy. This is because they attack features of the leukaemia cells, while having much less effect on normal cells than chemotherapy.
Most of these fall into two groups:
- Immune system based treatments
- Monoclonal antibody targeted at specific markers on ALL cells
- Monoclonal antibody linked to drug (drugs too toxic to use conventionally)
- Modified antibodies (which activate immune system cells to attack ALL cells)
- Bispecific T-cell antibodies (BITE) Blinatumomab
- Modified patient immune cells
- Chimeric antigen receptor (CAR) T cells (immune cells with Improved ability to attack ALL cells)
- Tyrosine kinase inhibitor (TKI) drugs (for Philadelphia positive ALL) – Tyrosine kinases are either abnormal proteins produced by leukaemia cells, or normal proteins produced in large amounts by leukaemia cells
- Other TKIs – several are being tested in clinical trials
The aim of these newer, more targeted therapies is to reduce the amount of chemotherapy needed, which will reduce side-effects. Some experts have suggested that it may eventually be possible to treat some patients without any chemotherapy.
A drug called nelarabine is showing promise in the treatment of T-cell ALL.
At present, these newer drugs (except TKIs) are either only available for ALL patients in clinical trials, or are not available on the NHS in the UK.
Questions to ask your doctor
We understand going through a blood cancer through journey can be difficult. It may help to talk to a close friend or relative about how you are feeling. Here are some questions that may be useful to ask your doctor.
- How would I know if I had ALL?
- What tests will I need to have?
- What will the tests show?
- How long will the results take?
- How rare is ALL?
- What sort of treatment will I need?
- How long will my treatment last?
- What will the side effects be?
- Is there anything I should or shouldn’t eat?
- Will I be able to go back to work?
- Where can I get help with claiming benefits and grants?
- Where can I get help dealing with my feelings?
We have free patient information available for ALL patients.
You can download the booklets on our information pages here.
Alternatively, you can have the information delivered free of charge by requesting it through our resources page.
Support for ALL patients
There is also a general leukaemia support group on Facebook which is ran by Leukaemia Care. To request to join, click here.
Offline support groups
There area number of haematology support groups in the UK. Find out more on our support groups page.
Acute Leukemia Advocates Network (ALAN)
ALAN is an independent global network of patient organisations, dedicated to changing outcomes of patients with acute leukemias. It aims to build capacity in the members of the network to deliver tailored services to acute leukemia patients and carers on the national level, while joining forces between organisations on the policy and research level across countries.
Other ALL charities
BPositive aim is to provide support, information and access as well as promoting the cause and case of patients with acute leukaemia and their families. Find out more on their website at bpositive.org.uk
Published date: November 2016
Review date: December 2018