Video: Professor Anthony Moorman describes what Acute Lymphoblastic Leukaemia is.
Acute lymphoblastic leukaemia (ALL) is an aggressive type of leukaemia in which immature lymphocytes called lymphoblasts or leukaemia cells start multiplying uncontrollably, resulting in increased numbers in the blood and bone marrow. Lymphocytes are a type of white blood cell involved in the immune response. ALL is characterised by too many leukaemia cells in the bone marrow and the blood. It can spread to the lymph nodes, spleen, liver, central nervous system and other organs.
When you have ALL, the excessive number of lymphoblasts or leukaemia cells begin to accumulate in the bone marrow, preventing it from producing healthy blood cells.
What causes Acute Lymphoblastic Leukaemia?
- In the majority of cases, the cause of ALL is generally unknown. However, there are certain characteristics that are linked with a higher chance of developing ALL:
- Age – Increasing age, older than 70 years.
- Gender – Men are slightly more likely than women to develop adult ALL.
- Genetic factors – Under 5% of cases of ALL are related to genetic syndromes such as Down’s syndrome, Fanconi anaemia, Klinefelter syndrome and ataxia-telangiectasia. Family members with these conditions cannot pass ALL on to their children.
- Virus association – A connection has been shown between B-cell ALL and the Epstein- Barr virus which causes glandular fever, and also between T-cell ALL and T-lymphotropic virus type 1 which generally causes no signs or symptoms.
- Previous cancer treatment – Being treated with chemotherapy or radiotherapy may lead to development of acute leukaemia. This is uncommon and is called therapy related leukaemia. These patients are more likely to develop AML rather than ALL.
- Environment – Some chemicals and high levels of radiation may increase the chance of developing leukaemia. However, strict rules to limit occupational exposure means that these factors play a very small part in causing ALL in the United Kingdom.
Signs and Symptoms
Common initial symptoms of ALL are relatively nonspecific and may be difficult to recognise. On occasion, it can be picked up from a routine blood test. However, without treatment, ALL usually progresses quickly so the majority of patients with ALL will have symptoms when they are diagnosed.
As mentioned previously, patients with ALL produce too many leukaemia cells which overcome the bone marrow, and prevent it producing adequate levels of red blood cells, platelets and white blood cells. Reduced levels of these cells leads to a decrease in distribution of oxygen to the body tissues, an increased risk of bleeding, and prevention of the body fighting infection, respectively.
The most common signs and symptoms of ALL are a result of these changes. They are:
- Weakness or fatigue
- Skin pallor
- Fever and/or night sweats
- Unexpected weight loss or anorexia
- Easy bruising, including bleeding gums, purplish patches in the skin (purpura), or flat, pinpoint spots under the skin (petechiae)
- Frequent chest or urinary tract infections
- Unexplained usually painless swollen lymph nodes in the neck, armpit, or groin
- Swelling or discomfort in the abdomen due to enlarged spleen and/or liver
- Difficulty breathing
- Pain in the bones or joints
Tests for diagnosing ALL
The tests that you may have include:
- Full blood count: This is a routine blood test which measures the number of red cells, different types of white cells, and platelets in the blood. The blood is smeared onto a microscope slide, allowing the blood cells to be examined under the microscope.
- Bone marrow biopsy: The bone marrow sample can be taken from the hip bone under local anaesthetic, using special biopsy needles: liquid bone marrow (aspirate) and/or a tiny core of bone marrow tissue (trephine).
- Lumbar puncture: Lumbar puncture with analysis of the cerebrospinal fluid is used to evaluate if the central nervous system (CNS; brain and central cord) is involved. If the CNS is involved, a magnetic resonance imaging (MRI) of the brain should be performed.
- Chromosome abnormalities or gene mutations tests: Blood or bone marrow may be tested to check for chromosome abnormalities or gene mutations of the leukaemia cells.
- Immunophenotyping: A process that analyses the types of antigens or markers on the surface of the leukaemia cells. According to which antigens are present, it is possible to identify the type of leukaemia.
- Minimal residual testing (MRD) testing: This is a sensitive test using patient-specific markers identified at diagnosis. These individual patient markers are then tracked or measured at certain timepoints during treatment to help determine response to therapy. MRD can be measured using a number of different techniques including PCR (polymerase chain reaction) based techniques or flow cytometry. MRD testing tells your doctor how ‘deep’ your remission is, and is important in planning the next phase of your treatment.
- Other tests: X-rays, ultrasounds or scans including computer tomography (CT) and MRI are done to assess the impact of the leukaemia on the organs of the body.
Blood tests, bone marrow samples and scans will be repeated throughout treatment to monitor your response to treatment.
Classification and risk grouping of ALL
ALL can be classified into different specific groups using the various diagnostic tests, and this has implications for the patient’s treatment selection and an indication of their prognosis. ALL can be classified into groups according to their characteristics:
- B-cell or T-cell leukaemia
- Philadelphia chromosome-positive (Ph+) or chromosome-negative (Ph-)
- Genetic attributes: Specific chromosome or mutations
The most important part of classifying ALL is risk grouping, which can suggest the prognosis that patients with ALL will have using standard treatments. There are two risk groups in adult patients with ALL:
- Standard risk: Patients who do not have any risk factors.
- High risk: Patients with risk factors based on age, white blood cell count, genetic characteristics and response to initial treatment.
By adjusting treatment according to risk groups, the results for patients can be improved. You should ask your specialist about risk groups and what they mean for your treatment.
Because ALL progresses rapidly, nearly all patients start treatment soon after diagnosis, even within a number of days. You can refuse treatment at any time, but it is important that you understand clearly what will happen if you do. You can ask for a second opinion at any time. As far as possible, all decisions about treatment will take your wishes into account.
Overview of treatment
Treatment of ALL is normally divided into three phases known as induction, consolidation (sometimes called intensification) and maintenance. The length of treatment typically lasts between two and three years.
This is the first treatment given after diagnosis and is intended to kill the majority of the leukaemia cells and induce complete remission. Induction treatment uses combinations of drugs and is normally given in hospital initially, but may in part be given as an outpatient depending on the practice at your centre. Achieving complete remission does not mean cure. Without consolidation, nearly all patients will relapse (the ALL will return). Disease status will be reassessed by a repeat bone marrow biopsy after the first stage of induction chemotherapy. MRD will be assessed usually after the second stage of induction chemotherapy, but may also be assessed after the first stage of induction treatment.
- Complete remission occurs when the blood cell counts have returned to normal limits, and less than 5% of leukaemia cells are still present in the bone marrow.
- Complete molecular remission means there is no detectable evidence of leukaemia cells anywhere in the body by MRD methods; i.e. MRD is said to be negative. MRD is a measure of the presence of leukaemia at a molecular level rather than at a cell level.
Consolidation treatment is given following achieving complete remission and is intended to consolidate or reinforce remission, and reduce the risk of a relapse. Consolidation therapy uses similar combinations of drugs to those used for induction of your remission, but at lower doses. You will be given detailed information about your planned consolidation therapy before it starts.
CNS intensification treatment
This is a specific chemotherapy treatment that has enhanced capability to treat any leukaemia cells that may be present (detectable or undetectable) in the central nervous system, (made up of the brain and spinal cord). It is aimed at giving additional protection to this site to reduce the chances of a patient having a CNS relapse in the future.
Maintenance treatment is given to prevent a relapse, which is when your ALL returns after complete remission has been consolidated. Maintenance treatment is usually low dose chemotherapy with a steroid drug, and is given as an outpatient. Without maintenance therapy, there is a high chance that the ALL will return. Maintenance treatment is often given for two to three years because patients are often less responsive to treatment when they have relapsed.
Potential treatment options
The mainstay of the treatment for ALL is chemotherapy. For the treatment of ALL,
chemotherapy drugs are usually given in combination. The most common drugs used to treat adult ALL are:
- Asparaginase or pegaspargase
Steroids are often added to help improve the effectiveness of the chemotherapy. You may be given a targeted therapy drug such as an immunotherapeutic monoclonal antibody which is a drug developed to target specific components of the leukaemia cells. This feature means they tend to cause less side effects than chemotherapy which has a broad approach to killing all lymphoblast cells, often including normal cells as well. Some patients may also have an allogeneic stem cell transplant (allo-SCT), which is a stem cell transplant from a matching healthy donor to consolidate their remission.
The treatment option that your haematologist will select for you will take into account the following factors:
- Fitness level, and specifically whether you can withstand intensive chemotherapy.
- Age: which can affect how well your body responds to treatment. Elderly patients can usually receive relatively intense treatment as long as they are fit.
- Disease characteristics: B-cell or T-cell-ALL; Philadelphia-positive or -negative type ALL; central nervous system disease at diagnosis. For example, patients who are Philadelphia-positive or have CNS disease at diagnosis will automatically have additional treatment with their induction treatment.
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 medical team about ALL
We understand going through a blood cancer 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: December 2020
Review date: December 2023