Acute Lymphoblastic Leukaemia

About acute lymphoblastic leukaemia (ALL)

Leukaemia is a cancer of the white blood cells. White blood cells help to fight infection.

There are two different types of white blood cell – lymphoid cells (also known as lymphocytes) and myeloid cells. Normally these cells, which are produced in the bone marrow, repair and reproduce themselves in an orderly and controlled way. In leukaemia, however, the process gets out of control and the cells continue to divide but do not mature.

Acute lymphoblastic leukaemia is an overproduction of immature lymphoid cells, called lymphoblasts or blast cells.

Immature lymphoid cells fill up the bone marrow and stop it making healthy blood cells. As these cells are immature, they cannot work properly. This puts the child at increased risk of infection. Symptoms of leukaemia in children such as bruising and anaemia are caused by the bone marrow’s inability to make enough healthy red blood cells and platelets.

There are several types of childhood acute lymphoblastic leukaemia. These are identified according to the type of lymphoid cell affected and the stage during its development at which it becomes leukaemic:

• The affected lymphocytes may be either precursor (>98%) or mature
• Precursor cell leukaemias may involve either of the two types of lymphocyte: B-cells (87%) or T-cells (13%)
• Precursor B-cell ALL is further divided into three categories: null-cell, common ALL and pre-B ALL
• Common ALL is the most common type of childhood ALL, accounting for up to 70% of cases.

Knowing the type of ALL is important as it helps doctors work out the best treatment.

Incidence

ALL accounts for almost 80% of all childhood leukaemias and around 25% of all childhood cancers with around 400 new cases diagnosed every year in the UK.

There is a peak in incidence of acute lymphoblastic leukaemia in children aged two to three years; more than half of all children diagnosed with acute lymphoblastic leukaemia are under the age of five years.

Boys have a greater risk than girls of developing ALL, by a factor of 4:3. The reason for this difference between the sexes is not known. Boys also require a longer duration of treatment (see below).

Survival

Until the 1960s, childhood leukaemia was incurable. Today, thanks to improvements in care and sustained investment in research, the outlook for young patients diagnosed with ALL is good, with a survival rate of over 90%.

Of the different types of ALL, children with so-called common ALL have the best prognosis.

Acute lymphoblastic leukaemia survival rate is highest in children diagnosed between one and four years of age.

Childhood leukaemia develops quickly. The symptoms are quite general, including:

• frequent, persistent infections
• unusual bleeding and bruising
• tiredness
• paleness
• breathlessness

It’s possible for some or all of these symptoms of leukaemia in children to be apparent.

A diagnosis of childhood leukaemia can be made on the basis of a blood test, which will reveal low numbers of normal white blood cells and large numbers of abnormal white blood cells.

At this point, the child will be referred to hospital for further tests. A sample of bone marrow will be taken to confirm the exact diagnosis.

Whilst around 90% of children with acute lymphoblastic leukaemia can now be successfully treated, treatment is long and gruelling, lasting two years for girls and three years for boys.

The principal treatment is chemotherapy. A combination of chemotherapy drugs and steroid medicines is given in several stages, or blocks, as outlined below.

As well as chemotherapy, some children will also require radiotherapy and/or a stem cell (bone marrow) transplant.

1. Remission induction. The initial aim of treatment is to achieve a state called remission where most of the leukaemic cells have been killed, allowing production of normal blood cells to resume. This stage involves the use of several drugs in combination and usually lasts between three and eight weeks, depending how quickly the child responds to treatment.
2. Consolidation (also known as intensification). Almost all children will have leukaemic cells remaining when they achieve remission. This is known as minimal residual disease or MRD. It is necessary to give further blocks of treatment to eradicate the disease completely and achieve a cure. Standard consolidation therapy involves two blocks of chemotherapy at intervals of roughly four and eight months from diagnosis but protocols vary according to a number of factors including MRD status. For high-risk children, treatment may be intensified by the inclusion of additional blocks of treatment, or by the inclusion of additional drugs in the periods of maintenance therapy between the intensification blocks. Intervals of time are left between blocks of treatment in order to allow the child’s body to recover and to minimise the risk of treatment-related complications.
3. Central nervous system (CNS) directed therapy. Some leukaemic cells may cross the barrier into the fluid which surrounds the brain and spinal cord. The chemotherapy drugs do not penetrate this barrier very well, so it is necessary to inject the drugs directly into the fluid. This is known as an intrathecal injection. Occasionally radiotherapy may also be used to target the CNS.
4. Maintenance therapy. Children with ALL require a phase of extended ‘maintenance’ therapy to prevent relapse. This involves taking daily tablets and having monthly injections of chemotherapy drugs. Maintenance therapy takes the total duration of treatment to two years for girls and three years for boys. This stage of treatment is carried out on an outpatient basis, usually on a ‘shared care’ basis between the specialist centre and the child’s local hospital. Children will usually be well enough to resume most of their normal activities and return to school. They will be closely monitored during this stage.
5. Stem cell (bone marrow). Transplantation is not routinely used in the treatment of children with ALL. It is only used in certain high-risk groups – in children who have relapsed early in their treatment or who have experienced more than one relapse.
6. Radiotherapy. Is not routinely used in the treatment of childhood acute lymphoblastic leukaemia. Children who are found to have leukaemic cells in their brain and spinal fluid when they are diagnosed may need radiotherapy. In some situations, it may be necessary for boys to have radiotherapy to their testicles since leukaemic cells can survive in the testicles despite chemotherapy.

Following completion of treatment, all children will continue to be monitored for symptoms of both disease relapse and treatment complications. Checks will take place every two or three months for the first year, gradually becoming less frequent.

Commonly used terms in treatment Stem cell transplantation
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The treatments used in ALL often cause side effects.

Most side effects are temporary and can be minimised with good supportive care. The most common effects include nausea and vomiting, hair loss, reduced resistance to infection, bruising and bleeding, tiredness and diarrhoea.

Treatments can also cause long-term or ‘late’ effects. These are relatively rare and most children who survive ALL will grow and develop normally.

The main risk of late effects is in children who receive radiotherapy to prevent central nervous system (CNS) relapse. Radiation to the brain is associated with a number of problems including impairment of growth and reduced educational achievement. To minimise the risk, only a minority of children receive cranial irradiation routinely, and those that do receive the absolute minimum dose of radiotherapy.

Other documented problems associated with either chemotherapy or radiotherapy include cardiac problems, fertility problems and a small elevated risk of second cancers.

Follow-up and relapse

All children will be followed-up at regular intervals after their treatment for ALL to monitor their progress and check for treatment-related problems.

Although most children with ALL will achieve remission, up to a quarter of these children will relapse – their disease will return. Most relapses occur within three years of treatment ending.

Relapsed ALL tends to be more resistant to treatment but many children can be successfully re-treated.

A stem cell transplant may be an option for some children who relapse early in treatment or who experience more than one relapse.

The likelihood of a relapse progressively decreases with time, particularly once maintenance treatment is completed.

Most children have their treatment as part of a clinical trial. These aim to improve understanding of the best way to treat the childhood leukaemia, usually by comparing the standard treatment with a new or modified version. The dramatic improvement in survival from ALL has been brought about by a continuous series of clinical trials which have pioneered new ways of treating the disease.

Participation in trials is optional but may offer the opportunity to receive new treatments.

Children with Cancer UK is funding a number of research projects aimed at improving our understanding of childhood leukaemia and improving the outlook for young patients.

Read about Ace’s victory against acute lymphoblastic leukaemia, as told by his dad, Ian.

28 January 2008. A day that changed my whole family’s life. My son Ace was three years and three months old when he was diagnosed with acute lymphoblastic leukaemia.

One day, Ace was being a real little terror and I poked him gently in the chest and told him to behave. That night, he had a large bruise on his chest.  The next day, the bruise still there, but bigger and more purple. Two days later, he turned white as a ghost – he was just so pale, it was horrible.

We went to see our family GP, and when she heard the story and saw the bruise, she requested a blood test. After the blood test at hospital, my wife dropped me at work on the way home. Within an hour, she called me saying: ‘We have got to get Ace back to hospital now. He is in a serious condition.’

The next day, the doctors wanted to do a bone marrow aspiration, so we signed the forms and gave our permission. When they told us the risks, we were all still in a daze. We never had to deal with this before so we just accepted everything. Two days later, we were called into our consultant’s office and she broke the news: ‘Ace has acute lymphoblastic leukaemia’.

I was so angry. Getting leukaemia at any age is not right. Ace needed a Hickman line, chemotherapy and steroids for over three and a half years. After a while, all of Ace’s hair came out – eyebrows, head, the lot. I still have some of his original hair in my wallet. I was never ever embarrassed to walk down the street with him, he is my little warrior.

Throughout Ace’s treatment, we had some great times at the hospital. It does not matter how much poison they pump into the kids, they all still smile the biggest smiles. We were extremely humbled by the amount of support we received, not only from the hospital, doctors, nurses and play specialist but charities sending us away for a few days here and there.

Thanks to supporters of Children with Cancer UK, we went on a holiday to Italy at the end of Ace’s treatment. It was amazing, our first proper holiday in years and great for all the kids and us parents. Ace is doing very well. He started secondary school in 2017 and is achieving some great results.

If you’ve been touched by Ace’s journey, help us invest in the high quality research that really matters which would otherwise go unfunded. This helps to support children with cancer so they can be with their families for longer.

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