What is the goal of chemotherapy administration for pediatric patients with blood related cancers?

Research has shown that we need to give different treatment to babies that are under 1 year old when they are diagnosed. This information is for children over 1. Your hospital consultant can give you information about the treatment plan if your child is under 1.

Doctors plan your child’s treatment in one of the major children’s cancer centres. This is called the principal treatment centre (PTC). Your child has some of their treatment in this specialist centre, but some care takes place at a hospital closer to home. This hospital is called your:

• shared care hospital
• paediatric oncology shared care unit (POSCU)

Blood tests, dressing changes or other aspects of care might take place in your home.

After diagnosis children start treatment for ALL quickly. This is because ALL can cause serious problems quickly if it’s not treated as soon as possible.

Children's cancer centres have teams of specialists who know about childhood ALL and the best way to treat it. More than 90 out of 100 children (more than 90%) now survive childhood ALL.

The main treatment for ALL is chemotherapy.

Clinical trials

Most children having treatment for ALL have it as part of a clinical trial when one is available.

Chemotherapy usually works well for children and young adults with ALL. But we know from research that it is important to look at the risk of the leukaemia coming back after treatment (relapse) and plan treatment based on this risk. This means giving less treatment to people with a low risk of their leukaemia coming back. And giving more treatment to people with a higher risk of the leukaemia coming back.

To do this, a new international trial for children, teenagers and young adults is now open at some centres in the UK. It will be opening at more soon. The study is called AllTogether1.

Your child does not have to take part in the trial. They will still get standard treatment

AllTogether1 will run for up to 6 years, so until about 2026.

The information on this page will be based on your child having treatment with the ALLTogther1 trial. It is a very complicated study and we are unable to go into detail here. The overview might help you feel more informed. Talk to your child’s treating team about what treatment is first and what happens next.

How long does treatment last?

Treatment lasts around 2 years after your child has finished the induction part of the trial. Induction lasts about 4 weeks.

For a small number of children the length of treatment will be different for those who have leukaemia that is at a very high risk of coming back after treatment. These children may need to have different treatments such as a stem cell transplant

Your child will have most of their treatment as an outpatient. For their first treatment (induction) they will stay in hospital until they have recovered and it’s safe for them to go home. This might be after a couple of weeks. It’s hard to be precise but your child is likely to be in and out of hospital depending on how they cope with the treatment.

Your child will be an inpatient at certain points later on in their treatment if they are having:

• a stem cell transplant
• CAR-T cell therapy
• blinatumomab a type of targeted drug for children with Down syndrome
• high dose methotrexate (a particular phase of chemotherapy)

Decisions about treatment

The specialist team make a treatment plan depending on a number of factors. These help your child’s doctors to decide on the best treatment group for your child based on the risk of their leukaemia coming back after treatment.

Some of these factors include:

• your child’s age (if they are under 12 months old or over 10 years old)
• the level of white blood cells in the blood when your child is diagnosed (doctors call this the white cell count)
• the type of cell the leukaemia started in
• if there are leukaemia cells in the fluid around the brain or spinal cord (cerebrospinal fluid)
• any genetic changes in the leukaemia cells themselves - rather than those inherited from parents
• if your child has a condition that makes them more susceptible to ALL such as Li-Fraumeni syndrome. However, Down syndrome is an exception to the rule with this current trial.
• if they have had cancer before

Doctors look for changes to chromosomes within the leukaemia cells themselves. One change leads to a type of leukaemia called Philadelphia positive (Ph +ve ALL). Around 3 to 5 out of every 100 children (3 to 5%) who get ALL have the Philadelphia chromosome change.

Children with Philadelphia positive ALL have slightly different treatment than we talk about here. They usually have a targeted cancer drug called Imatinib from day 15 of the start of their treatment. Your child’s doctor will go through in detail the treatment plan with you.

Below is a short video to explain what Philadelphia positive leukaemia is.

Transcript

The human body is made up of trillions of cells. Inside each cell is a nucleus and within the nucleus are the cell’s chromosomes. There are 23 pairs in total. 

Chromosomes are made up of DNA, which gives the instructions that tell a cell what to do. Sections of DNA are called genes. They carry the information that makes you you. For example, they tell your body what colour your hair will be or what colour your eyes will be.

Genes also tell your cells when to divide and grow, and when to die.

When cells divide to make new cells, they make exact copies of the chromosomes.

In Philadelphia chromosome positive leukaemia an abnormal change happens to chromosomes 9 and 22. Part of chromosome 9 breaks off where the gene ABL1 is located and part of chromosome 22 breaks off where the BCR gene is located. The broken parts swap places creating a new gene on chromosome 22.

This new chromosome is called the Philadelphia chromosome and the new gene is called BCR-ABL1. This new gene tells the cell to make a large quantity of a protein called tyrosine kinase which encourages leukaemia cells to grow.

There are targeted cancer drugs that can block the protein and stop the leukaemia from growing. These drugs are called tyrosine kinase blockers. You take them as tablets.

For more information about your type of leukaemia and treatments go to CRUK.org/about-cancer/leukaemia.

Measuring if treatment is working

Your child’s doctors will check how well treatment is working. They do this on day 15 after starting treatment. It is then continued at different points through treatment. One way of measuring this is by looking for measurable residual disease (MRD).

Measurable residual disease (MRD)

Measurable residual disease is a sensitive test. It can see if there are leukaemia cells still in the bone marrow, even if it looks like the ALL has gone away (remission) using other tests.

Doctors expect to see some MRD early on in treatment. It doesn’t mean your child’s leukaemia won’t go away with further treatment. It looks at how well your child is responding to the treatment they are getting.

Depending on the results of the MRD test, and other tests, your child might have changes to their treatment. This is to make sure they are getting the best treatment they need.

Don't be afraid to ask your doctor or specialist nurse any questions you have about the treatment. You might want to encourage your child to ask questions too if they are able. Write down a list of questions you want to ask and to take a close friend or relative with you when you go to see the doctor.

Treatment phases

ALL treatment is in blocks (phases). Not all children have the same phases and these can differ depending on the risk group your child is in. It depends on your child’s risk group as to:

• how much chemotherapy your child has
• how strong the chemotherapy treatment is

Your child is monitored carefully to check that they are managing any side effects of treatment before the next phase of chemotherapy.

Below is an overview of the different phases of treatment for AllTogether1 trial. You can find more detailed information about each phase further down the page.

The trial researchers are making other changes to treatment in the study. This will affect fewer children. The aim of these changes are to try and improve treatment by adding newer drugs, or newer ways of treating leukaemia to standard treatment.

Your child’s team will talk to you in detail if they think this part of the trial is suitable for them. Some of the changes Include:

Nelarabine

Your child might have nelarabine if they have high risk T-cell ALL. Nelarabine is a chemotherapy drug.

Blinatumomab for people with Down syndrome

Your child might have a drug called blinatumomab if you have Down syndrome and are in the intermediate risk or high risk group. Blinatumomab is a type of targeted cancer drug called a monoclonal antibody (MAB). It works by targeting a certain protein on the leukaemia cells so your immune system can recognise them. The immune system can then attack and kill the leukaemia cells.

Inotuzumab ozogamicin

Researchers are looking at adding this drug before maintenance treatment, as some children might benefit from more treatment. Inotuzumab ozogamicin is also type of monoclonal antibody with a substance attached. It finds the leukaemia cells by targeting a certain protein on them. This protein is called CD22. It then delivers the substance directly into the leukaemia cells and kills them.

CAR-T therapy

Some people with high risk ALL might need a lot of chemotherapy and sometimes a stem cell transplant to get their leukaemia under control.

This trial would like to find new ways of treating high risk ALL, which are safe and work well. One potential new treatment is CAR-T cell therapy.

The study researchers are interested in finding people with high risk ALL who are able to join a different CAR-T study.

Your doctor will talk to you about different treatment options if CAR-T therapy is not available to you.

Induction treatment

The aim of the induction phase is to try and get rid of as many leukaemia cells as possible. It's also called remission induction. In remission means that there is no sign of the leukaemia in your child’s blood or bone marrow when looked at with a microscope.

There are 5 induction groups, labelled A to E. Your child will start the induction treatment based on their risk factors.

The main treatments are:

• chemotherapy
• steroids
• targeted cancer drug (imatinib) for patients with certain genetic changes

Around 98 out of 100 children (around 98%) go into remission after 4 to 6 weeks of induction chemotherapy.

Children usually stay in hospital on the children’s cancer ward for the first couple of weeks while they start induction treatment. One carer can usually stay with them while they have this treatment.

Staying in hospital means their team can keep an eye on them for any problems or side effects of treatment. It also allows you to ask lots of questions and become more familiar with the team and treatment plan.

Your child has an MRD test at two points during the induction phase to check the response of the leukaemia to the treatment.

Consolidation 1

The aim of consolidation 1 treatment is to:

• lower the amount of any residual leukaemia – these are the cells that the doctors looked for using the MRD test
• prevent any leukaemia cells from spreading to the brain or spinal cord

The main treatment is chemotherapy. Consolidation 1 treatment takes about 6 weeks. Most children have consolidation treatment as an outpatient or on the daycare ward.

Consolidation 2 and 3

Consolidation 2 and 3 treatment aims to get rid of any remaining leukaemia cells. The main treatment for consolidations 2 and 3 is chemotherapy. It contains high amounts (doses) of a chemotherapy drug called methotrexate. This means your child stays in hospital for a few days for this part of the treatment.

Consolidation 2 and 3 treatment lasts about 7 weeks. 

Depending on your child's risk group they might not have consolidation 3.

Delayed Intensification

Intensification treatment aims to use strong chemotherapy drugs when there are very few leukaemia cells left in the blood or bone marrow. This is to try and further reduce the amount of leukaemia left after the previous phases of treatment.

The main treatments are:

• chemotherapy
• steroids

The drugs your child has during the intensification phase are usually the same as in induction and consolidation. Your child has most of their treatment as an outpatient. But they might have to stay in hospital for some parts.

Maintenance

Maintenance is the longest phase of treatment and lasts for 2 years from the end of induction. The treatment is much less intensive. It aims to keep the leukaemia away and prevent it from coming back (relapse). It mops up the few leukaemia cells that the other phases of treatment haven’t got rid of.

Your child has their maintenance treatment as an outpatient. The treatment is mainly chemotherapy. And treatment is tailored to your individual child’s blood counts.

High risk blocks

The high risk blocks use strong chemotherapy treatment. Your child has them after consolidation 1 if they have:

• a high number of leukaemia cells
• a high MRD result
• T-cell acute lymphoblastic leukaemia and do not respond to a chemotherapy drug called nelarabine

There are 3 high risk blocks and these last a total of around 10 weeks. Your child may have 2 rounds of high risk treatment.  

Side effects

Immediate side effects happen while they are having treatment or very soon after it finishes. The side effects depend on the treatments your child has. Some common side effects of acute lymphoblastic leukaemia treatment include:

• low resistance to infection
• anaemia - low red blood cell count
• risk of bruising and bleeding
• tiredness (fatigue)
• a sore mouth and tummy
• taste changes
• increased appetite while on steroids
• poor mobility and balance
• hair loss
• nausea and vomiting
• mood problems
• constipation

Your child might need to go into hospital to manage these side effects. This can happen when your child is mainly having outpatient treatment. The nurses will tell you what to look out for and when to call the hospital.

Their leukaemia treatment might be put on hold until they are well enough to start treatment again. This is common, but this change to family life and interruption to your child’s treatment can be difficult to cope with.