Treatment for ALL that has not gone away with treatment or has come back

Leukaemia that does not go away with treatment is called refractory leukaemia. Leukaemia that comes back after treatment is called relapsed disease.  

It’s more difficult to treat relapsed or refractory acute lymphoblastic leukaemia (ALL). But there are treatments that your doctor can use to try to get you back into remission.

There are new treatments that have become available in recent years. These have improved a person's chance of getting into remission if they have relapsed or refractory ALL. 

Your choices

There may be one or several treatment options available to you. Your doctor will talk through each of these with you. This is important as it can help you make the right decision for you. Questions to ask or think about when talking about the treatments:

  • What are the side effects?

  • Will I need more tests?

  • What will the treatment involve? For example, how often do I have to go into hospital and how long for?

  • How will you know if this treatment is working and when do we check for this?

  • Do I have to stay overnight in hospital for this treatment?

  • Will this treatment cure the cancer?

  • What happens if I don’t have treatment?

What does treatment depend on?

The treatment you have depends on a number of factors including:

  • what type of ALL you have
  • if you have certain proteins on the surface of your leukaemia cells
  • how long you were in remission for
  • what treatment you had before
  • your age, general health and level of fitness

Treatment options

Your doctor may recommend you have one or more of the following:

  • more chemotherapy using different drugs to the ones you had before 
  • intensive chemotherapy with a stem cell transplant
  • a targeted cancer drug Open a glossary item such as a monoclonal antibody Open a glossary item
  • immunotherapy Open a glossary item, such as CAR T-cell therapy
  • treatment as part of a clinical trial

Find out about each of these below.

Chemotherapy

Chemotherapy drugs destroy cancer cells. The chemotherapy drugs circulate throughout your body in the bloodstream. The aim of this treatment is to get you into remission. Then you might have a stem cell transplant to prevent the leukaemia coming back.

It is likely that you will have a different type of chemotherapy than you had before.

The following is a list of some of the chemotherapy drugs that you might have:

  • fludarabine, cytarabine, G-CSF and idarubicin (FLAG – IDA)

  • nelarabine on it’s own

  • nelarabine with cyclophosphamide and etoposide if you have T cell ALL

Targeted cancer drugs

There are different types of targeted cancer drugs. For ALL, you might have:

  • tyrosine kinase inhibitors or TKIs
  • monoclonal antibodies or MABs

Tyrosine kinase inhibitors

The main type of targeted cancer drugs used for ALL are tyrosine kinase inhibitors or TKIs. They block signals from a protein called tyrosine kinase. Tyrosine kinases help to send growth signals in cells, so blocking them stops the cell growing and dividing.

You usually have a TKI called imatinib when you are first diagnosed with Philadelphia positive ALL (Ph+ ALL). And you continue to have it throughout treatment.

If your ALL comes back you might have a different TKI, such as:

  • dasatinib

  • ponatinib

You usually have your TKI with chemotherapy and steroids Open a glossary itemto get you back into remission. Sometimes you have a TKI alongside a monoclonal antibody such as blinatumomab.

We have specific information about each of these drugs on our cancer drugs A to Z list.

Monoclonal antibodies (MABs)

You might have a MAB if you have ALL that has come back or is not responding to treatment.

In ALL, they work by recognising and finding specific proteins on leukaemia cells. This helps the immune system to find and destroy them.

Some of the monoclonal antibodies you might have are:

  • blinatumomab

  • inotuzumab ozogamicin

Stem cell transplant

You might have a stem cell transplant. Having a transplant means destroying as many leukaemia cells as possible and replacing these with healthy stem cells. Open a glossary item

In ALL, you have the stem cells from someone else (a donor). This is known as an allogeneic transplant or allograft.  

Your donor might be:

  • a brother or sister (sibling match)

  • a person unrelated to you whose stem cells are similar to yours (matched unrelated donor or MUD)

In some cases you may have cord blood stem cells (from donated umbilical cord).  

Before you can move onto having your transplant your doctor checks how well the treatment has worked. If you have had a good response and you have a donor, you then start conditioning treatment. This treatment prepares your body to receive the stem cells.

There are two main types of conditioning treatment. These are:

  • myeloablative conditioning (MAC)

  • reduced intensity conditioning (RIC)

For myeloablative conditioning you have very high doses of chemotherapy. With reduced intensity conditioning you have lower doses of chemotherapy. You might also have other treatments such as radiotherapy to the whole body (total body irradiation or TBI Open a glossary item).

Conditioning treatment helps kill any remaining leukaemia cells as well as the healthy stem cells in your bone marrow. This makes space in your bone marrow for the donor stem cells. It also dampens down your immune system so you don’t reject the donor cells.

After the conditioning treatment you have the stem cells into your bloodstream through a drip. The cells find their way back to your bone marrow. Your body then starts making blood cells again and your bone marrow slowly recovers.

CAR T-cell therapy

CAR T-cell therapy is a type of immunotherapy Open a glossary item that is available on the NHS for some people with a type of ALL called B cell ALL.

You might have CAR T-cell therapy for one of the following reasons:

  • if you have relapsed ALL

  • if you have refractory ALL

  • as part of a clinical trial

If you are 25 years or under, you might have a CAR T-cell therapy drug called tisagenlecleucel (Kymriah).

If you are 26 years or older, you might have a CAR T-cell therapy drug called brexucabtagene autoleucel (Tecartus).

How does CAR T-cell therapy work?

White blood cells are an important part of your immune system. They help your body fight infections and other diseases, including cancer. T cells are a type of white blood cell. Their job is to move around your body, finding and destroying abnormal cells, like those from infections or diseases. When the cells find a new infection or disease, your body makes T cells to fight these abnormal cells.

Leukaemia cells are good at hiding from T cells so scientists are trying to find ways to get T cells to recognise the leukamia cells. One possible way to do this is CAR T-cell therapy.

With this treatment, a  specialist team takes a sample of T cells from your blood. This process is called apheresis (pronounced a-feh-ree-sis).

The T cells are then sent to the laboratory. In the laboratory, they change (modify) the T cells so that they can find and attack leukaemia cells in your body. You might hear this called genetically engineering the T cell. The T cell is now a CAR T-cell. CAR stands for chimeric antigen receptor. These CAR T-cells are designed to recognise and target a specific protein on the leukaemia cells.

These changed T cells grow and multiply in the laboratory. Once there are enough T cells you have a drip containing these cells back into your bloodstream. The aim is for the CAR T-cells to find and attack the leukaemia cells.

Clinical trials

Researchers are looking at how to improve treatment for people with ALL that hasn’t gone away or has come back. They do this through clinical trials.

Your doctor will be aware of current clinical trials. They will suggest a trial if there is anything that is right for your individual situation. Some of the treatments described above may only be available for you as part of a clinical trial such as CAR T-cell therapy.

We have information about UK clinical trials looking at treating ALL on our clinical trials database.

Coping with ALL that has come back or is not going away

There is support available to help you cope with the emotional, practical and physical issues of having leukaemia that is difficult to treat.

The uncertainty of not knowing if the treatment will work can be distressing. It will bring up a mixture of feelings that can be overwhelming for most people. There is no right or wrong way to deal with what you are going through. It might help to take each day as it comes.

There is information and support available to you, your family and friends. Some people find it can help to know more about their cancer and the treatments they might have. They like to plan ahead and think about what the future might look like. Other people don’t want to know what might happen. Many people find that knowing more about their situation can make it easier to cope.

Talk to your doctor or nurse to understand:

  • what your diagnosis means
  • what is likely to happen
  • what treatment is available
  • how treatment can help you

If you decide not to have treatment

You may decide not to have treatment such as chemotherapy. But you can still have medicines to help control symptoms.

Your doctor or nurse will explain what could help you. You can also ask them to refer you to a local symptom control team to give you support at home.

Cancer Research UK nurses

For support and information, you can call the Cancer Research UK information nurses. They can give advice about who can help you and what kind of support is available. Freephone: 0808 800 4040 - Monday to Friday, 9am to 5pm.
  • Acute lymphoblastic leukaemia in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow up
    D Hoezler and others
    Annals of Oncology, 2016. Volume 27, Supplement 5, Pages V69 to V82

  • ESMO Clinical Practice Guideline interim update on the use of targeted therapy in acute lymphoblastic leukaemia

    D Hoelzer and others

    Annals of oncology, 2023

  • Acute lymphoblastic leukaemia
    F Malard and M Mohty
    The Lancet, 2020. Volume 395, Issue 10230, Pages 1146 to 1162

  • NICE guidance on drugs for acute lymphoblastic leukaemia
    National Institute for Health and Care Excellence (NICE), accessed August 2024

  • SMC guidance on drugs for acute lymphoblastic leukaemia
    Scottish Medicines Consortium website, accessed August 2024

  • The information on this page is based on literature searches and specialist checking. We used many references and there are too many to list here. Please contact patientinformation@cancer.org.uk with details of the particular issue you are interested in if you need additional references for this information.

Last reviewed: 
26 Nov 2024
Next review due: 
26 Nov 2027

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