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

Refractory leukaemia is leukaemia that does not go away with treatment. 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 therapies that have become available in recent years. These new therapies 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 markers Open a glossary item are on the 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:

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

Find out about each of these below.

Chemotherapy

Chemotherapy drugs destroy cancer cells. The drugs circulate throughout your body in the bloodstream. The aim of chemotherapy is to get you into remission. Then you 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:

  • nelarabine with cyclophosphamide and etoposide if you have T cell ALL
  • fludarabine, cytarabine, G-CSF and idarubicin (FLAG – IDA)

Targeted cancer drugs

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

  • monoclonal antibodies or MABs
  • tyrosine kinase inhibitors or TKIs

Monoclonal antibodies (MABs)

You might have a monoclonal antibody if you have a type of ALL called precursor B cell ALL that has come back or is not responding to treatment.

Monoclonal antibodies work in different ways. 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 (Blincyto)
  • inotuzumab ozogamicin (Besponsa)

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

  • dasatinib (Sprycel)
  • ponatinib (Iclusig)

You usually have your TKI with chemotherapy and steroids Open a glossary item to 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.

Stem cell transplant

You might have a stem cell transplant. The aim of this treatment is to replace your stem cells Open a glossary item with new healthy stem cells from a donor. Your body can then make new blood cells that are healthy and able to fight against any remaining leukaemia cells.

A stem cell transplant uses stem cells from a donor’s bloodstream. You might sometimes hear it called a bone marrow transplant. A bone marrow transplant uses stem cells collected from a donor’s bone marrow Open a glossary item. These days you rarely have a bone marrow transplant as it is much easier to collect stem cells from the blood.

Before you can have a transplant, you first need treatment to get rid of as much leukaemia as possible. It also gives your doctor time to find you a donor for your transplant.

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 receive cord blood stem cells (from an 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
  • 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 new 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 if you're:

  • aged 25 or under and you have ALL that is not responding well to treatment (refractory)
  • aged 25 or under and have ALL that has come back (relapsed ALL)
  • any age, as part of a clinical trial

T cells are a type of white blood cell that moves around the body to find and destroy abnormal cells. When you come into contact with a new infection or disease, the body makes T cells to fight that specific infection or disease.

How does CAR T-cell therapy work?

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

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 cancer cells.

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

Tisagenlecleucel (Kymriah) is one of the current CAR T-cell therapies that you might have for ALL. Tisagenlecleucel is pronounced tis-a-jen-lek-loo-sel.

Clinical trial

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 if there is anything that is right for you based on your individual situation. Some of the treatments described above may only be available 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. You just have to take each day as it comes.

The important thing is to know that 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 cancer 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.
Last reviewed: 
27 Jul 2022
Next review due: 
27 Jul 2025
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    D Hoezler and others
    Annals of Oncology, 2016. Volume 27, Supplement 5, Pages V69 to V82

  • 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 June 2022

  • Cancer Drugs Fund
    NHS England website, last updated 17th June 2022
    Accessed June 2022

  • SMC guidance on drugs for acute lymphoblastic leukaemia
    Scottish Medicines Consortium website, accessed June 2022

  • 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.

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