If your B-ALL treatment isn’t working or the B-ALL has come back

• Tyrosine Kinase Inhibitors (TKIs): If you have Philadelphia positive B-ALL, your hospital team may offer you a different TKI. You may have this alongside immunotherapy and/or more chemotherapy.
  
• The TKI that most people with Ph+ B-ALL have when they first start treatment, is imatinib. If this stops working for you, or does not get you into remission, there are other TKIs that can be tried. TKIs that can be used for people who have relapsed or refractory Philadelphia positive B-ALL include dasatinib and ponatinib.
  
• Blinatumomab: Unless you have Ph+ B-ALL, you may be given a drug called blinatumomab,  if you haven’t had it before. Blinatumomab can be used to treat B-ALL that either remains in the bone marrow after intensive chemotherapy (refractory B-ALL) or comes back after a period of remission (relapsed B-ALL).
  
  Blinatumomab is a type of immunotherapy, which means it uses your immune system to destroy leukaemia cells. Research has found that treatment plans including blinatumomab can lead to more people with relapsed or refractory Ph- B-ALL reaching remission, than those who were given traditional chemotherapy alone.
  
• Inotuzumab ozogamicin: This is a type of monoclonal antibody drug with chemotherapy attached to it. It targets a protein called CD22, which is found on the surface of leukaemia cells in some people with B-ALL.
  
  At the moment, it is only offered to people whose B-ALL has relapsed or is refractory to other treatments and whose leukaemia cells have the CD22 protein.

These days, chemotherapy is used less often on its own for relapsed or refractory B-ALL. This is because newer, targeted treatments have been found to be more effective, and for many people, often have fewer side effects. Therefore, you may still have chemotherapy, but this will usually be given alongside other types of treatment. Depending on your treatment plan, chemotherapy may be given as:

Re-induction therapy – to try to get your B-ALL back into remission after it has come back (relapsed) or has not responded to previous treatment.

Bridging therapy – to help control your B-ALL while you are preparing for another treatment, such as a stem cell transplant or CAR-T therapy.

You may have a chemotherapy combination called FLAG or FLAG-ida.

• fludarabine – a type of chemotherapy drug
• cytarabine – a type of chemotherapy drug
• G-CSF – you might be given a drug called a growth factor, which helps your bone marrow to make more neutrophils (a type of white blood cell that helps fight infection).

You might also receive idarubicin, another type of chemotherapy drug, as part of a more intensive treatment protocol called FLAG-Ida.

You may be told that you will need a donor stem cell transplant to give you the best chance of staying in remission long-term. A stem cell transplant aims to completely replace your immune system and your bone marrow, so they can work normally again.

Your doctor will look at many different things before deciding whether to recommend a stem cell transplant, including:

• whether you have a suitable donor (from a brother, sister, or somebody not related to you)
• the risk of the B-ALL coming back
• whether the B-ALL has any genetic changes
• how well the B-ALL has responded to previous treatments.

They will also consider your overall fitness. This helps them understand how well your body is likely to cope with the treatment. A stem cell transplant is a very intensive treatment, so it is not right for everybody.

You will only be offered a stem cell transplant if your hospital team thinks that there is a higher chance of you going into remission, than having serious complications.

Order our information booklet on donor stem cell transplants: Allogeneic (donor) stem cell transplants: the seven steps

Some people who have relapsed or refractory B-ALL, may be able to have a treatment called CAR T-cell therapy.
CAR T-cell therapy is a type of immunotherapy, which means it works by using someone’s own immune system to kill the cancer cells in their body.

How does CAR T-cell therapy work?

T cells (blood cells that help fight and prevent infection) will be taken from your blood, using a tube inserted into a vein in your arm, through a process called apheresis. Your T-cells will then be sent to a lab, where their DNA will be altered to give them the ability to recognise and kill cancer cells. These newly modified cells are called CAR T-cells.

Over the next few weeks, the lab will grow lots of these CAR T-cells. While you are waiting for your new CAR T-cells, you might receive another type of treatment, such as chemotherapy, to help control the B-ALL before your CAR T-cell therapy. This is known as bridging treatment.

Once enough CAR T-cells have been grown in the lab, they are then put back into your bloodstream, so that they can get to work finding and destroying the cancer cells in your body.

Afterwards, you will be closely monitored by your hospital team for the next few weeks. Most people having CAR T-cell therapy need to stay in hospital for between 10 and 28 days.

CAR T-cell therapy for B-ALL

Car T-cell therapy has strict eligibility criteria. At the moment, the below CAR-T treatments are approved in the UK for B-ALL:

• Aucatzyl (obe-cel or obecabtagene autoleucel). This is approved for people aged 26 years of age and over, who have relapsed or refractory B‑cell ALL.
• Tisagenlecleucel (Kymriah®) This is approved for people aged 25 years of age and under who have B‑cell ALL that is not responding to treatment, has relapsed after a stem cell transplant or is in a second or later relapse.
• Brexucabtagene autoleucel (Tecartus®) - this is approved for people aged 26 years of age and over, who have relapsed or refractory B-ALL.