Treatments for relapsed or refractory acute lymphoblastic leukemia

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Relapsed (or recurrent) acute lymphoblastic leukemia (ALL) is leukemia that has come back after being in remission from previous treatment.

Refractory ALL is leukemia that did not respond to treatment. This means that the previous treatments did not kill enough leukemia cells (blasts) to reach a complete remission.

You may be offered the following treatments for relapsed or refractory ALL. Your healthcare team will suggest treatments based on your needs and work with you to develop a treatment plan.

Immunotherapy

Immunotherapy helps to strengthen or restore the immune system’s ability to fight cancer. It is often used for relapsed or refractory B-cell ALL.

Types of immunotherapy used for ALL include monoclonal antibodies and CAR T-cell therapy.

Monoclonal antibodies

The monoclonal antibodies used for relapsed or refractory B-cell ALL trigger the immune system to attack and destroy leukemia cells. They are also considered a type of targeted therapy because they are made in a lab to recognize and lock onto particular protein markers on the surface of the leukemia cells.

Blinatumomab (Blincyto) may be given when the leukemia cells express (or produce) a protein called CD19 on their surface.

Inotuzumab ozogamicin (Besponsa) may be given when the leukemia cells express a protein called CD22 on their surface.

CAR T-cell therapy

CAR T-cell therapy is a type of immunotherapy that takes millions of T cells from a person with cancer. In the lab, they are changed so they have chimeric antigen receptors (CARs) on their surface. These receptors recognize a specific antigen (protein) found on the leukemia cells, which is most commonly CD19. The T cells are then given back to the person where they multiply, attack and destroy the leukemia cells.

Tisagenlecleucel (Kymriah) is a CAR T-cell therapy approved to treat young adults (up to age 25) with B-cell ALL that has not responded to other treatment or has come back after a stem cell transplant or other treatments. It may also be used to treat young adults with relapsed or refractory B-cell ALL who can't have a stem cell transplant.

Find out more about immunotherapy for ALL.

Chemotherapy

Chemotherapy uses drugs to destroy cancer cells. When it is given for relapsed and refractory ALL, it is called reinduction chemotherapy. Chemotherapy is the primary treatment for relapsed T-cell ALL, while immunotherapy is mainly used for relapsed B-cell ALL.

If ALL relapses after a long remission, it may respond to the drugs used in your original treatment. If ALL relapses after a short remission, doctors will use other drugs.

Refractory ALL may be treated with different drugs, or more intense doses of drugs that you have already received.

Find out more about chemotherapy for ALL.

Stem cell transplant

A stem cell transplant replaces stem cells, which are found in bone marrow, blood and umbilical cords. They are basic cells that develop into different types of cells that have different jobs. For example, all our blood cells develop from blood stem cells.

This treatment is used to replace stem cells when stem cells or bone marrow are damaged. A stem cell transplant is a complex treatment with many risks, and it must be done in a special transplant centre or hospital.

You may be offered a stem cell transplant:

  • after the leukemia relapses if another complete, or sometimes partial, remission is reached

  • if the leukemia did not fully respond to treatment and only a partial remission was ever reached

Find out more about a stem cell transplant for ALL.

Central nervous system prophylaxis or treatment

With ALL, leukemia cells can spread to the brain and spinal cord (called the central nervous system, or CNS). Treatment given to prevent leukemia cells from spreading to the CNS is called CNS prophylaxis. Treatments are also given if leukemia cells have already spread to the CNS.

You may receive one or more of the following as CNS prophylaxis or treatment for refractory or relapsed ALL:

  • intrathecal chemotherapy with methotrexate, cytarabine or a steroid such as prednisone
  • high-dose methotrexate given intravenously (through an IV)
  • radiation therapy to the brain and spinal cord

Intrathecal chemotherapy gives chemotherapy drugs directly into the cerebrospinal fluid (CSF), which is fluid around the brain and spinal cord. This type of chemotherapy is given through a lumbar puncture (also called a spinal tap) or an Ommaya reservoir.

Radiation therapy

Radiation therapy uses high-energy rays or particles to destroy cancer cells. External radiation therapy is the type of radiation therapy used to treat relapsed or refractory ALL.

You may receive radiation therapy to the brain as part of CNS prophylaxis. This type of radiation is also called cranial irradiation.

If a stem cell transplant is part of your treatment for relapsed or refractory ALL, you may receive radiation to your entire body first. This type of radiation is called total body irradiation (TBI).

Radiation therapy is also sometimes offered to relieve pain if the leukemia has spread to the bones.

Find out more about radiation therapy for ALL.

Targeted therapy

Targeted therapy uses drugs to target specific molecules (such as proteins) on cancer cells or inside them to stop the growth and spread of cancer.

Targeted therapy is a standard treatment for ALL if the leukemia cells have the Philadelphia chromosome (called Ph-positive ALL or Ph+ ALL). This happens when genetic material swaps between chromosomes 9 and 22, resulting in an abnormal chromosome and creating a new gene. The new gene is called BCR-ABL.

Ph+ ALL is first treated with chemotherapy and a targeted therapy drug called a tyrosine kinase inhibitor (TKI). The most common targeted therapy used to treat Ph+ ALL is imatinib (Gleevec).

But with relapsed or refractory Ph+ ALL, imatinib may not have worked or may have stopped working. If this happens, you will likely be switched to another targeted therapy drug, such as dasatinib (Sprycel) or ponatinib (Iclusig).

Certain monoclonal antibodies can also be used to treat refractory or relapsed B-cell ALL. Monoclonal antibodies are a type of targeted therapy, but they are also used as immunotherapy for ALL since they trigger the immune system to attack and destroy cancer cells.

Find out more about targeted therapy for ALL.

Supportive therapy

Supportive therapy is important during every phase of treatment for ALL. It is used to treat the complications that usually happen with treatments for ALL and complications from the leukemia itself.

Supportive therapies given during treatment for relapsed or refractory ALL may include:

  • antibiotics, antivirals or antifungals to prevent or fight infections
  • growth factors to help the bone marrow recover from chemotherapy and make more blood cells (chemotherapy can lower the white blood cell count, which increases your risk for infection)
  • transfusions of red blood cells, platelets, fresh frozen plasma and cryoprecipitate (a product that replaces clotting factors) as needed
  • drugs to bring down high levels of some substances in the blood that increase when many cancer cells die at the beginning of treatment (called tumour lysis syndrome)
  • leukapheresis to remove large numbers of white blood cells from the blood

Find out more about supportive therapy for ALL.

Clinical trials

Talk to your doctor about clinical trials open to people with ALL in Canada. Clinical trials look at new ways to prevent, find and treat cancer. Find out more about clinical trials.

Expert review and references

  • Kareem Jamani, MD, LMCC, FRCPC
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  • Amgen Canada. Product Monograph: Blincyto. https://pdf.hres.ca/dpd_pm/00060888.PDF.
  • Novartis Pharmaceuticals Canada Inc. . Product Monograph: Atriance. https://pdf.hres.ca/dpd_pm/00062403.PDF.
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