Treatments for relapsed or refractory acute lymphocytic leukemia

Relapsed, or recurrent, acute lymphocytic leukemia (ALL) means the leukemia has come back after treatment and reaching remission. Treatment for relapsed ALL is usually given for 2–3 years.

Refractory disease means the leukemia did not respond to treatment. Complete remission has not been reached because the chemotherapy drugs did not kill enough leukemia cells, or blasts.

Both relapsed and refractory ALL need more treatment to reach a remission. The following are treatment options for relapsed or refractory ALL.


Chemotherapy is the primary treatment for relapsed and refractory ALL. When it is given for relapsed and refractory ALL, it is called reinduction chemotherapy.

If ALL relapses after a long remission, it may respond to the drugs used in the 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 have already been given.

Drugs that may be used in combination to treat relapsed or refractory ALL include:

  • vincristine (Oncovin)
  • daunorubicin (Cerubidine, daunomycin) or doxorubicin (Adriamycin)
  • cytarabine (Cytosar, Ara-C)
  • asparaginase (Kidrolase)
  • etoposide (Vepesid, VP-16)
  • teniposide (Vumon, VM-26)
  • mercaptopurine (Purinethol, 6-MP)
  • methotrexate
  • cyclophosphamide (Cytoxan, Procytox)
  • steroids such as prednisone or dexamethasone (Decadron, Dexasone)

Targeted therapy

Targeted therapy is treatment that uses drugs or other substances to target specific molecules (usually proteins) involved in cancer cell growth while limiting harm to normal cells.

People with leukemia cells that have the Philadelphia chromosome (called Ph+ ALL) are often given imatinib (Gleevec). Ph+ ALL can become resistant to imatinib, so these people are often switched to another targeted therapy.

Blinatumomab (Blincyto) may be given for Ph+ precursor B ALL, and with leukemia cells that have don’t have the Philadelphia chromosome (called Ph- ALL).

Inotuzumab ozogamicin (Besponsa) may be given to people with relapsed or refractory CD22-positive B-cell precursor ALL.

Radiation therapy

Low-dose external beam radiation therapy may be given to help relieve symptoms caused by the spread of ALL to the bone or brain and spinal cord (called the central nervous system, or CNS).

Central nervous system prophylaxis or treatment

The central nervous system (CNS) is the brain and spinal cord. Treatment given to prevent the leukemia cells from spreading to the CNS is called CNS prophylaxis. Treatments are also given if ALL has spread to the CNS.

CNS prophylaxis or treatment may include one or more of the following:

  • chemotherapy given directly into the spinal fluid (called intrathecal chemotherapy) with methotrexate, cytarabine or a steroid such as prednisone
  • high-dose methotrexate given intravenously
  • radiation therapy to the brain

Stem cell transplant

An allogeneic stem cell transplant is generally recommended if ALL comes back after a second remission is reached. Sometimes a stem cell transplant is offered if only a partial remission is reached.


Immunotherapy helps to strengthen or restore the immune system’s ability to fight cancer. 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. 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 stem cell transplant or other treatments. It may also be used to treat young adults with B-cell ALL that are unable to have a stem cell transplant.

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 the disease 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 (chemotherapy can affect the bone marrow so it doesn’t make enough healthy blood cells, which can increase the 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 chemicals 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

Clinical trials

You may be asked if you want to join a clinical trial for ALL. Find out more about clinical trials.

Expert review and references