Treatments for relapsed or refractory acute myeloid leukemia

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Relapsed, or recurrent, acute myeloid leukemia (AML) means the leukemia has come back after treatment and remission.

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

Both relapsed and refractory AML need more treatment to reach complete remission.

Your healthcare team will suggest treatments based on your needs and work with you to develop a treatment plan. Some factors considered for your treatment include:

  • your age
  • your health
  • how long the leukemia was in remission
  • treatments you had before
  • where the leukemia comes back

Treatment options usually include chemotherapy and a stem cell transplant if possible. Targeted therapy may also be used.

Chemotherapy

Chemotherapy uses anticancer drugs to destroy cancer cells. Chemotherapy is the main treatment for relapsed or refractory AML. It may include repeating cycles of the same or similar drugs that were used in induction treatment if the complete remission was longer than one year. Similar or higher doses of the drugs may be used.

A repeat course of the 7-and-3 protocol may be given. In this protocol, cytarabine (Cytosar) is given continuously for 7 days with an anthracycline given for 3 days. The anthracyclines used in this protocol include:

  • daunorubicin (Cerubidine)
  • doxorubicin (Adriamycin)
  • idarubicin (Idamycin)
  • mitoxantrone (Novantrone)

Other types of chemotherapy combinations that may be offered for relapsed or refractory AML include:

  • FLAG – fludarabine (Fludara), cytarabine and filgrastim (Neupogen)
  • MEC – mitoxantrone (Novantrone), etoposide (Vepesid) and cytarabine
  • high-dose cytarabine (HDAC) and mitoxantrone
  • high-dose etoposide and cyclophosphamide (Cytoxan, Procytox)
  • cytarabine, daunorubicin and etoposide
  • clofarabine and cytarabine with or without filgrastim

Some people with relapsed or refractory AML are not strong enough to have intensive chemotherapy. If this is the case, you may be offered a less intensive chemotherapy regimen that includes one of these chemotherapy combinations:

  • azacitidine (Vidaza) with or without venetoclax (Venclexta)
  • decitabine (Dacogen, Demylocan, Inqovi) with or without venetoclax
  • clofarabine with or without cytarabine

Find out more about chemotherapy for AML.

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.

Some people with relapsed or refractory AML are not strong enough to have intensive chemotherapy. If this is the case, you may be offered targeted therapy.

  • If you have AML with the FLT3 mutation, you may be treated with gilteritinib (Xospata).
  • If you have AML with a CD33 protein marker, you may be treated with gemtuzumab ozogamicin (Mylotarg).
  • If you have AML with a mutated IDH2 gene, you may be treated with enasidenib (Idhifa).

Find out more about targeted therapy for AML.

Central nervous system treatment

The central nervous system (CNS) is the brain and spinal cord. If the leukemia has spread to the CNS, the treatment may include chemotherapy given directly into the spinal fluid (called intrathecal chemotherapy). The drug used in intrathecal chemotherapy is methotrexate or cytarabine. It is usually given during a lumbar puncture. Find out more about chemotherapy for AML.

Radiation therapy uses high-energy rays or particles to destroy cancer cells. Radiation therapy is sometimes given to the brain and spinal cord along with intrathecal chemotherapy. Find out more about radiation therapy for AML.

Stem cell transplant

A stem cell transplant replaces stem cells. In some cases, a stem cell transplant may be offered for relapsed or refractory AML. An allogeneic transplant is the preferred type of stem cell transplant. If a matched donor is not available, an autologous stem cell transplant may be an option.

A stem cell transplant may be offered to people who relapse soon after they reach a first complete remission or a second remission. People who relapse after a stem cell transplant may be offered other treatments, including an infusion of lymphocytes from their stem cell donor (called donor lymphocyte infusion, or DLI).

Find out more about a stem cell transplant for AML.

Radiation therapy

Radiation therapy uses high-energy rays or particles to destroy cancer cells. Radiation therapy may be given as part of the conditioning treatment before a stem cell transplant. It may also be used to treat AML that has spread to the central nervous system.

Find out more about radiation therapy for AML.

Supportive therapy

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

Supportive therapies given during treatment for relapsed or refractory AML 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)
  • 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

Find out more about supportive therapy.

Clinical trials

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

Expert review and references

  • Robert Turner, MD, FRCPC
  • John Storring, MD, CM
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  • PDQ® Adult Treatment Editorial Board. Acute Myeloid Leukemia Treatment (PDQ®) – Health Professional Version. Bethesda, MD: National Cancer Institute; 2021: https://www.cancer.gov/.
  • Provincial Health Services Authority. BC Cancer Protocol Summary: Treatment of Acute Myeloid Leukemia using Gemtuzumab Ozogamicin with Induction and Consolidation Chemotherapy. Vancouver, BC: 2021: http://www.bccancer.bc.ca/.
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