Treatments for refractory chronic myeloid leukemia

Refractory chronic myeloid leukemia (CML) means that the number of granulocytes with the BCR-ABL gene (leukemia cells or CML cells) that are in the blood has increased after treatment.

There are 2 types of refractory CML.

• Primary refractory disease means that CML hasn't responded to any treatment.
• Secondary refractory disease means that CML has stopped responding to treatment.

The following are treatment options for refractory CML. Your healthcare team will suggest treatments based on the type of refractory disease and your needs. They will work with you to develop a treatment plan.

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.

The type of targeted therapy drugs offered for refractory CML are tyrosine kinase inhibitors (TKIs).

To decide which TKI might work best, your healthcare team may order blood or bone marrow tests to see if the blast cells have genetic changes in addition to the BCR-ABL gene. These are called additional chromosome abnormalities (ACAs). Most TKIs do not work for CML with ACAs.

If you are already taking a TKI, the dose may be increased, or you may be offered a different TKI.

The TKI drugs that may be used for relapsed or refractory CML are:

• dasatinib (Sprycel)
• nilotinib (Tasigna)
• bosutinib (Bosulif)
• imatinib (Gleevec)
• ponatinib (Iclusig), which may be given for CML with genetic changes other than the BCR-ABL gene

Find out more about targeted therapy for CML.

A stem cell transplant replaces stem cells. This treatment is only offered for refractory CML if you have never had a stem cell transplant before.

The type of stem cell transplant that may be offered is called an allogeneic stem cell transplant. It uses stem cells from a matched donor.

Before the transplant, targeted therapy drugs are used to try to improve the blood cell counts.

If a stem cell transplant doesn't effectively treat refractory CML, you may be given a donor lymphocyte infusion (DLI). Before a stem cell transplant, lymphocytes are removed from the donor’s blood and frozen for storage. The lymphocytes are thawed and are given through one or more infusions. It may boost the immune system and bring on a stronger immune reaction against the leukemia cells.

Find out more about a stem cell transplant for CML.

Chemotherapy uses drugs to destroy cancer cells. It may be offered if CML no longer responds to targeted therapy or if TKIs cause severe side effects. Chemotherapy is also used in preparation for a stem cell transplant, if you are offered this treatment.

The chemotherapy drugs used to treat refractory CML that is resistant to TKIs include:

• hydroxyurea
• cytarabine
• hyperfractionated CVAD (cyclophosphamide, vincristine, doxorubicin and dexamethasome)

When deciding which chemotherapy drugs to offer, your healthcare team may order blood or bone marrow tests to see if CML has changed. The blast cells may have genetic changes in addition to the BCR-ABL gene. They may also look or act like other types of leukemia cells.

If CML changes to look like acute myeloid leukemia (AML), chemotherapy for AML may be offered.

If CML changes to look like acute lymphoblastic leukemia (ALL), chemotherapy for ALL may be offered.

Find out more about chemotherapy for CML.

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