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If you have chronic myeloid leukemia (CML), your treatment options will depend on:

• The phase of your disease (chronic, accelerated, or blast phase)
• Your age, overall health, and preferences
• Other prognostic factors (including the risk score for chronic phase CML)
• The availability of a stem cell donor with a matching tissue type (for a possible stem cell transplant)

Treating chronic phase CML

In most people, CML is in the chronic phase when it is first diagnosed.

Initial treatment for chronic phase CML

The standard first treatment for chronic phase CML is a targeted drug known as a tyrosine kinase inhibitor (TKI). Options might include:

• Imatinib (Gleevec, Imkeldi)
• Nilotinib (Tasigna, Danziten)
• Dasatinib (Sprycel)
• Bosutinib (Bosulif)
• Asciminib (Scemblix)

These medicines are all taken by mouth, and they need to be taken daily.

Some important factors for you and your cancer care team to consider when choosing among these drugs include:

• CML risk score: In general, any of these drugs can be used first for people with low-risk chronic phase CML. But imatinib isn’t usually a first choice for intermediate- or high-risk CML, which is more likely to progress to a more advanced phase.
• Your overall health: The medicines can have different side effects. Depending on your other health issues, some might be better options for you than others.
• What medicines you take: These drugs can interact with many other medicines. This might be a consideration when choosing a drug.
• BCR::ABL1 mutations: If the CML cells have certain changes (mutations) in the BCR::ABL1 gene (and therefore the BCR::ABL1 protein), some of these drugs might be more likely to work than others. If it looks like one of these drugs is no longer helping you, your doctor might test for these changes in your CML cells.
• The goal of treatment: If the goal is to get to a treatment-free remission (where a trial of stopping the medicine can be done), this might affect the choice of drug. Some TKIs are more likely than others to result in deep remissions.

Stem cell transplant for chronic phase CML

Rarely, people in chronic phase may be treated with an allogeneic stem cell transplant, because it offers the best chance to cure CML (although it also can have serious side effects).

This is more likely to be considered in children and young adults with CML who have a matched stem cell donor available. This treatment is discussed in Stem Cell Transplant for Chronic Myeloid Leukemia.

Treating CML during pregnancy

TKIs are usually very effective in treating CML, but they’re typically not used during pregnancy because they might harm the fetus. Interferon can often be used to treat CML during pregnancy, and a TKI can be started (or restarted) later on.

Monitoring treatment results

Monitoring for a response is a very important part of CML treatment.

Your blood cell counts will be checked often. The blood is also checked regularly with a polymerase chain reaction (PCR) test to measure the amount of the BCR::ABL1 gene, with the results reported according to the International Scale.

Your bone marrow will also be checked to see if the Philadelphia chromosome is there.

Testing for the BCR::ABL1 gene or the Philadelphia chromosome is usually done about 3 months after a TKI is started, and then every 3 to 6 months after that. Ideally, the response to treatment should be within certain time frames.

Meeting certain milestones tends to be linked to more favorable outcomes.

Three months after starting treatment:

• No more than 35% of the cells in the bone marrow should have the Philadelphia chromosome (major cytogenetic response)
• The level of BCR::ABL1 should be no more than 10% (1/10^th) of a standardized level at the time of diagnosis (early molecular response)

Six months after starting treatment:

• There should be no evidence of cells in the bone marrow with the Philadelphia chromosome (complete cytogenetic response)
• The level of BCR::ABL1 should be no more than 1% (1/100^th) of what it was at the time of diagnosis

Twelve months after starting treatment:

• The level of BCR::ABL1 should be no more than 0.1% (1/1,000th) of what it was at the time of diagnosis (major molecular response)

If these milestones are met (meaning test results show treatment is working well) a person typically stays on their current TKI.

If you are taking the drug as directed and test results show treatment isn’t working well, your cancer care team may do more tests to see what’s going on. A different TKI (or possibly a different treatment) may need to be considered.

For more on the different types of responses to treatment, see How Do You Know If Treatment for Chronic Myeloid Leukemia Is Working?

Considering stopping treatment for chronic phase CML

Most people in chronic phase CML have good responses to treatment. But even if the BCR::ABL1 gene can no longer be detected, it’s often not clear if a person is cured, so most people need to continue taking a TKI daily.

Like many drugs used to treat cancer, TKIs can have bothersome side effects. In some people who have a deep, long-lasting response to treatment, doctors might suggest stopping the drug for a time and closely monitoring with blood tests to see if the CML returns.

In general, this might be an option in adults with chronic phase CML who:

• Have been on a TKI for at least 3 years
• Have had a stable molecular response (a deep molecular response lasting at least 2 years)
• Are willing to undergo frequent testing for signs of the CML returning

If the CML does return after stopping the TKI, it typically responds well when the original treatment is restarted in a timely fashion.

If the first treatment doesn’t work (or if side effects are an issue)

If the leukemia doesn’t respond well to the first TKI, or if you can't take the TKI because of side effects or other problems, your cancer care team might suggest other options, including:

• Changing the dose of the TKI. Increasing the dose in certain situations might help some people get a response to treatment. But higher doses often have worse side effects. On the other hand, if side effects are the issue, lowering the dose of the TKI might be an option.
• Switching to another TKI, for example from imatinib to a second-generation TKI like dasatinib, nilotinib, or bosutinib. Your doctor will likely do a mutational analysis to check your CML cells for changes (mutations) in the BCR::ABL1 gene. This can help them decide which drug(s) are the best options.
• Switching to interferon. This may be tried if you can't take TKIs for some reason, or if TKIs aren’t working.
• Getting a stem cell transplant. This may be an option, especially for younger people who have a donor with a matching tissue type.

Treating CML with the T315I mutation

When a person takes a TKI, the CML cells sometimes develop the T315I mutation in the BCR::ABL1 gene. This stops most TKIs from working.

If your CML stops responding to treatment with a TKI, your doctor may check to see if the CML cells have developed this mutation.

If they have, you may be switched to a TKI that works against CML cells with the T315I mutation, such as ponatinib (Iclusig) or asciminib.

Treating CML after a stem cell transplant

The goal of a stem cell transplant for CML is to cure the disease. If CML is cured, no further treatment should be needed. But some people may not get a complete response to the transplant.

If you don’t have graft-versus-host disease

If you do not have graft-versus-host disease (GVHD), your cancer care team may try to get your new immune system to fight the leukemia.

One way to do this is by stopping or slowly lowering the doses of your immune suppressing drugs. This is done very carefully in order to have an anti-leukemia effect without getting too much GVHD. You will be watched closely during this time.

Another approach that helps some people is an infusion of lymphocytes taken from the person who donated the stem cells for the transplant. This is called a donor lymphocyte infusion. It can prompt an immune reaction against the CML cells.

Treatment with other drugs may also be helpful.

If you have graft-versus-host disease

If you do have GVHD after a stem cell transplant, boosting your immune system further isn’t likely to help. In this case, people are often treated with a TKI.

In either situation, you might consider taking part in a clinical trial of newer treatments that might be helpful.

Treating accelerated phase CML

When CML is in accelerated phase, leukemia cells begin to build up in the body quickly, causing symptoms. The leukemia cells often have more gene mutations than in chronic phase CML. These mutations help them grow and might make treatments less effective.

Accelerated phase CML can develop from chronic phase CML, or it can develop on its own.

The treatment options for accelerated phase CML depend on:

• What treatments you’ve already had, if any
• Other factors, like if the CML cells have certain BCR::ABL1 gene mutations
• Your overall health and preferences

In general, the options are a lot like those for chronic phase CML, but people with accelerated phase CML are less likely to have a long-term response to treatment.

Treating accelerated phase CML that arises on its own

If you haven’t had any treatment for CML, a targeted drug known as a tyrosine kinase inhibitor (TKI) is typically the first treatment.

A second generation TKI like dasatinib, nilotinib, or bosutinib is often used first in this phase. Other TKIs such as imatinib, ponatinib, and asciminib might be options as well. If one of these drugs stops working, another can be tried.

Treating accelerated phase CML that develops from chronic phase CML

If you are already taking a TKI when chronic phase CML goes into the accelerated phase, switching to one of the other TKIs is typically the next step. The CML cells might be tested to see if they have certain BCR::ABL1 gene changes (mutations) that would mean certain TKIs are more or less likely to work.

If one of the TKIs stops working, another can be tried.

Stem cell transplant and other treatment options

An allogeneic stem cell transplant may be an option at some point for most people who are young and healthy enough to have this treatment and who have a matched stem cell donor available.

This might be considered earlier in the course of treatment if the accelerated phase CML has developed from chronic phase CML. (For more on possible options after this, see “Treating CML after a stem cell transplant,” above.)

Other treatment options might include interferon or adding a chemotherapy drug to the TKI, although these are less likely to result in long-term remissions.

Treating blast phase CML

In the blast phase of CML, the leukemia cells are more abnormal, and the disease acts like an acute (fast-growing) leukemia, with blood counts getting higher quickly and symptoms appearing or getting worse.

Most often, blast phase CML starts out as chronic phase CML that progresses over time. But in a small percentage of cases, CML is in blast phase when it’s first diagnosed.

Overview of treatment of blast phase CML

As with other phases of CML, targeted drugs called tyrosine kinase inhibitors (TKIs) are an important part of the treatment for blast phase CML. But these drugs often aren’t as effective in this phase, so other treatments such as chemotherapy are typically used as well.

Blast phase CML is often treated similarly to an acute leukemia. When possible, treatment includes intense chemotherapy plus a TKI to try to get the CML into remission. If you are eligible, a stem cell transplant is typically done at this point, as it offers the best chance for long-term survival.

Choice of TKI for blast phase CML

A second generation TKI like dasatinib, nilotinib, or bosutinib is often used first in blast phase CML. Other TKIs such as ponatinib and asciminib might also be an option. Imatinib isn’t used as often because it’s less likely to be effective, and if it does work, it usually takes longer to do so.

Treating myeloid blast phase CML

Most often, the leukemia cells in blast phase CML act like cells of acute myeloid leukemia (AML). Treatment usually includes the same type of intense chemo used to treat AML, plus a TKI. If you aren’t healthy enough for intense chemo, a TKI might be used by itself.

If the CML can be put into remission, a stem cell transplant is done at this point, if possible. (For more on possible options after this, see “Treating CML after a stem cell transplant,” above.)

If you aren’t eligible for a stem cell transplant, you might get more chemo, followed by long-term use of a TKI.

Treating lymphoid blast phase CML

A smaller number of people with blast phase CML have cells that act like cells of acute lymphoblastic leukemia (ALL). Treatment usually includes the same type of intense chemo used to treat ALL, plus a TKI. If you aren’t healthy enough for intense chemo, a TKI might be given along with a steroid drug instead.

If the CML can be put into remission, a stem cell transplant is done at this point, if possible. (For more on possible options after this, see “Treating CML after a stem cell transplant,” above.)

If you aren’t eligible for a stem cell transplant, you might get more chemo, followed by long-term use of a TKI.

Supportive or palliative treatment for CML

No matter what phase your CML is in, supportive treatments might be helpful. You might also hear this called palliative care. This type of treatment is aimed at preventing or relieving symptoms, rather than treating the leukemia directly.

For example, radiation therapy might be used to help shrink an enlarged spleen or reduce pain from areas of bone damaged by leukemia. Blood transfusions might be given to raise your blood cell counts.

Supportive care treatments are often an important part of the overall treatment plan. They are often used along with treatments aimed at the CML itself.

Considering a clinical trial

CML can often be treated effectively, especially in the chronic phase. Still, current treatments aren’t helpful for everyone with CML, and newer treatments are still needed.

Clinical trials of new combinations of targeted drugs, chemotherapy, and other types of drugs are important options for treating all phases of CML. Talk to your cancer care team if you want to explore clinical trials as a treatment option.