Leukemia--Chronic Myeloid (Myelogenous)

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Treating Leukemia - Chronic Myeloid (CML) TOPICS

Treating chronic myeloid leukemia by phase

Treatment options for people with chronic myeloid leukemia (CML) depend on the phase of their disease (chronic, accelerated, or blast phase), their age, other prognostic factors, and the availability of a stem cell donor with matching tissue type.

If you’d like more information on a drug used in your treatment or a specific drug mentioned in this section, see our Guide to Cancer Drugs , or call us with the names of the medicines you’re taking.

Chronic phase

The standard treatment for chronic phase CML is a tyrosine kinase inhibitor (TKI) such as imatinib (Gleevec), nilotinib (Tasigna), or dasatinib (Sprycel). For imatinib, the usual starting dose is 400 mg per day. If the first drug stops working (or it never really worked well at all) the dose may be increased or the patient may be switched to one of the other TKIs (including bosutinib). Ponatanib is an option after all of the other TKIs have been tried.

Switching to another TKI is also an option if the patient can't take the first drug because of side effects.

Some people in chronic phase may be treated with an allogeneic stem cell transplant (SCT). This treatment was discussed in detail in the section, "Stem cell transplant for chronic myeloid leukemia."

Monitoring treatment results

Monitoring the patient to see how they respond to treatment is very important. Blood counts are checked, and the blood may also be checked with a polymerase chain reaction (PCR) test to measure the amount of the BCR-ABL gene. The bone marrow may also be checked to see if the Philadelphia chromosome is there. Blood counts may be checked more often, but tests for the BCR-ABL gene or the Philadelphia chromosome are usually done about 3 months after treatment with a TKI is started. If the results show that treatment is working well, the patient may not need further testing for a few months. If the treatment isn’t working well, treatment may be changed.

Doctors look for different kinds of responses to treatment:

Hematologic response (usually happens within the first 3 months of treatment)

  • When blood cell counts return to normal, there are no immature cells seen in the blood, and the spleen has returned to normal size it is called a complete hematologic response (or CHR).
  • A partial hematologic response is similar to this, but not all of the above conditions are met.

Cytogenetic response (may take several months or longer)

  • A complete cytogenetic response (CCyR) occurs when no cells with the Philadelphia chromosome can be found in the blood or bone marrow.
  • A partial cytogenetic response (PCyR) occurs when less than 35% of cells still have the Philadelphia chromosome.
  • A major cytogenetic response (MCyR) includes both complete and partial responses
  • A minor cytogenetic response occurs when 35% to 90% of cells still have the Philadelphia chromosome.

Molecular response (this is based on the results of the PCR test)

  • A complete molecular response (CMR) means that the PCR test does not find the BCR-ABL gene in the patient's blood.
  • A major molecular response (MMR) means that the amount of BCR-ABL gene in the blood is very low.

Up to about 70% of people have a CCyR within 1 year of starting imatinib, and the rate of CCyR is even higher with the other TKIs (nilotinib and dasatanib). After a year, even more patients will have had a CCyR. Many of these patients also have a CMR.

But even if the BCR-ABL gene isn’t found, these people are probably not cured. For now, doctors recommend that people stay on the drug indefinitely.

If the first treatment doesn’t work

If the CML is responding well to treatment, at 3 months the patient should have a CHR and either some type of cytogenetic response or certain level of BCR-ABL on the PCR test. At 6 months, the patient should have at least a PCyR, and a CCR at 12 and 18 months. The patient should also have a MMR at 18 months.

If this doesn't happen, or if the leukemia gets worse, there are several options.

  • Increasing the dose of the drug. This helps some people, although the higher dose often has worse side effects.
  • Switching to another TKI, for example from imatinib to dasatinib, nilotinib, bosutinib, or ponatanib. The doctor may check the CML cells for genetic changes (mutations) to help decide what drug would be best.
  • Interferon or chemotherapy (chemo) may be tried for those who can't take these drugs or those for whom they are not working,
  • Stem cell transplant may be an option, especially for younger people who have a donor with a matching tissue type.

Treating CML after a stem cell transplant

Some people who have a stem cell transplant may not get a complete response. If they do not have graft-versus-host disease (GVHD), doctors may try to get their new immune system to fight the leukemia. One way to do this is by slowly lowering the doses or stopping the immune suppressing drugs they are taking. This is done very carefully in order to have an anti-leukemia effect without getting too much GVHD. Patients are watched closely during this time. Another approach that helps some patients is an infusion of lymphocytes taken from the person who donated the stem cells for the transplant. This can induce an immune reaction against the leukemia. Interferon may also be helpful.

In patients who do have GVHD after a stem cell transplant, boosting the immune system further is not likely to help. These patients are often treated with a TKI like imatinib.

Accelerated phase

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

The treatment options for accelerated phase CML depend on what treatments the patient has already had. In general, the options are similar to those for patients with chronic phase CML, but patients with accelerated phase CML are less likely to have a long-term response to any treatment.

If the patient hasn’t had any treatment, a TKI will be used. Imatinib (often at higher doses than used for chronic phase CML) is one option for most people. Most patients in this phase can respond to treatment with imatinib, but the responses do not seem to last as long as they do in patients in the chronic phase. Still, about half these patients are still alive after 4 years. The newer drugs like dasatinib and nilotinib are often used in this phase, and other drugs are under study.

If the patient is already getting imatinib, the dose may be increased. Another option is to switch to one of the other TKIs (dasatinib, nilotinib, or bosutinib). Sometimes the CML cells are tested to see if they have genetic changes (mutations) that may mean that a certain TKI is more or less likely to work (see the section “CML with the T315I mutation”). In CML without that mutation, ponatanib is an option after all of the other TKIs have been tried.

Interferon is another option, but it is also much less effective in this phase than in the chronic phase. About 20% of patients have some response to chemo, but these responses are usually shorter than 6 months.

An allogeneic stem cell transplant may be the best option for most patients who are young enough to be eligible. About 20% to 40% of patients with accelerated phase CML are alive several years after a stem cell transplant. Most doctors prefer that the leukemia be controlled, preferably in remission, before beginning the transplant procedure. To achieve this, chemo will often be used.

In some cases, an autologous SCT may be an option to try to get the CML back into the chronic phase, but it's very unlikely to result in a cure.

Blast phase

In the blast phase of CML, the leukemia cells become more abnormal. The disease acts like an acute leukemia, with blood counts getting higher and symptoms appearing or becoming more severe.

For people with blast phase CML who haven't been treated before, high-dose imatinib may be helpful, although it works in a smaller number of people and for shorter lengths of time than when used earlier in the course of the disease. The newer agents, dasatinib and nilotinib, seem to be better in this phase, particularly if they hadn't been used earlier. Bosutinib is also an option for patients who had previously been taking another TKI. Ponatanib may be used, but only after all of the other TKIs have been tried. Patients who respond to these drugs may still want to consider having a stem cell transplant, if possible.

Most often, the leukemia cells in this phase act like cells of acute myeloid leukemia (AML), but they are often resistant to the chemo drugs normally used to treat AML. Standard chemo for AML (see our document, Leukemia: Acute Myeloid (Myelogenous)) will bring about a remission in about 1 out of 5 patients, but this is usually short-lived. If this does occur, it may be a chance to consider some type of stem cell transplant.

A smaller number of patients have blast cells that act like cells of acute lymphoblastic leukemia (ALL). These cells are more sensitive to chemo drugs. Remissions can be induced in about half of these patients with drugs such as vincristine, prednisone, and doxorubicin, along with imatinib, if that hasn't been given yet. Like patients with ALL, these patients are at risk for having leukemia cells in the fluid that surrounds the brain and spinal cord, so they often get chemo (cytarabine or methotrexate) infused directly into that fluid (like during a spinal tap). Radiation therapy to the brain is another option but is used less often. For more information, see our document, Leukemia: Acute Lymphocytic.

Allogeneic SCT is less successful for blast phase CML than for earlier phases, and the long-term survival rate is less than 10%. Still, it is the only known option that may cure the disease. It is more likely to be effective if the CML can be brought back to the chronic phase before the transplant.

Because most patients with blast phase CML can't be cured, palliative treatment (intended to relieve symptoms rather than cure the disease) is important. Radiation therapy can help shrink an enlarged spleen or reduce pain from areas of bone damaged by leukemia. Chemo (usually with drugs such as hydroxyurea) may relieve some symptoms for a time.

Clinical trials of new combinations of chemo, targeted agents, and biologic therapies are important options.

CML with the T315I mutation

As was mentioned in the section about targeted therapy, in some patients on TKI treatment, the cancer cells develop a gene change called the T315I mutation that keeps most of the TKIs from working. If your CML stops responding to treatment with a TKI, another one may be tried. Your doctor may also check to see if the cancer cells have developed the T315I mutation. If they have, you may be switched to ponatinib, which is the only TKI that works against CML with this mutation. If this doesn’t work or you can’t take it because of side effects, you may be started on chemotherapy (chemo). Omacetaxine (Synribo) is a newer chemo drug that has been shown to help sometimes in this situation, but other chemo drugs may help as well.


Last Medical Review: 09/23/2013
Last Revised: 02/10/2014