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.

Chronic phase

The standard treatment for chronic phase CML is a tyrosine kinase inhibitor (TKI), and imatinib (Gleevec) is the first choice. The usual starting dose is 400 mg per day. If this drug stops working (or it never really worked well at all) the dose may be increased. Another option is to use one of the other TKIs, such as dasatinib or nilotinib. These drugs are also used if the patient can't take imatinib due to 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, "How is chronic myeloid leukemia treated?"

Monitoring treatment results: Monitoring the patient's blood and bone marrow for a response is a very important part of treatment. It is usually done every 3 to 6 months for the first 2 years after starting imatinib. Blood counts are watched closely, and the blood and bone marrow are looked at to see if the Philadelphia chromosome is there. If the Philadelphia chromosome isn't found, the polymerase chain reaction (PCR) test, which is very sensitive, may be used to see if small amounts of bcr-abl are still present. 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 see 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 occurs when less than 35% of cells still have 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 Philadelphia chromosome.

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

• A complete molecular response (CMR) means that the PCR test cannot find bcr-abl in the patient's blood.

• A major molecular response (MMR) means that the amount of bcr-abl in the blood is very low.

About 90% of people have a complete cytogenetic response within 5 years of starting imatinib. But even if the abnormal chromosome can't be seen, these people are probably not cured. For now, doctors recommend that people stay on the drug indefinitely.

Other treatments: The goal of treatment with imatinib is a complete hematologic response plus a complete cytogenetic response. If this doesn't happen, or if the leukemia gets worse, there are several options.

• Increasing the dose of imatinib. This helps some people, although the higher dose often has worse side effects.

• Using other TKIs, like dasatinib (Sprycel) and nilotinib (Tasigna).

• For those who can't take these drugs or for whom they are not working, interferon or chemotherapy may be tried.

• 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 achieve 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 on. 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 a donor lymphocyte infusion (DLI), where the patient receives 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. Imatinib and interferon are other options that may 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 imatinib.

Accelerated phase

During the accelerated phase, leukemia cells begin to build up in the body more quickly, which causes symptoms. The leukemia cells often acquire new gene mutations, which help them grow and tend to 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.

Imatinib (often at higher doses than used for chronic phase CML) is an 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. 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 chemotherapy, 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, chemotherapy 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. 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 chemotherapy drugs normally used to treat AML. Standard chemotherapy for AML (see our document, Acute Myeloid Leukemia) 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 chemotherapy 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. These patients are at risk for spread to the central nervous system, so they often get chemotherapy (cytarabine; Ara-C or methotrexate) infusions in the spinal fluid. Radiation therapy to the brain is another option but is used less often.

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. Chemotherapy (usually with drugs such as hydroxyurea) may relieve some symptoms for a time.

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

Last Medical Review: 11/05/2009
Last Revised: 11/05/2009