The treatment of CML depends on the phase of the disease and the patient’s overall health. In many cases, a team of doctors will work with the patient to determine the best treatment plan.
This section outlines treatments that are the standard of care (the best treatments available) for this specific type of cancer. Patients are also encouraged to consider clinical trials as a treatment option when making treatment plan decisions. A clinical trial is a research study to test a new treatment to prove it is safe, effective, and possibly better than standard treatment. Your doctor can help you review all treatment options. For more information, visit the Clinical Trials section.
Tyrosine kinase inhibitors
These drugs are a type of targeted therapy, which is treatment that targets faulty genes or proteins that contribute to cancer growth and development. In this case, the target is a specialized protein called the tyrosine kinase enzyme that is involved in CML.
Imatinib
Imatinib (Gleevec) was approved by the U.S. Food and Drug Administration (FDA) for the treatment of all phases of CML in 2001. This drug has the unique ability to specifically inhibit the action of the BCR-ABL enzyme, which in turn results in the rapid death of the CML cells.
This drug has changed standard treatment for CML. It is given in pill form once or twice a day and causes fewer side effects than previous treatments. Nearly all patients in the chronic stage respond to the drug with complete normalization of blood counts and shrinkage of the spleen. Most importantly, the cells with the Philadelphia chromosome are eliminated, as assessed by cytogenetic studies, in 80% to 90% of newly diagnosed patients in the chronic phase. This is called a complete cytogenetic remission (CCyR).
The recurrence rate in patients whose cancer completely responds to imatinib has been very low, and it is now clear that patients with a significant reduction in the Philadelphia chromosome will remain in chronic phase longer with imatinib, compared with previous therapies. Although it is too soon to know how long these responses will last or if patients will be cured with this medication alone, there are patients who have been successfully treated with imatinib since its introduction in clinical trials in 1999.
Imatinib is now considered the treatment of choice for chronic phase CML, although bone marrow transplantation may also be a primary treatment option for younger patients (see below). Side effects of imatinib are mild but can include slight nausea, changes in blood counts, fluid retention, swelling around the eyes, and muscle cramps. If a patient’s CML responds well to imatinib (there is no evidence of the Philadelphia chromosome and the patient has a normal level of blood cell counts), the patient should stay on this medication indefinitely.
Dasatinib
In 2006, the FDA approved dasatinib (Sprycel) for the treatment of adults with CML and Philadelphia-positive acute lymphocytic leukemia (ALL) when previous treatment, including imatinib, did not work, stopped working, or could not be given. Dasatinib is a pill that may be taken once or twice a day, depending on the dose.
The side effects of dasatinib include anemia, neutropenia (low levels of white blood cells), thrombocytopenia (low platelet counts), and fluid around the lungs. Health-care providers will monitor the patient’s blood counts frequently after starting dasatinib and may adjust dosing or stop giving the drug temporarily if the patient’s blood counts drop too low. Dasatinib may also cause bleeding, fluid retention, diarrhea, rash, headache, fatigue, andnausea.
Nilotinib
In 2007, the FDA approved nilotinib (Tasigna) for patients with Philadelphia chromosome-positive chronic phase or accelerated phase CML, when previous treatment, including imatinib, did not work, stopped working, or could not be given. Nilotinib is in the form of a capsule that patients take by mouth. The most serious side effect of nilotinib includes possible life-threatening heart problems that can lead to an irregular heartbeat and possible sudden death. However, this side effect is rare. Common side effects include low blood counts, rash, headache, nausea, and itching. Other possible serious side effects include liver damage, fluid accumulation, and inflammation of the pancreas.
It is important for people taking imatinib, dasatinib, or nilotinib to take the medication on a regular basis, to delay the development of disease resistance to these drugs. Talk with your doctor for more information.
Measuring treatment effectiveness
Patients receiving treatment with any of these drugs should be regularly monitored to see how well the treatment is working. The response of CML includes:
- A complete hematologic response: the white blood cell and platelet counts have returned to normal, the spleen is of normal size and cannot be felt on physical examination, and the patient has no symptoms of CML
- A partial response: the blood counts are still abnormal, there may still be some immature blasts present in the blood, and the spleen may still be enlarged, but the symptoms and blood tests are improved compared with those before treatment
Other specific tests are used to detect the number of cells that have the Philadelphia chromosome or contain the BCR-ABL fusion gene. At diagnosis, the Philadelphia chromosome is present in almost all of the marrow cells. Once a patient’s cancer shows a complete hematologic response, the doctor then measures the cancer’s cytogenetic response.
- A complete cytogenetic response means there are no cells with the Philadelphia chromosome detected by cytogenetic analysis.
- A partial cytogenetic response means that between 1% and 34% of the cells still have the Philadelphia chromosome.
- A minor cytogenetic response means that more than 35% of the cells still have the Philadelphia chromosome.
The goal of treatment is to achieve a complete cytogenetic response evaluated by performing a bone marrow biopsy, when other tests such as FISH done on a sample of the patient’s blood, suggest that the Philadelphia chromosome has been markedly reduced.
Other more sensitive tests include FISH and PCR (see Diagnosis section), which can be done on a blood sample and are typically performed several times a year. Patients who have no cells with the Philadelphia chromosome by regular cytogenetic analysis are often monitored by the PCR test with the goal of a molecular response.
Sometimes, a tyrosine kinase drug stops working and the CML develops resistance to it. Apparent resistance can occur if patients do not take their medication regularly, as prescribed. Even in patients who do take the medication appropriately, the CML may become resistant to imatinib, which is why it is important to monitor the cancer with cytogenetics, FISH, or PCR to evaluate how well the drug is working.
Chemotherapy
Chemotherapy is the use of drugs to kill cancer cells. In systemic chemotherapy, the drugs travel through the bloodstream to cancer cells throughout the body.
Because chemotherapy affects normal cells as well as cancer cells, many people experience side effects from treatment. Side effects depend on the specific drug and the dosage. Common side effects include nausea and vomiting, loss of appetite, diarrhea, fatigue, low blood count, bleeding or bruising after minor cuts or injuries, numbness and tingling in the hands or feet, headaches, hair loss, and darkening of the skin and fingernails. Side effects usually go away when treatment is complete.
A drug called hydroxyurea (Hydrea) is often given initially to reduce the white blood cell count until the definite diagnosis of CML is made with the tests described above. Given orally (in pill form), the drug is effective at normalizing the blood counts and reducing the size of the spleen, but it does not eliminate the cells with the Philadelphia chromosome and does not prevent the onset of blast crisis. Although hydroxyurea has few side effects and is well tolerated, most newly diagnosed patients in chronic phase are treated with imatinib as soon as possible.
The medications used to treat cancer are continually being evaluated. Talking with your doctor is often the best way to learn about the medications prescribed for you, their purpose, and their potential side effects or interactions with other medications. Learn more about your prescriptions through Cancer.Net's Drug Information Resources, which provides links to searchable drug databases.
Stem cell transplantation/bone marrow transplantation
A stem cell transplant is a medical procedure in which diseased bone marrow is replaced by highly specialized cells, called hematopoietic stem cells. Hematopoietic stem cells are found both in the bloodstream and in the bone marrow. Today, this procedure is more commonly called a stem cell transplant, rather than bone marrow transplant, because blood stem cells are typically what is being transplanted, not the actual bone marrow tissue.
There are two types of stem cell transplantation depending on the source of the replacement blood stem cells: allogeneic (ALLO) and autologous (AUTO). Only ALLO transplants are used in the treatment of CML.
In an ALLO transplant, stem cells are obtained from a donor whose tissue matches the patient’s on a genetic level; this testing is called HLA-typing. Most often, a patient’s brother or sister serves as the donor, although unrelated donors can serve as the donor too. Millions of people worldwide have volunteered to donate stem cells for patients who do not have matched family members; matches can be made by searching a computer registry. In addition, stem cells derived from umbilical cord blood are sometimes considered if family donors are not available.
In an AUTO transplant, the patient’s own stem cells are used. The stem cells are obtained from the patient when he or she is in remission from previous treatment. The stem cells are then frozen until they are needed, usually after the high-dose treatment (explained below) is completed. However, AUTO transplants are not used for patients with CML.
In both types, the goal of transplantation is to destroy cancer cells in the marrow, blood, and other parts of the body and have replacement blood stem cells create healthy bone marrow. In most stem cell transplants, the patient is treated with high doses of chemotherapy and/or radiation therapy to destroy as many cancer cells as possible. This also destroys the patient’s bone marrow tissue and suppresses the patient’s immune system so that, in an ALLO transplant, the donor cells are not rejected by the body. After the high-dose treatment is given, blood stem cells are infused into the patient’s vein to replace the bone marrow and restore normal blood counts from donor cells. Sometimes, ALLO transplants can also be performed after giving lower doses of chemotherapy and/or radiation therapy that are still sufficient to suppress the immune system and allow growth of the donor cells. (These transplants, sometimes termed “mini-transplants” or “reduced intensity transplants” have less immediate side effects, allowing the procedure to be used for older patients.)
Before recommending transplantation, doctors will talk with the patient about the risks of this treatment and consider several other factors, such as the type of cancer, results of any previous treatment, and patient’s age and general health.
For both ALLO and AUTO transplant types, the replacement cells engraft (begin to make new blood cells) and turn into healthy, blood-producing tissue in 10 days to three weeks. Destroying the patient’s own marrow reduces the body’s natural defenses, temporarily leaving the patient at an increased risk of infection. Until the patient’s immune system is back to normal, patients may need antibiotics and blood transfusions.
In an ALLO transplant, another major risk is that the donor’s cells will recognize the patient’s body as foreign, causing graft-versus-host disease (GVHD). GVHD may be a serious complication of allogeneic transplants and can be fatal. Other side effects may include liver problems, diarrhea, infections, and rashes. However, GVHD can also be a benefit, in that the donor cells can recognize the cancer cells as foreign and destroy these cells, a mechanism that is one of the major reasons why ALLO transplantation generally works so well over the long term. The risk of GVHD can be reduced with exact HLA-type matching and the use of preventative drugs.
Learn more by reading the Cancer.Net Feature series, Understanding Bone Marrow and Stem Cell Transplantation.
Although transplantation can successfully cure CML, unsuccessful ALLO transplantations can actually shorten a patient’s life compared with less intensive treatments.
Imatinib has been so effective in suppressing CML cells that transplantation is now generally recommended only for patients whose cancer does not respond to imatinib, recurs (comes back after treatment), or worsens while being treated with imatinib. If imatinib treatment doesn’t work, the decision to undergo transplantation versus treatment with nilotinib or dasatinib can be complex and difficult, and patients are strongly encouraged to seek the advice of doctors experienced in the treatment of CML.
Interferon
Interferon is a type of immunotherapy (also called biologic therapy) designed to boost the body's natural defenses to fight the cancer. It uses materials made either by the body or in a laboratory to bolster, target, or restore immune system function. Interferon can reduce the white blood cell count and sometimes decrease the number of cells that have the Philadelphia chromosome. It is given by daily injections under the skin and causes flu-like side effects, such as fever, chills, and loss of appetite.
When given on an ongoing basis, it can cause fatigue, loss of energy, and memory changes. Interferon therapy was the primary treatment for chronic phase CML before imatinib became available. A clinical trial showed that imatinib was more effective than interferon, producing much higher success rates with fewer side effects. Therefore, interferon is no longer recommended as initial treatment for CML.
Treatment by phase
Chronic phase
The immediate goals of treatment are to alleviate any symptoms the patient may be experiencing with the longer-term goal of decreasing or eliminating the cells with the Philadelphia chromosome to delay or prevent the progression of the disease to blast crisis. Treatment may include one or more of the drugs mentioned above or ALLO transplantation.
Accelerated phase
The same drugs used in chronic phase CML may also be used in the accelerated phase. Although treatment with imatinib can be successful during this stage, the response rate is much lower than in chronic phase, and most patients have a recurrence within about two years. Therefore, an ALLO transplant should be considered when possible. If an ALLO transplant is not recommended or if a matched donor cannot be identified, the treatment plan may include dasatinib, nilotinib, or experimental treatments being tested in clinical trials.
Blastic phase
Treatment with imatinib produces only short periods of response that last a few months in a small number of patients in blast crisis, but it can help to control the CML while transplantation is being arranged. Transplantation is less successful than in chronic phase, but some patients have been successfully treated with this approach. Many people with CML in blastic phase are treated with chemotherapy usually used for patients with acute myeloid leukemia (AML). The chance of remission from this approach is about 20%; most patients’ leukemia recurs within weeks to a few months. Hydroxyurea is frequently given to patients because it can help control blood counts. If transplantation is not an option, the doctor may recommend experimental treatments being tested in clinical trials.
To learn about the terms used in this section, read the Cancer.Net Feature: Cancer Terms to Know: During Treatment.
Printer-Friendly
E-mail this page