How Is Chronic Myeloid Leukemia Treated?
Treatment options and recommendations for people with chronic myeloid leukemia depend on several factors, including the phase of the disease, possible side effects, and your preferences and overall health. Take time to learn about your treatment options, and be sure to ask questions about things that are unclear. Also, discuss the goals of each treatment with your doctor and ask what you can expect while receiving the treatment.
Targeted therapy is a treatment that attacks the cancer’s specific genes, proteins, or the tissue environment that contributes to cancer growth and survival. This type of treatment blocks the growth and spread of cancer cells while limiting damage to normal cells.
Not all cancers have the same targets. To find the most effective treatment, your doctor may run tests to identify the genes, proteins, and other factors involved in your leukemia. As a result, doctors can better match each individual with the most effective treatment whenever possible.
For CML, the target is the unique protein called the BCR-ABL tyrosine kinase enzyme. There are five drugs, called tyrosine kinase inhibitors or TKIs, currently used to target tyrosine kinase enzymes for CML: imatinib (Gleevec), dasatinib (Sprycel), nilotinib (Tasigna), bosutinib (Bosulif), and ponatinib (Iclusig). All five drugs can stop the BCR-ABL enzyme from working, which causes the CML cells to die quickly.
To find the most effective treatment, your doctor may run tests to identify the genes, proteins, and other factors involved in your leukemia.
People receiving a TKI should have regular check-ups to see how well the treatment is working. Sometimes, a tyrosine kinase drug stops working and the CML develops resistance to it. Resistance can occur if a person does not take his or her medication regularly, as prescribed. Even if the medication is taken correctly, CML may become resistant to TKIs, so it’s important to receive regular monitoring with cytogenetic testing, fluorescence in situ hybridization (FISH) testing, or polymerase chain reaction (PCR) testing to determine how well the drug is continuing to work. If the medication you start with stops working, the dose may be increased or a different tyrosine kinase drug may still be effective.
This type of treatment is the use of drugs to kill cancer cells, usually by stopping the cancer cells’ ability to grow and divide. In systemic chemotherapy, the drugs travel through the bloodstream to reach cancer cells throughout the body. A chemotherapy regimen usually consists of a specific number of cycles given over a set period. You may receive one drug at a time or combinations of different drugs at the same time.
Treating CML by Phase
Chronic Phase The immediate goals of treatment are to reduce any symptoms you may have. The longer-term goals are to decrease or get rid of the cells with the Philadelphia chromosome in order to slow down or prevent the disease from moving to blast crisis. Treatment will often first include use of a tyrosine kinase inhibitor. An allogeneic stem cell transplantation would be considered afterward only if the TKI treatment is not successful.
Accelerated Phase The same drugs used for chronic phase CML may also be used in the accelerated phase. Although treatment with a TKI can work well during this stage, it is less likely to work as well as it does for chronic phase CML, and many people have a recurrence within about two years. Dasatinib or nilotinib are more effective in providing longer remissions. Therefore, an allogeneic stem cell transplantation should be considered when possible. If an allogeneic stem cell transplantation is not recommended or if a matched donor cannot be found, the treatment plan may include a different TKI or a clinical trial.
Blastic Phase Treatment with a TKI only works well for a few months for people in blast crisis, but it can help to control the CML while a stem cell transplant is being arranged. If the transplant can be done while imatinib or dasatinib is working, then the long-term results are better. Stem cell transplantation in the blast phase is less successful than in chronic phase, but this approach has worked well for some. Many people with CML in blastic phase receive imatinib or dasatinib plus chemotherapy similar to that used for people with acute myeloid leukemia. The chance of remission from this approach is about 20 to 30 percent, although the leukemia recurs for most people within weeks to a few months. Hydroxyurea is often given because it can help control blood cell levels. If stem cell transplantation is not an option, your doctor may recommend a clinical trial.
A drug called hydroxyurea (Hydrea, Droxia) is often given to lower the number of white blood cells until the definite diagnosis of CML is made. Given in capsule form, this drug works well to return blood cells to normal levels within a few days or weeks and reduce the size of the spleen, but it does not reduce the percentage of cells with the Philadelphia chromosome and does not prevent blast crisis (when more than 30 percent of the cells in the blood or bone marrow are immature white blood cells) alone. Although hydroxyurea has few side effects, most people newly diagnosed with chronic phase CML receive imatinib or other tyrosine kinase inhibitors as soon as possible.
In 2012, the drug omacetaxine mepesuccinate (Synribo) was approved by the FDA for people with chronic or accelerated phase CML that is not responding to a TKI. Omacetaxine is given by injection under the skin daily for seven to fourteen days.
Stem Cell Transplantation
A stem cell transplant is a medical procedure in which bone marrow that contains leukemia is replaced by highly specialized cells called hematopoietic stem cells that develop into healthy bone marrow. Hematopoietic stem cells are found both in the bloodstream and in the bone marrow. Before recommending transplantation, doctors will talk with you about the risks of this treatment and consider several other factors, such as your type of leukemia, results of any previous treatment, and your age and general health.
There are two types of stem cell transplantation: allogeneic and autologous. A person undergoing an allogeneic transplant receives cells from another person, whereas a person undergoing an autologous transplant receives his or her own stem cells. Only allogeneic transplants are used to treat CML. In both types, the goal of transplantation is to destroy cancer cells in the marrow, blood, and other parts of the body and allow replacement blood stem cells to create healthy bone marrow. In most stem cell transplants, a person receives high doses of chemotherapy, radiation therapy, or both to destroy as many cancer cells as possible.
Also called biologic therapy, immunotherapy is 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 improve, target, or restore immune system function. Interferon (Roferon-A, Intron A, Alferon, Infergen) is a type of immunotherapy. It can reduce the number of white blood cells and sometimes decrease the number of cells that have the Philadelphia chromosome. Interferon therapy was the primary treatment for chronic phase CML before the targeted therapy imatinib became available. A clinical trial showed that imatinib worked better to treat CML than interferon, with fewer side effects. Therefore, interferon is no longer recommended as the first treatment for CML.
In addition to treatment to slow, stop, or eliminate the disease, an important part of care is relieving symptoms and side effects of CML and its treatment. This approach is called palliative or supportive care, and it involves addressing your physical, emotional, and social needs at any stage of illness.
In addition to treatment to slow, stop, or eliminate the disease, an important part of care is relieving symptoms and side effects of CML and its treatment.
Palliative treatments often include medication, nutritional changes, relaxation techniques, and other therapies. You may also receive palliative treatments similar to those meant to eliminate the leukemia, such as chemotherapy, surgery, and radiation therapy.
Before treatment begins, talk with your healthcare team about the possible side effects of your specific treatment plan and your supportive care options. During and after treatment, be sure to speak up if you’re experiencing a problem so it can be addressed as quickly as possible.
It is not yet proven whether imatinib, dasatinib, or nilotinib, or the newer drugs bosutinib, ponatinib, or omacetaxine, can cure CML. A remission (when leukemia cannot be detected in the body by cytogenetic testing and there are no symptoms) can be temporary or permanent. This uncertainty leads to many survivors feeling worried or anxious that the leukemia will come back. While many remissions are permanent, understanding the risk of recurrence and your treatment options may help you feel more prepared if the leukemia does return.
If the leukemia returns despite the original treatment, it’s called recurrent leukemia. When this occurs, you will undergo another cycle of testing to learn as much as possible about the recurrence, including whether the leukemia is in a different phase. After testing is finished, you and your doctor will talk about your treatment options. Often the treatment plan will include therapies such as targeted therapy, chemotherapy, and immunotherapy, but they may be used in a different combination or given at a different dose than the first time you were treated. Your doctor may also suggest clinical trials that are studying new ways to treat your type of recurrent leukemia.
People with recurrent leukemia often experience emotions such as disbelief or fear. If you experience these emotions, you should talk with your healthcare team about your feelings and ask about support services to help you cope.
If the leukemia does not respond to treatment, it is called refractory leukemia. People with this diagnosis are encouraged to talk with doctors who are experienced in treating this type of leukemia, because there can be different opinions about the best treatment plan. You might consider seeking a second opinion before starting treatment so you are comfortable with the treatment plan chosen. Supportive care will be important to help relieve symptoms and side effects.
For most people, a diagnosis of refractory leukemia is very stressful and, at times, difficult to bear. People with refractory leukemia and their families are encouraged to talk about their feelings with doctors, nurses, social workers, or other members of the healthcare team. It may also be helpful to talk with others with the same diagnosis, including through a support group.
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Reprinted with permission from Cancer.Net © 2013 American Society of Clinical Oncology. All rights reserved.
This article was originally published in Coping® with Cancer magazine, November/December 2013.
Coping® does not endorse or recommend any particular treatment protocol for readers, and this article does not necessarily include information on all available treatments. Articles are written to enlighten and motivate readers to discuss the issues with their physicians. Coping believes readers should determine the best treatment protocol based on physicians’ recommendations and their own needs, assessments and desires.