Chronic Phase
If you have chronic myeloid leukemia (CML), you very likely will have no symptoms. You may not realize you have a serious disease unless a routine blood test shows a high white blood cell count. CML is very well controlled with Gleevec® (imatinib mesylate). Survival rate at 5 years is more than 90 percent.
If this fails, doctors often use a procedure called allogeneic stem cell transplant. Stem cells are taken from a compatible donor and injected into the patient. This replaces the stem cells that are destroyed by chemotherapy and allows the patient to resume making blood cells. Allogeneic stem cell transplantation makes it possible to rid the patient of abnormal cells. Many patients are cured with this treatment.
Imatinib mesylate has been approved for the treatment of CML. Imatinib mesylate controls the faulty chemical messages that the Philadelphia chromosome produces. It causes few side effects and appears to produce long-term remissions. All other current therapies are aimed at controlling the growth of abnormal cells and attempting to delay the progression from the chronic phase to the more serious blastic phase.
When deciding whether to get treatment for CML, you should be aware of the goals of your therapy. Treatment may be given to prolong survival, to increase the chance of a cure, or to improve symptoms. You and your doctor should carefully balance the potential benefits of receiving cancer treatment with the potential risks.
The following is a general overview of the treatment of CML in the chronic phase. Your individual situation may influence your decision to have treatment and what type it should be. The potential benefits of receiving treatment must be carefully balanced with the potential risks. The information on this website is intended to help educate you about your treatment options. It can help you when you make decisions with the cancer specialist who treats you.
Most new treatments are developed in clinical trials. These are studies that evaluate the safety and effectiveness of new drugs or treatments. Clinical trials make it possible to develop more effective cancer treatments. If you take part in a clinical trial, you may get better treatments. You will also help to advance our knowledge about treatment of CML.
Clinical trials are available for most stages of cancer. If you are interested in participating in a clinical trial, you should discuss with your physician the risks and benefits of taking part. In any case, you should stay informed by following the news about CML trials. In this way, you can make sure that you are receiving the best treatment available.
You may face some difficult decisions about your treatment for CML. Allogeneic stem cell transplants can cure most patients in the chronic phase if used within approximately 1 to 2 years of diagnosis. The side effects can be very serious, however, and between 10 percent and 40 percent of patients die of complications from treatment. Also, the chances that your allogeneic transplant will be successful decrease the longer you wait to receive treatment.
Treatment of Chronic Phase CML with Imatinib Mesylate
Most CML cases are caused by the Philadelphia chromosome. This faulty chromosome produces a protein called the Bcr-Abl tyrosine kinase. The Bcr-Abl tyrosine kinase protein stimulates cells to grow and reproduce in an uncontrolled manner.
Imatinib Mesylate
This is a tyrosine kinase inhibitor that attaches to the Bcr-Abl tyrosine kinase and blocks the growth effects caused by Bcr-Abl. This, in turn, halts the excessive replication and growth of cancer cells. Since imatinib mesylate only binds to cancer cells, side effects are minimal. Imatinib mesylate is now standard first-line therapy in CML.
Nilotinib
Patients who have chronic or accelerated phase CML that is resistant or intolerant to imatinib may benefit from this new drug that was recently approved for CML.
Dasatinib
This treatment is indicated for adults with chronic, accelerated, or myeloid or lymphoid blast phase chronic myeloid leukemia (CML) that is resistant or there is intolerance to prior therapies, including imatinib.
Hydroxyurea
Hydroxyurea is an oral chemotherapy drug given to control the white blood cell count and to treat or prevent an enlarged spleen. This drug has few side effects. It does not destroy bone marrow stem cells. It is effective in reducing the white blood cell and platelet levels.
Hydroxyurea is the drug of choice for controlling the first signs of CML in the chronic phase because of its relative freedom from side effects. Hydroxyurea is also used in patients who cannot tolerate or choose not to be treated with imatinib mesylate. However, hydroxyurea is only a temporary measure and should not be used alone as long-term treatment of CML.
Alpha Interferon
Interferon is a biologic agent, which means that it works by helping the body's natural defense system fight the growth of cancer cells. Interferon is more effective than hydroxyurea. However, the high doses of interferon needed to control the disease cause side effects that may affect the quality of life of some patients.
Stem Cell Transplantation
A stem cell transplant is a procedure that is performed to repair the damage caused by high-dose chemotherapy (HDC). HDC kills more cancer cells than lower-dose conventional chemotherapy. Unfortunately, HDC also kills more normal cells, especially the blood-producing stem cells in the bone marrow. Stem cells are immature cells produced in the bone marrow. They develop into red blood cells, which provide oxygen to tissue; white blood cells, which fight infection; or platelets, which aid in blood clotting.
Stem cell transplant is intended to restore the blood-producing stem cells after HDC has reduced them to dangerously low levels. When stem cells reach critically low levels from HDC, complications—such as anemia, infection, and bleeding—can occur. Thus, it is essential to restore stem cell levels as quickly as possible.
An allogeneic stem cell transplant uses stem cells collected from a related or unrelated donor. An autologous stem cell transplant involves the collection of a patient's own stem cells before chemotherapy treatment. These stem cells are frozen and then infused back into the patient after treatment to "rescue" the bone marrow. Autologous stem cell transplant is investigational in CML; its value is not proven.
Allogeneic Stem Cell Transplant
An allogeneic stem cell transplant for treatment of newly diagnosed patients with CML in the chronic phase can result in improved long-term survival. Unfortunately, this procedure also carries a significant risk of serious side effects, including death. One-third of patients will have a compatible family stem cell donor and up to 70 percent of the population will have a suitable unrelated donor. When age and donor availability are taken into consideration, most patients are unable to choose this treatment.
Given the wide range of reported outcomes, you should ask about the mortality rates for this procedure at your treating center before making a decision. In general, it is stem cell transplant is considered only after failure of imatinib therapy.
Some doctors may still recommend early allogeneic stem cell transplantation as the treatment of choice for patients under age 60 with suitable family donors and those under age 45 with an HLA-matched unrelated donor. Patients transplanted in the chronic phase in some transplant centers have a 10 percent chance of dying from the treatment in the first year and a 5-year survival rate of 80 percent.
Research is in progress to refine existing treatments and develop new ones. For information on some of the techniques currently under investigation, see Strategies to Improve Treatment.
This content was last reviewed
August 15, 2010 by Dr. Reshma L. Mahtani.