Chronic myelogenous leukemia (CML) is a slow-growing bone marrow cancer resulting in too many white blood cells. The disease is also sometimes called chronic myeloid, chronic granulocytic or chronic myelocytic leukemia. CML is a relatively common form of leukemia, but overall it is a relatively uncommon type of cancer. In the United States, more than 20,000 people have CML and about 4,600 new cases are diagnosed each year. Most cases of CML appear in adults, but about 2-4% of CML patients are children.
CML is caused by a change in the genetic code of some of the cells in the bone marrow. In these cells, part of chromosome 9 switches places with a part of chromosome 22, a process called chromosomal translocation. This creates an abnormal chromosome called the Philadelphia chromosome. The rearranged Philadelphia chromosome signals the marrow to overproduce white blood cells. Doctors do not know what causes the Philadelphia chromosome to appear.
Chronic myelogenous leukemia phases and symptoms
CML has three phases. Most patients are diagnosed in the first phase, called the chronic phase. It can develop over time into the second (accelerated) and third (blast) phase. Most, but not all patients are diagnosed in the chronic phase.
In the chronic phase, there are more white blood cells in the blood and bone marrow than usual. Most are mature cells that work normally. In the past, the chronic phase lasted two to five years or more before turning into the accelerated phase. This has changed dramatically since the development of imatinib mesylate (trade name: Gleevec). More than 80% of CML patients now treated with imatinib are stable (getting neither better or worse) at five years.
The symptoms of chronic phase CML can depend on how high the person's white blood cell count is. Often, people do not notice any symptoms at all. Their CML is found during a routine doctor's visit. Others may have symptoms such as:
- Fatigue (tiredness)
- Pain or a feeling of fullness on the left side of the abdomen (caused by an enlarged spleen)
In the accelerated phase, there are increased numbers of immature white blood cells called blast cells in the marrow, blood, liver, and spleen. These blasts cannot fight infections the way normal white blood cells do. In the past, this phase lasted between 1-6 months before progressing to the blast phase. But depending on what drug treatments a CML patient receives, this phase may sometimes last more than a year. Symptoms are more noticeable than in chronic phase. In addition to the chronic phase symptoms above, symptoms in the accelerated phase can include:
- Night sweats
- Weight loss
- Shortness of breath and pale skin caused by anemia (too few red blood cells)
In the blast phase, the number of blasts in the bloodstream grow rapidly. As a result, there are fewer normal blood cells (white blood cells, red blood cells and platelets), and the symptoms listed above become severe. Patients often have problems with bruises, bleeding and infection. When CML is in the blast phase, the disease resembles acute myelogenous leukemia, or in a minority of cases, acute lymphocytic leukemia.
Chronic myelogenous leukemia treatments
Treatment options for CML include:
- Drugs similar to imatinib: dasatinib (Sprycel®) and nilotinib (Tasigna®)
- A marrow, blood stem cell or cord blood transplant
- Interferon, often along with cytarabine
The choice of treatments is based on a patient's age, overall health and related factors. [1, 2] The anti-cancer drugs interferon, cytarabine, and hydroxyurea were the main CML treatments before imatinib became available in 2001, but are now infrequently used.
Imatinib is now usually given to CML patients as a first treatment. If imatinib is ineffective, or if it loses its effectiveness, then two other drugs similar to imatinib are usually used: dasatinib and nilotinib. If these drugs don't work, then a marrow, blood stem cell or cord blood transplant is considered. The major goal of any treatment for CML is the elimination of all cells with the Philadelphia chromosome.
Drug therapies: imatinib, dasatinib, nilotinib
For most CML patients, imatinib is the standard first treatment. Imatinib works by blocking an enzyme in marrow cells so that the body stops (or slows down) making too many white blood cells. 
Most CML patients respond to imatinib. Because it is a relatively new treatment, doctors still have questions about whether patients' response to imatinib will last for a long time. To learn more, see Gleevec Treatment for CML.
In some CML patients taking imatinib, the drug will not be effective, or will work for a while and then lose its effectiveness. One study found that about 30% of patients with newly diagnosed chronic phase CML treated with imatinib didn't achieve complete remission (no sign of the Philadelphia chromosome) after receiving the drug for one year.  In these cases, the typical approach is to try dasatinib or nilotinib, drugs similar to imatinib but having slightly different ways of blocking the enzyme causing the growth of too many white blood cells.  All three drugs work best when given during the chronic phase of CML; they are less effective in the accelerated and blast phases. [1, 4]
Bone marrow or cord blood transplant
A bone marrow or cord blood transplant (also called a BMT) using stem cells from a related or unrelated donor is the only known treatment that can bring a long-term remission from CML. These types of transplants are called allogeneic transplants. Another type of transplant, called an autologous transplant, uses a patient's own cells. Autologous transplants are rarely used to treat CML.
Allogeneic transplantation has risks and is not an option for all patients. A transplant replaces the abnormal stem cells in the patient's bone marrow with healthy stem cells from a donor. The donor's cells also replace the patient's immune system, which can prevent the growth of any remaining CML cells. For details about the transplant process, see Learning about Bone Marrow or Cord Blood Transplants.
However, a transplant is not an option for all patients. Some patients are not strong or healthy enough to tolerate the high doses of chemotherapy and/or radiation used before a transplant. A newer approach, called a reduced-intensity transplant may be an option for some of these patients, as well as for older patients. In addition, some patients do not have a suitable donor to use for transplant.
Even for CML patients in otherwise good health, a transplant has risks of life-threatening complications. If transplant is an option for you, your doctor can talk with you about your risks and your chances of remaining disease-free with transplant. In general, results of a transplant are better if performed in chronic phase. The more advanced the disease, the worse the results. For statistics on transplant outcomes, see CML transplant survival outcomes.
Making treatment choices
For patients with CML in chronic phase, there are better treatment options today than in the past. Even so, research continues to answer questions about the best treatment.
Imatinib helps most CML patients, is generally well-tolerated, and has the longest track record. For these reasons, it is often the standard first treatment for many CML patients. However, it is too soon to know how well it will work over the long term. A transplant may cure CML, but it has serious risks. It is not an option for all patients.
The best treatment will be different for different patients, depending on characteristics of the disease but also on a patient's age and other health factors, including response to imatinib. Research into treatment for CML is ongoing, and recommended treatments continue to change quickly. It is important to talk with your doctor about your treatment options. For a general guide, see Discussing Options with Your Doctor. For specific information about imatinib, see Gleevec Treatment for CML.
Even if you begin treatment with imatinib, it may be a good idea to consider the possibility of a future transplant, if you would otherwise be eligible. Your doctor can then take steps to be prepared if imatinib does not give you good results or if it stops working over time. An important study in 2008 showed that CML patients taking imatinib before a transplant did as well as, or in some cases better than, CML patients who did not take imatinib before transplant.  In other words, a "drug-before-transplant" strategy will likely not affect the outcome of a transplant, should a transplant become necessary.
While you take imatinib or another CML drug, your doctor can still prepare for a possible transplant by checking whether you have any possible donors in your family. He or she can also work with the National Marrow Donor Program® to search for potential unrelated donors or cord blood units on our Be The Match Registry® and other registries. That way, if you and your doctor decide you need a transplant later, the important first steps of the donor search will be done and you may be able to undergo your transplant sooner.
Information to share with your doctor
The Physician section of this website includes information for doctors about timing and outcomes of transplants for CML, as well as references to related medical journal articles. You may want to share some of this information with your doctor.
- Goldman JM. How I treat chronic myeloid leukemia in the imatinib era. Blood. 2007; 110(8):2828-2837.
- Maziarz RT. Who to transplant with CML in the era of tyrosine kinase inhibitors? Curr Opin Hematol. 2008; 15(2):127-133.
- Deininger M, Buchdunger E, Druker BJ. The development of imatinib as a therapeutic agent for chronic myeloid leukemia. Blood. 2005; 105(7):2640-2653.
- O'Brien SG, Guilhot F, Larson RA, et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2003; 348(11):994-1004.
- National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Chronic Myelogenous Leukemia. v.2.2009. http://www.nccn.org/professionals/physician_gls/PDF/cml.pdf
- Lee SJ, Kukreja M, Wang T, et al. Impact of prior imatinib mesylate on the outcome of hematopoietic cell transplantation for chronic myeloid leukemia. Blood. 2008; 112(8):3500-3507.
Marcos de Lima, M.D., University of Texas M.D. Anderson Cancer Center, Houston, Texas
Richard T. Maziarz, M.D., Oregon Health and Science University, Portland, Ore.
Willis Navarro, M.D., National Marrow Donor Program, Minneapolis, Minn.