All About Chronic Myeloid Leukemia (CML)

This article is a more specific discussion of CML. Please be sure to read All About Leukemia first, so you have an understanding of leukemia. 

What is CML?

CML is a chronic form of leukemia, which is a blood cancer. CML stands for “Chronic myeloid leukemia” or “chronic myelogenous leukemia.” 

• Chronic means the cancer progresses slowly. 
• Myeloid or myelogenous is the term used for blood cells that grow into either: 
  • Red blood cells.
  • Platelets.
  • Granulocytes: In CML, too many blood cells become granulocytes. These granulocytes are not healthy cells. 
  • Leukemia is the term used for too many granulocytes in the blood. The leukemia cells build up in your blood and bone marrow, leaving little room for healthy cells.

CML starts with a problem in two chromosomes that leads to this overgrowth of white blood cells. The cells that make up the human body each contain 23 pairs of chromosomes, which make up your DNA. CML happens when DNA from chromosome 9 is found on chromosome 22 and vice versa. This causes chromosome 22 to be shorter, which is abnormal. This abnormal chromosome is called the Philadelphia chromosome and is found on the leukemia cells of almost all people who have CML. The movement of DNA from one chromosome to another makes a new gene, an oncogene, called BCR-ABL. It now makes the BCR-ABL protein, tyrosine kinase, which makes the cancer cells grow out of control. 

What causes CML and am I at risk?

In most cases, the cause of CML is not known. Although a genetic mutation (BCR-ABL rearrangement) has been identified, it is not clear what causes this mutation. Exposure to high doses of radiation (such as those after an atomic bomb or older radiation treatment methods for cancer) raises the risk of getting the disease. Chemical exposure has not been shown to cause CML, nor is there a hereditary link. Although the BCR-ABL gene is sometimes found in other leukemias, in a person with clinical signs of CML, the finding of the BCR-ABL gene rearrangement confirms the diagnosis.

CML makes up about 15% of all leukemia cases. There are about 9,110 new cases diagnosed each year. The average age at diagnosis is 64. It is more common in men than women.

How can I prevent CML?

Because we don’t know the cause of the gene mutation that leads to CML, there aren’t any ways to prevent CML from developing. It is also important to exercise, avoid smoking, and maintain a healthy diet to lower your risk of cancer in general.

What screening tests are used for CML?

There are no standard screening tests recommended for CML.

What are the signs of CML?

The signs and symptoms of CML are not specific to the disease. The most common symptoms are a result of abnormal blood counts and include:

• An enlarged spleen (splenomegaly). This tends to be present in the blast phase (detailed below). This causes abdominal (belly) fullness, discomfort, and feeling full early when eating (the spleen presses on the stomach).
• Fatigue.
• Shortness of breath.
• Infection.
• Bruising.
• Bleeding.
• Weight loss. 
• Bone pain. 
• Fever.
• Night sweats.

How is CML diagnosed? 

If your provider thinks you have CML, the first step will likely be to have blood work. A blood test called a complete blood count (CBC) will be done to check the levels of red blood cells, white blood cells, and platelets. A test called a smear may also be done to look at your blood cells with a microscope. Gene testing will also be done to look for the Philadelphia chromosome. Along with blood tests, you will likely have a bone marrow biopsy done. Imaging tests, such as a CT scan, may be done to see if the leukemia has spread to any organs in your body. 

How is CML staged?

CML is not staged like other cancers. It is broken down into three phases. The phases are identified by the number of immature white blood cells (called blasts) that are present in the bloodstream. This is also a sign of how aggressive the disease is at that point:

• Chronic: Defined as less than 10% blast cells in the blood and is the least aggressive of the phases.
• Accelerated: Defined as having between 10-19% blast cells in the blood. 
• Blast: Defined as 20% or more blast cells seen in the blood and is the most aggressive phase of the disease.

How is CML treated?

Tyrosine kinase inhibitors (TKI) are the standard treatment for CML. Tyrosine kinase is a type of protein called an enzyme. The Philadelphia chromosome/bcr-abl gene associated with CML produces tyrosine kinase. TKIs block the function of tyrosine kinase. These medications can also cause the bcr-abl expressing genes to die, which is known as apoptosis. 

TKI’s used in the treatment of CML include imatinib, dasatinib, nilotinib, bosutinib and ponatinib. These medications are taken for as long as the disease responds to them and as long as side effects are well managed. In many patients, the Philadelphia chromosome becomes undetectable by current testing methods, but studies have shown that the abnormality will return quickly if the medication is stopped. It is important to understand that these medications do not cure CML, but when working, keep the disease from progressing. 

Before the discovery of TKIs, patients with CML were often offered allogeneic stem cell transplant (stem cells from another person), which remains the only way to cure CML. However, transplants do not always put a patient into remission and they also can cause serious side effects, such as graft vs. host disease (GVHD). Transplant is reserved for patients who no longer are responding to TKI medication in the first chronic phase of the disease or as a salvage treatment for advanced disease. It is suggested that at the time of diagnosis of CML, a patient should undergo a "work-up" for allogeneic stem cell transplant including HLA typing, a transplant risk assessment, and evaluation of the likelihood of finding a donor. This will shorten the time needed to prepare for a stem cell transplant if it is decided to be the chosen course of treatment.

Other Treatments

Other types of treatments may be used in cases where TKIs are no longer working to manage the disease. These include omacetaxine mepesuccinate, interferon alfa, chemotherapy, and radiation. A splenectomy (removal of the spleen) may be used in cases where the spleen has become so enlarged that it is pressing against other organs or to manage blood counts.  This does not treat the CML itself.

Omacetaxine mepesuccinate (Synribo™) is a synthetic form of hommoharringtonine, a compound purified from a Chinese evergreen tree, has been approved for the treatment of CML that has not responded to 2 or more TKIs. This medication has been studied specifically in patients with T315I mutations and may be an option for those patients. 

Interferon alfa was also commonly used before imatinib. This therapy may be used in patients who are not able to undergo transplant. 

Chemotherapy may be used in cases where TKIs are no longer working or as part of a stem cell transplant. The chemotherapy you receive will be determined by your care team.  

Radiation may be used to treat organs that are causing symptoms, such as an enlarged spleen pressing against other organs. It can also be used to treat bone pain in cases where the leukemia has led to bone damage. It may also be used in preparation for a stem cell transplant. 

CML can progress, or speed up, and starts to act like an acute form of leukemia. This may also be referred to as "blast phase" or "blast crisis.” Patients may be treated with imatinib or other TKI, chemotherapy drugs similar to those used in AML, or transplant. The treatment chosen will depend on if you have had treatment in the past. 

Clinical Trials

There are clinical research trials for most types of cancer, and every stage of the disease. Clinical trials are designed to determine the value of specific treatments. Trials are often designed to treat a certain stage of cancer, either as the first form of treatment offered or as an option for treatment after other treatments have failed to work. They can be used to evaluate medications or treatments to prevent cancer, detect it earlier, or help manage side effects. Clinical trials are extremely important in furthering our knowledge of the disease. It is through clinical trials that we know what we do today, and many exciting new therapies are currently being tested. Talk to your provider about participating in clinical trials in your area. You can also explore currently open clinical trials using the OncoLink Clinical Trials Matching Service.

Follow Up Care and Survivorship

Patients being treated for CML are followed very closely by their care providers. You will have labs drawn often to monitor their blood counts and to determine if your TKI treatment is continuing to work. In some cases, if the disease has been responsive to a TKI for a few years, you may be able to stop taking the medication. Your labs will be monitored and if need be you can return to taking the medication. If you have had a transplant you will be monitored closely to see if you are in remission, or if you have relapsed. It is important to let your team know right away if you have any new symptoms or are unable to take your TKI medication. 

Relationship challenges, the financial impact of cancer treatment, employment issues, and coping strategies are common emotional and practical issues experienced by CML survivors. Your healthcare team can identify resources for support and management of these practical and emotional challenges faced during and after cancer.

Cancer survivorship is a relatively new focus of oncology care. With nearly 17 million cancer survivors in the US alone, there is a need to help patients transition from active treatment to survivorship. What happens next, how do you get back to normal, what should you know and do to live healthy going forward? A survivorship care plan can be a first step in educating yourself about navigating life after cancer and helping you communicate knowledgeably with your healthcare providers. Create a survivorship care plan today on OncoLink.