All About Chronic Myeloid Leukemia (CML)

Autor: Carolyn Vachani, RN, MSN, AOCN
Updated by: Karen Arnold-Korzeniowski, BSN, RN
Contribuidor de contenido: OncoLink Team
Última Vez Revisión: 18 de septiembre de 2019

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 blood cancer, specifically a leukemia. It starts with a defect in two chromosomes that results in an overgrowth of white blood cells. The cells that make up the human body each contain 23 pairs of chromosomes, which makes up your DNA. CML occurs 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 forms 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. 

CML accounts for about 15% of all leukemia cases. There are about 8,990 new cases diagnosed each year. The average age at diagnosis is 64. It is more common in men than women.

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 for 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.

How can I prevent CML?

In most CML cases, we don’t know the cause of the diagnosis. Thus, there aren’t any ways to prevent CML from developing. It is also important to exercise, to avoid smoking, and to maintain a nutritious 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 an enlarged spleen (splenomegaly). Abnormal blood counts can cause fatigue, shortness of breath, infection, bruising and bleeding. Splenomegaly, which tends to be present in the blast phase (detailed below), causes abdominal fullness or discomfort, feeling full early when eating (the spleen is pressing on the stomach), and weight loss. Bone pain, fever, and night sweats are other symptoms that you may experience. 

How is CML diagnosed? 

If your provider suspects you have CML, the first step will likely be to have blood work done. 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: chronic, accelerated, and blast. The phases are identified by the number of immature white blood cells (called blasts) that are present in the blood stream. This is also a sign of how aggressive the disease is at that point. 

  • Chronic phase is defined as less than 10% blast cells in the blood and is the least aggressive of the phases.
  • Accelerated phase is defined as having between 10-19% blast cells in the blood. 
  • Blast phase is 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. 

These medications 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 Treaments

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. But, 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 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. They have labs drawn often to monitor their blood counts and to determine if their 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 some 15 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.

Referencias

Abeloff, M., Armitage, J., Niederhuber, J., Kastan, M. & McKenna, G. (Eds.): Clinical Oncology (2004).Elsevier, Philadelphia, PA.

The American Cancer Society. Chronic Myeloid Leukemia

Apperley, JF. Chronic myeloid leukaemia. Lancet. Dec 5 2014: 385: 1447-59.

Be The Match. Chronic Myeloid Leukemia(CML). 2017.  

Chronic Myeloid Leukaemia:ESMO Clinical Practice Guidelines. 2017. 

Cortes JE, Jones D, O'Brien S, Jabbour E, Ravandi F, Koller C, et al. Results of dasatinib therapy in patients with early chronic-phase chronic myeloid leukemia. J Clin Oncol. Jan 20 2010;28(3):398-404.

Druker BJ, Sawyers CL, Kantarjian H, et al. Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N Engl J Med. Apr 5 2001;344(14):1038-42

Gratwohl A, Baldomero H, Passweg, J. The role of hematopoietic stem cell transplantation in chronic myeloid leukemia. Annals of Hematology. 2015; 94(2): 177-186.

Kantarjian, H et al. Homoharringtonine/Omacetaxine: The Little Drug that Could. The ASCO Post, Vol 4, Issue 6, April 15, 2013.

Leukemia and Lymphoma Society – Chronic Myeloid Leukemia

NCCN Practice Guidelines in Oncology. Chronic Myeloid Leukemia. Version 1.2020. 

Shah NPKim DWKantarjian H, et al. Potent, transient inhibition of BCR-ABL with dasatinib 100 mg daily achieves rapid and durable cytogenetic responses and high transformation-free survival rates in chronic phase chronic myeloid leukemia patients with resistance, suboptimal response or intolerance to imatinib. Haematologica.2010;95(2):232-40

Simonsson B, Gedde-Dahl T, Markevarn B, et al. Combination of pegylated IFN-a2b with imatinib increases molecular response rates in patients with low- or intermediate-risk chronic myeloid leukemia. Blood. 2011;118(12):3228-35.

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