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Chronic Myelogenous Leukemia

Chronic myelogenous leukemia (CML) is a type of cancer that begins in the bone marrow, where all blood cells are formed, and causes the bone marrow to make too many white blood cells. The disease is called “chronic” because it is slow-growing, and “myelogenous” because it affects the myeloid cells, which develop into red blood cells, white blood cells, or platelets. Two additional terms for this disease are chronic myeloid leukemia and chronic granulocytic leukemia.

According to the American Cancer Society, roughly 9,000 people in the United States are diagnosed with CML each year, making it a rare type of cancer. It is most often diagnosed in individuals who are 65 years of age and above. It is also slightly more common in men than in women.

The amount of progress made in the field of CML research within the last several years is astounding, and the 5-year survival rate has improved by more than double since the 1990s. Scientific advances have led to better treatment options and longer life expectancies, giving CML patients and their loved ones many reasons to remain hopeful.

What Is Chronic Myelogenous Leukemia?

Chronic myelogenous leukemia, or CML for short, is a type of cancer that causes the bone marrow to make too many white blood cells. The disease is called “chronic” because it is slow-growing, and “myelogenous” because it affects myeloid cells, a type of white blood cell produced in the bone marrow.

CML is also known as chronic myeloid leukemia and chronic granulocytic leukemia. A granulocyte is a type of white blood cell.

CML Symptoms

CML can be diagnosed without symptoms after discovery of an elevated white blood cell count during a routine blood test. The symptoms of CML often include one or more of the following:

  • weight loss
  • weakness
  • fatigue
  • sweating
  • night sweats
  • pain or feeling of fullness in the stomach
  • enlarged spleen (mass felt to the left of and below the ribcage)
  • unusual bruising or bleeding

Because the disease lowers the number of healthy red blood cells in your body, it creates anemia in some patients, which encapsulates a number of the symptoms listed above. It could also cause an increase in the platelet count.

The symptoms of chronic myelogenous leukemia are similar to those of other types of cancer, as well as many other medical conditions. If you have questions or concerns about your health, please consult with a healthcare professional.

What Causes CML?

CML is caused by the fusion of two genes, BCR located on chromosome 22, and ABL1 located on chromosome 9, leading to an abnormal protein, BCR-ABL1, which drives this disease. BCR-ABL1 is an oncogene (cancer-causing gene) that causes cells to grow and divide at abnormal rates.

This fusion is caused by a translocation, which is the swapping of genetic material between chromosomes 9 and 22. This creates an abnormally short chromosome 22, which has been named the Philadelphia Chromosome.

CML Risk Factors

CML is a rare disease, with less than 9,000 cases diagnosed in the United States annually. As such, there are very few risk factors with a proven link to CML. The known risk factors include:

  • Age: Most people diagnosed with CML are age 65 or older. Risk increases with age.
  • Gender: While the reasons for this are not yet clear, men are more likely than women to develop CML.
  • Radiation: mostly described in catastrophic high-dose radiation such as in survivors of an atomic bomb blast or nuclear reactor accidents.

CML Diagnosis

If you develop CML symptoms, your doctor will likely recommend one or more of these tests to confirm or rule out the disease.

Here is a list of what you might experience.

  • Physical Exam: Your doctor will likely start with a physical exam, which usually includes questions about your family medical history, pre-existing conditions and overall health.
  • Blood tests: Many patients with CML have elevated white blood cell counts. After a physical exam your doctor will likely order a complete blood count (CBC). This test measures the level of red blood cells, white blood cells and platelets in your blood. Additionally, your doctor will likely look at the size and shape of your blood cells under a microscope to determine if they contain indicators of CML.
  • Bone marrow biopsy: There are two parts to this procedure: bone marrow aspiration and biopsy. The procedure itself is an office procedure lasting for 15-20 minutes. A local anesthetic is injected to numb the skin and covering of the bone called the periosteum. During the biopsy procedure, a small amount of bone marrow tissue will be withdrawn with a needle (aspiration) and a marrow core (biopsy) will be taken from the hip bone. This allows doctors to see if your bone marrow contains an abundance of cells that create blood (meaning your bone marrow is hypercellular). This is common in patients with CML.
  • Tests for the BCR-ABL1 fusion gene: several highly specialized tests can analyze your blood or bone marrow for the presence of the Philadelphia chromosome and the BCR-ABL1 fusion gene. The BCR-ABL1 gene is present in all cases of CML and the Philadelphia Chromosome is detected in most cases. Therefore, genetic testing is used to confirm a CML diagnosis.

I’ve Been Diagnosed with Chronic Myelogenous Leukemia, Now What?

Your healthcare provider will help you determine the best immediate course of action. By this time, most patients diagnosed with CML will be under the care of a doctor who specializes in hematology/oncology. If you have not yet consulted a specialist, now is the time to do so. With telemedicine, you may even be able to speak to a leukemia expert from the comfort of your own home.

Some patients find that joining a cancer support group helps them process their diagnosis and learn from others who are on a similar journey.

CML Treatment

There is a range of effective treatment options for CML, but most patients will start with targeted therapy.

Targeted Therapy

This treatment uses drugs that focus on specific abnormalities of cancer cells causing them to die. With CML, the abnormal BCR-ABL1 gene gives targeted therapy drugs known as tyrosine kinase inhibitors (TKIs) something to target by directly blocking the BCR-ABL protein that causes this disease. TKIs used to treat CML include:

  • imatinib (Gleevec)
  • dasatinib (Sprycel)
  • nilotinib (Tasigna)
  • bosutinib (Bosulif)
  • ponatinib (Iclusig)

A major study using imatinib reported the 5-year survival rates of participants at 90%, and most had normal white blood cells and chromosomes after years of using the drug. TKIs are considered to be the most effective treatment option for CML.


Before the invention of TKIs, interferon therapy was the primary treatment for CML. Interferons are naturally made by our immune systems, and in CML treatment a man-made version of these, called interferon-alpha, halts the division and growth of leukemia cells. When used, interferon is most often given as a daily injection under the skin.

Chemotherapy or Radiation

CML could rarely progress to an acute leukemic phase called the blast phase (discussed in the CML Stages" section below), where doctors may use chemotherapy or radiation therapy in addition to TKIs.

Chemotherapy uses strong oral and/or intravenous drugs to attack cells that are in the process of dividing. It primarily kills cancer cells, but some healthy cells will be affected too.

Radiation therapy uses X-rays to target and attack cancer cells. The goal of radiation therapy is to damage the cancer cells and stop them from spreading.

Stem Cell Transplant

In certain cases of resistant CML, doctors may recommend a stem cell transplant. There are two types of stem cell transplants: autologous (using the patient’s own cells) and allogeneic (using cells from a donor). During this process, stem cells, which generate all other specialized cells, are taken from either the bone marrow or the bloodstream. They are frozen and stored while the patient undergoes high doses of chemotherapy, or other intense treatments, and then transplanted back into the patient’s body, where they generate new, healthy cells.

Questions for Your Doctor

Here are a few questions to ask when discussing treatment options with your doctor:

  • What phase is the cancer and what does that mean?
  • Do I need to start treatment right away?
  • Which treatment option(s) do you recommend, and why?
  • How long will the treatment last?
  • What are the risks and side effects?
  • How will we know the treatment is working?

Your treatment plan will depend on your symptoms, overall health and fitness level, results of your blood tests and your own personal preferences. Once treatment begins, your progress will be closely monitored. Talk to your doctor, and to a leukemia specialist, to get the care that’s right for you.

CML Stages

The stages of CML are usually referred to as phases because unlike many other cancers, CML rarely forms tumors. The three phases are differentiated by the blasts, or immature white blood cells, in the bone marrow.

  • Chronic phase: A patient’s blood or bone marrow usually has less than 10% blasts and there are mild symptoms or none at all. Most people who develop CML fall into the chronic stage.
  • Accelerated phase: A patient is considered to be in the accelerated phase when their blood or bone marrow has 15% or more blasts, but fewer than 30%, and when blasts and promyelocytes combined make up 30% or more than the blood. Also, doctors look for very low platelet counts to determine this stage. Patients in this phase generally have poor appetite and experience weight loss as well.
  • Blast phase (or acute phase): This occurs when a patient’s blood is 20% or more blasts, and large groups of blasts are found in the bone marrow. Additionally, in this phase, blast cells have usually spread to other organs and tissue.

CML Survival Rate

Patients enrolled in clinical trials when newly diagnosed with CML have a 5-year survival rate above 90%, meaning that more than 90 of 100 people with CML were still alive five years after their diagnosis. And patients with successful eradication of the Philadelphia chromosome at one year of therapy have a lifespan similar to that of individuals without CML.

According to Surveillance, Epidemiology, and End Results (SEER) data, published by the National Cancer Institute, the relative five-year survival rate from 2010 to 2016 was 70.4%. This discrepancy between clinical trial results and SEER results could be related to selecting patients with fewer concomitant illnesses for clinical trials or to limited access of some patients not enrolled in clinical trials to therapy or to specialized centers, leading to an inferior chance of survival.

Research and clinical trials have dramatically improved CML outcomes in recent years. In the 1970s, the five-year survival rate for CML was 22%. In the 1990s, it was 31%. A primary factor in the improvement of CML survival rates in recent years is the implementation of tyrosine kinase inhibitors (TKIs). Ongoing medical advancements continue to push survival rates even higher.


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