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Chronic Myeloid Leukemia (CML): An Overview

Posted on May 26, 2021
Medically reviewed by
Todd Gersten, M.D.
Article written by
Maureen McNulty

Chronic myeloid leukemia (CML) is a type of blood cancer. CML is chronic, which means that the leukemia cells grow slower than those in acute forms of the condition. As such, they may not cause signs or symptoms for a long time.

CML develops from immature myeloid cells located in the bone marrow (spongy tissue found inside certain bones). Myeloid cells include red blood cells, certain types of white blood cells, and the cells that make platelets (which form blood clots to help slow or stop bleeding). CML is also called chronic myelogenous leukemia, chronic myelocytic leukemia, and chronic granulocytic leukemia.

Who Gets Chronic Myeloid Leukemia?

Just over 9,000 people are expected to be diagnosed with CML in the United States in 2021. Around 15 percent of people who have leukemia have CML. Most people with CML are older adults — nearly half of people diagnosed with CML are at least 65 years old. Additionally, men are slightly more likely to get CML than women.

Causes of CML

Like other types of leukemia, CML develops when a blood cell’s genes become damaged. The damage leads to abnormalities that make the cell grow out of control. More than 19 out of 20 people with CML have a changed gene called the Philadelphia chromosome.

Chromosomes are long pieces of DNA that contain all of a cell’s genes. The Philadelphia chromosome is the result of a change called a translocation, in which pieces from two different chromosomes change places. In CML cells, chromosomes 9 and 22 are abnormally joined together, which forms a “fusion gene” called BCR-ABL. The BCR-ABL gene tells the cell to start making an abnormal protein, also called BCR-ABL, which causes the cell to grow out of control.

Risk Factors

Researchers have not found many major risk factors that lead to CML. Other than being older and male, the only additional CML risk factor that researchers have found is exposure to very high levels of radiation, such as surviving a nuclear reactor accident or an atomic bomb blast. In most cases, it’s not clear why a person is diagnosed with CML.

Chronic Myeloid Leukemia Symptoms

CML can cause some general symptoms such as fever, night sweats, weight loss, and bone pain. It may also lead to splenomegaly (an enlarged spleen), which can result in pain or fullness underneath the ribs on the left side of the body. Many people with CML also have symptoms related to abnormally low levels of blood cells, as follows:

  • Anemia (low red blood cell levels), which leads to tiredness, dizziness, pale skin, and shortness of breath
  • Neutropenia (low levels of neutrophils, a type of white blood cell), which can cause infections
  • Thrombocytopenia (low platelet counts) or thrombocytosis (high platelet counts), which can both lead to bruising or bleeding

These symptoms are also frequently caused by other conditions. Having any of these symptoms does not mean that you have CML. However, if you are experiencing any of them, you should talk to your doctor.

Read more about symptoms of CML.

Diagnosis of CML

Diagnostic tests can help a doctor check whether blood or bone marrow cells are cancerous. Once signs of cancerous bone marrow or blood cells have been found, doctors can use that data to determine what type of leukemia a person has. Doctors use different tools to diagnose CML:

  • A physical exam, which allows the doctor to look more closely at CML signs and symptoms
  • A complete blood count (CBC), which measures the numbers of each type of blood cell.
  • Blood chemistry tests, which are used to check for molecules in the blood that may also be signs of cancer
  • A bone marrow biopsy (removal of a small sample of cells) and bone marrow aspiration (removal of fluid), which allow the doctor to look for leukemia cells in the bone marrow
  • Laboratory tests, which doctors use to look for gene or chromosome changes, such as karyotyping, fluorescence in situ hybridization (FISH), or polymerase chain reaction (PCR)

These tests are used to diagnose the type of leukemia a person has, estimate their prognosis, and devise a treatment plan.

Chronic Myeloid Leukemia Phases

Diagnostic tests for CML can also help doctors determine the phase of a person’s CML diagnosis. Different phases may be treated with different therapies and lead to different outlooks. A person’s phase is determined based on their levels of blasts (immature cells), blood cell counts, and chromosome changes. There are three CML phases:

  • Chronic phase — In this phase, the CML may not cause any symptoms and often responds well to treatments.
  • Accelerated phase — In this phase, the CML is more likely to cause symptoms and may not be controlled as well by treatments.
  • Blast phase (or blast crisis) — This phase often leads to more severe symptoms and is harder to treat.

Most people are diagnosed while their CML is in the chronic phase. Over time, chronic phase CML can turn into accelerated or blast phase CML, but treatments can often prevent this.

CML Treatments

A person’s treatment plan is often based on several factors, including age, overall health, levels of blast cells, and CML phase. People with Philadelphia chromosome-positive CML take medications called tyrosine kinase inhibitors (TKIs). TKIs are a type of targeted therapy that block the BCR-ABL protein. Without BCR-ABL, leukemia cells die. These drugs are very effective at treating CML and preventing it from coming back.

Most people take TKIs for the rest of their lives to keep their leukemia from returning. TKIs come in the form of a tablet or capsule that is taken by mouth, at home, each day. There are five TKIs approved by the U.S. Food and Drug Administration to treat CML:

Because TKIs usually work so well, doctors don’t use other drugs as often. However, in some cases, another treatment option is needed. If someone has CML that is refractory (resistant) to TKIs, a chemotherapy drug called Synribo (omacetaxine mepesuccinate) may help. Additionally, drugs such as Intron A (interferon alfa-2b) can be used by people who can’t take TKIs, including people who are pregnant.

In very rare instances, a person with CML will need an allogeneic stem cell transplant. During this procedure, a person with CML undergoes high doses of chemotherapy or radiation therapy to kill their bone marrow cells. They then receive new bone marrow cells from a donor. These new cells can make healthy blood cells that can replace the ones lost during high-dose treatment.

Read more about treatment options for CML.

What Is the Outlook for Chronic Myeloid Leukemia?

CML used to be a very serious disease. Now, effective TKI drugs can keep this leukemia under control for many years, leading to a better outlook. About 7 out of 10 people with CML will live for five years or more after being diagnosed.

A person’s prognosis (outlook) with CML depends on many factors. Factors that make a person more likely to have a poor outcome include:

  • Older age
  • Accelerated or blast phase CML
  • High levels of blasts in the blood or bone marrow
  • High white blood cell counts
  • Low red blood cell count
  • Very low or very high platelet counts
  • Splenomegaly
  • Certain gene or chromosome changes
  • High levels of lactate dehydrogenase (LDH) in the blood
  • Other health conditions

Estimating a person’s outlook can be complicated. If you are interested in learning more about your own prognosis, talk to your doctors. Your health care team can help you understand how your individual characteristics can affect your CML.

Read more about survival rate and outlook for CML.

Talk With Others Who Understand

MyLeukemiaTeam is the social network for people with leukemia and their loved ones. On MyLeukemiaTeam, members come together to ask questions, give advice, and share their stories with others who understand life with leukemia.

Are you living with chronic myeloid leukemia? Share your experiences in the comments below, or start a conversation by posting on your Activities page.

Todd Gersten, M.D. is a hematologist-oncologist at the Florida Cancer Specialists & Research Institute in Wellington, Florida. Review provided by VeriMed Healthcare Network. Learn more about him here.
Maureen McNulty studied molecular genetics and English at Ohio State University. Learn more about her here.

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