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Chronic Myeloid Leukemia (CML)

What is Chronic Myeloid Leukemia?

Chronic myeloid leukemia is a cancer of the blood and bone marrow.

Leukemia occurs when the bone marrow makes too many cancer cells. These cells are called blasts. As blasts grow and divide rapidly, healthy blood cells cannot not do their jobs. The blood doesn’t function correctly. The patient cannot fight infection well.

CML is a chronic leukemia. It develops slowly over time. It may be weeks or months before children develop symptoms. In contrast, acute leukemias make children ill very quickly. Chronic also means that the leukemia may last over a long period of time.

CML is rare in children. Only 110-120 cases are seen each year in the United States and Canada. It makes up 2-3% of leukemia in children and teenagers.

About 90-95 percent of children with CML have a genetic alteration called the Philadelphia chromosome. Drugs called tyrosine kinase inhibitors (TKIs) are the first line of treatment.

Every human being normally has 23 pairs of chromosomes. They carry all the genetic information (genes) that make up a person. A mutation in genes or chromosomal changes may cause a disease such as cancer to occur.

The Philadelphia chromosome forms when a piece of chromosome 9 and a piece of chromosome 22 break off and trade places. A fusion of two genes bcr and abl (bcr-abl) is formed on chromosome 22 where the piece of chromosome 9 attaches. This fusion gene makes an enzyme called tyrosine kinase. It causes leukemia cells to grow and divide very quickly. Drugs called tyrosine kinase inhibitors (TKIs), which are designed to stop the enzyme, are the front line of therapy for CML.

The Philadelphia chromosome is not passed from parent to child. It occurs randomly and sporadically.

Signs and Symptoms of Chronic Myeloid Leukemia

CML develops slowly. Children with CML may not have symptoms at first.

Common symptoms include:

  • Fatigue
  • Weight loss
  • Fever
  • Night sweats
  • Pain or feeling of fullness under the rib cage
  • Bone and joint pain

Diagnosis of Chronic Myeloid Leukemia

Tests to diagnose CML may include:

  1. During the physical exam, the doctor will check general signs of health. The doctor will look for signs of disease, such as lumps or anything else that seems unusual. He or she will feel the patient’s abdomen for signs of an enlarged spleen or liver.

    The doctor will examine the eyes, mouth, skin, and ears. He or she may conduct a nervous system exam.

    Sometimes doctors will order diagnostic imaging tests.

  2. Results of blood and bone marrow tests suggest the diagnosis of CML.

    A young patient sits on an exam table with her parents nearby while a nurse draws a blood sample.

    Doctors may begin to suspect leukemia after conducting a physical exam, taking a medical history, and looking at the results of blood tests.

If tests indicate cancer, doctors will order more tests to pinpoint the type. These tests may include:

  • Immunophenotyping
  • Cytogenetic analysis
  • Molecular and genetic testing
  1. Immunohistochemistry and flow cytometry are the laboratory tests. These tests diagnosis specific types of leukemia by comparing the cancer cells to normal cells.

    • Immunohistochemistry is a test that uses antibodies to show specific proteins in a tissue sample. The complexes of proteins and antibodies are stained brown or red and can be seen under a microscope.
    • In flow cytometry, cells are stained with a light-sensitive dye, placed in a fluid, and passed in a stream before a laser or other type of light. The test measures the:
      • Number of cells
      • Percentage of live cells
      • Certain characteristics of cells, such as size, shape, and the presence of tumor markers on the cell surface
  2. Cytogenetic analysis involves laboratory tests in which pathologists look for certain changes in the chromosomes.

    One such test is FISH (fluorescence in situ hybridization). This test looks at genes or chromosomes in cells and tissues. Pieces of DNA that contain a fluorescent dye are made in the laboratory. They are added to cells or tissues on a glass slide. These pieces of DNA light up when attached to certain genes or areas of chromosomes on the slide.

  3. The doctor may recommend laboratory tests to identify specific genes, proteins, and other factors involved in the leukemia. This examination is important because cancer is caused by mistakes (mutations) in the cell’s genes.

    In CML, a test called PCR is used. PCR stands for polymerase chain reaction. PCR can detect presence of BCR-ABL1, the fusion gene that is the hallmark of CML. Molecular testing is critical to confirm the diagnosis and to see the response (or lack of response) to therapy.

    Doctors can use the test results to identify:

    • Cases at high-risk of progression
    • Cases unlikely to respond to TKI drugs
    • Patients who could be eligible to stop therapy

    This information helps doctors guide treatment.

Phases of Chronic Myeloid Leukemia

CML has 3 phases. The phase depends on the number of leukemia (blast) cells in the blood and bone marrow.

  • Chronic: Fewer than 10% blasts
  • Accelerated: 10-19% blasts
  • Blastic: 20% or more blasts. During the blast crisis patients have tiredness, fever, and an enlarged liver and spleen.

Treatment for Chronic Myeloid Leukemia

Treatment depends on the phase of the cancer.

First-line treatment for CML is usually the drug imatinib (Gleevec®). It is a tyrosine kinase inhibitor (TKI). It can stop the enzyme, tyrosine kinase. This enzyme causes cancer cells to grow out of control.

Other TKI drugs called dasatinib and nilotinib are sometimes used if patients can’t tolerate imatinib. These drugs are sometimes referred to as 2nd generation TKIs.

During treatment, doctors closely watch how patients respond to therapy. This is called monitoring.

Monitoring may include a medical history, physical exam, complete blood count, cytogenetic analysis and molecular testing.

Molecular tests are performed every 3 to 6 months after the start of therapy.

Molecular testing can measure the number of leukemia cells in blood. It can detect one leukemia cell among 10,000 normal cells.

Testing can also detect changes in CML cells. After taking a TKI drug, CML cells may change. The change may mean the medicine won’t work as well. Doctors can use the information to guide treatment.

Patients may need to take TKIs for the rest of their lives to treat their CML. It is not yet known what long-term side effects the drugs may have.

Children may face unique side effects not seen in adults, such as growth problems, because they are actively growing during treatment with TKI drugs. Long-term effects on puberty and fertility are not known. Patients and families are encouraged to talk to their care team about possible side effects.

Hematopoietic cell transplant

A hematopoietic cell transplant (also known as bone marrow transplant or stem cell transplant) is another treatment option for CML.

A transplant can cure CML. However, the patient must have a suitable cell donor.

Transplant can have serious side effects.

Prognosis of Chronic Myeloid Leukemia

When discussing prognosis, doctors often use a number called the 5-year survival rate. This rate is the percentage of patients who live at least 5 years after diagnosis.

For chronic leukemias, 5-year survival rates are less helpful because children may live for a long time with leukemia without actually being cured. Five-year survival rates for pediatric chronic myeloid leukemia (CML) are 90%.

Focus of Current Chronic Myeloid Leukemia Research

  • New treatment approaches to cure CML. Research question: Is it possible to eliminate CML cells with other treatments?
  • Reducing side effects of TKI medicines — There are several side effects associated with the prolonged use of TKIs in children. These include problems with growth, development, and fertility. Research question: Is it possible to intervene early in the treatment course to reduce these complications?
  • Score system for prognosis in children — Prognosis is based on the adult experience. Researchers seek to develop and implement a score system for prognosis in children.
  • TKI medicine dosage — There is a subset of children who have been in remission for a prolonged time. Research questions: Is it possible to stop or modify the dosage of TKI drugs? Which patients are the best candidates to stop the medication? Is there a possibility of reducing the dose of the medication?
  • Pediatric CML registry — The history has not been established for treating CML in children with TKI for a long time. Research question: Is it possible to create a pediatric CML registry to follow these patients for life?


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Reviewed: September 2019