• Chronic Myeloid Leukemia (CML)

    Chronic myelogenous leukemia, also called chronic myeloid leukemia or CML, is a form of leukemia (blood cancer) that develops in the bone marrow, the soft, spongy center of long bones. CML is a cancer of a subtype of white blood cell called a “myeloblast”. Normal myoblasts grow, divide and mature into white blood cells capable of fighting infections. This process is controlled by the body through complex signaling networks. In a patient with CML, the bone marrow makes abnormal myeloblasts that don’t respond to these normal signals and as a result produce large amounts of abnormal white blood cells in an uncontrolled manner. These abnormal cells do not fight infections, but spill into the blood in large numbers, causing a variety of serious problems.

    CML is very rare in children. Approximately 150 children in the U.S. are diagnosed with CML each year.

    Chronic Myelogenous Leukemia (CML) Treatment at Dana-Farber/Boston Children's

    Children and adolescents with CML are treated at Dana-Farber/Boston Children's through our Hematologic Malignancy Center's Leukemia Program. Dana-Farber/Boston Children’s has played a key role in refining treatment for childhood leukemia, and we continue to be a world leader in leukemia clinical trials designed to increase cure rates, decrease treatment-related side effects and improve care for long-term survivors. The Leukemia Program also offers families the chance to have their child's leukemia cells molecularly profiled, which may help identify opportunities for targeted treatment.

    What are the phases of CML?

    Chronic myelogenous leukemia (CML) can be diagnosed in three distinct phases, or stages of development:

    • Chronic phase – During this period, there may be no, or few, symptoms of leukemia. However, abnormal types and numbers of cells are discovered in the blood and bone marrow. This phase can last several months to several years.
    • Accelerated phase – In this period, an increased number of “blast cells” are found in the blood and bone marrow. The presence of blasts cells indicates the disease is becoming more aggressive or advanced.
    • Blastic phase (also known as a "blast crisis") – During this phase more than 30 percent of bone marrow cells are blast cells. This phase of CML can be very difficult to differentiate from acute lymphoblastic leukemia.

    What causes chronic myelogenous leukemia (CML)?

    It is not known what causes leukemia, including CML. In the majority of childhood leukemias, gene mutations and chromosome abnormalities in the leukemia cells occur by chance. The abnormalities found in leukemia cells are not found in the other cells of the body.

    Nearly all cases of CML are associated with a specific type of genetic abnormality called a chromosomal translocation. In this translocation, part of chromosome #9 breaks off and attaches itself to part of chromosome #22. The resulting abnormal chromosome, often called the “Philadelphia chromosome”, forms an abnormal gene called BCR-ABL. This gene makes an abnormal protein which drives the development of the abnormal myeloblasts.

    What are chronic myelogenous leukemia (CML) symptoms?

    The symptoms of CML are related to the phase of the disease and often vary from child to child. Patients with chronic phase CML sometimes have no symptoms of the disease, and can be discovered when your child is having a routine blood test for other reasons. Patients in the accelerated phase or blast crisis often have symptoms related to abnormal bone marrow function:

    While CML symptoms may vary child-to-child, the most common include:

    Chronic phase CML symptoms

    • General fatigue and weakness
    • Abdominal pain may be a symptom of leukemia, since leukemia cells can infiltrate into your liver and spleen, causing enlargement of these organs. Pain in the abdomen may cause your child to lose his appetite, and lose weight.
    • Recurrent infections. Although your child may have an unusually high number of white blood cells, these cells are immature and do not fight infection. Your child may have had several viral or bacterial infections over the past few weeks, and may show symptoms of an infection such as fever, runny nose and cough.

    Accelerated or blast phase CML symptoms

    • Abnormal bleeding or easy bruising as a result of decreased production of platelets in the bone marrow.
    • Anemia as a result of decreased production of platelets in the bone marrow.
    • Serious infections as a result of decreased production of normal white blood cells in the bone marrow.
    • Bone and joint pain. Your child may experience pain in his bones and joints that results from the bone marrow being overcrowded and "full."
    • Swollen lymph nodes. Your child may have swelling in the lymph nodes under the arms, in the groin, chest and in the neck. Leukemia cells may collect in the nodes, causing swelling.

    It is important to understand that these are general symptoms of the disease, but do not include all possible symptoms. It’s important to have your child evaluated by a qualified medical professional right away for an accurate diagnosis and prompt treatment.

    How is chronic myelogenous leukemia (CML) diagnosed?

    Tests to make a CML diagnosis may include:

    • Complete medical history and physical exam.
    • Bone marrow aspiration and biopsy to remove and test bone marrow. In an aspiration biopsy, a fluid specimen is removed from the bone marrow. In a needle biopsy, a small piece of the bone marrow is removed.
    • Complete blood count. A measurement of the size, number, and maturity of different blood cells in a specific volume of your child’s blood.
    • Additional blood tests, which may include blood chemistries, evaluation of liver and kidney functions and genetic studies.
    • Spinal tap/lumbar puncture. A special needle is placed into the spinal canal in your child's lower back to measure the pressure in your child’s spinal canal and brain. A small amount of cerebral spinal fluid (called CSF – the fluid that bathes your child’s brain and spinal cord) can be removed and tested for infection or other problems.

    There may be other diagnostic tests that your doctor will discuss with you depending on your child's individual situation. After we complete all necessary tests, our experts meet to review and discuss what they have learned about your child's condition. Then we will meet with you and your family to discuss the results and outline the best possible treatment options, including clinical trials if applicable.

    What are chronic myelogenous leukemia (CML) treatments?

    CML treatment depends on your child’s individual situation, including the specific phase of the disease.

    Chronic Phase CML

    Children diagnosed with chronic phase CML are most often treated with tyrosine kinase inhibitors (TKIs). Children with chronic phase CML do not receive chemotherapy and only rarely undergo a stem cell transplant.

    • Tyrosine-Kinase Inhibitors (TKI) are drugs that target a particular gene alteration that is known to cause CML. These drug types include Imatinib (Gleevec), Dasatinib, Nilotinib, Bosutinib and Ponatinib. (Most children with CML will take Imatinib. However, if your child has specific genetic alterations that don’t respond to Imatinib, they may try Dasatinib or Nilotinib. Bosutinib and Ponatinib are very rarely used for children.)
    • Stem cell transplant was once the only treatment option for patients in chronic phase CML, but today stem cell transplant at this phase has become rare and is largely reserved for patient who are resistant or intolerant of TKI treatment. Stem cell transplant involves replacing your child's stem cells – a specific type of cells from which blood cells develop – with healthy stem cells from another person. When your child's stem cells are replaced with those of a healthy and compatible donor, it is called allogeneic transplantation. Treatment may begin with high-dose chemotherapy (perhaps combined with radiation therapy) to destroy all of the bone marrow, stem cells and cancerous cells, in your child's body. Then, healthy stem cells from another person (whose tissue must be the same, or almost the same as your child's) are used to help restore your child's normal blood production.

    Accelerated Phase and Blast Crisis CML

    Patients diagnosed with accelerated phase CML or blast crisis will need initial treatment with TKIs and chemotherapy. If your child’s disease continues to progress, however, the next stage of treatment will be stem cell transplant.

    • Tyrosine-Kinase Inhibitors (TKI) (see description above)
    • Chemotherapy is a drug treatment that works by interfering with the cancer cell's ability to grow or reproduce. Different groups of chemotherapy drugs work in different ways. Your child may receive chemotherapy orally, as a pill to swallow; subcutaneously, as an injection below the skin; intravenously, as a direct injection into the bloodstream, or IV; or intrathecally, as a direct injection into the spinal column through a needle.
    • Stem cell transplant(see description above)

    Supportive Care

    Treatment for CML can cause various side effects. Supportive care will be provided to keep your child as healthy and strong as possible throughout treatment.

    • Blood transfusions are often given to replace or supplement your child's red blood cells and platelets.
    • Antibiotics may be given to your child to prevent or treat infections.
    • Other medications may be given to prevent or treat damage to other systems of your child's body caused by leukemia treatment, or for nausea and side effects of treatment.

    Of course, your child's team of doctors will help determine the best approach for your child's unique situation, based on a number of factors including:

    • Your child's age, overall health and medical history
    • The extent of the disease
    • Your child's tolerance for certain medications, procedures or therapies
    • How your child's doctors expect the disease to progress
    • Your opinion and preferences

    What is the latest chronic myelogenous leukemia (CML) research?

    Both Dana-Farber Cancer Institute and Boston Children's Hospital are among the top pediatric research centers in the world for pediatric leukemia, including CML. Our research programs include laboratory scientists and clinical researchers.

    Much of our current leukemia research is focused on trying to better understand the genetic underpinnings of leukemias, including CML. The physician scientists in our programs provide free on-site genomic sequencing of all leukemias (using blood samples obtained during diagnostic testing).

    Genomic sequencing can help provide insights into complex diseases by finding common genetic variants (mutations) shared between the individuals with the disease. Once the specific mutations are discovered, it may then be possible to develop drugs that can counteract those mutations.

    Tyrosine-Kinase Inhibitors (TKIs), which are used to treat CML, are one type of targeted therapy designed to counteract specific genetic mutations that cause CML. However, some children may have additional genetic mutations for which there are not yet targeted therapies available, and not all children respond to TKIs. Ongoing research is needed to build greater understanding of the various genetic alterations involved in CML (and other leukemias) and to develop drugs to target those genetic variants. Ultimately, someday we may be able to treat CML without ever needing stem cell transplant.

    Clinical Trials

    For many children with rare or hard-to-treat conditions, clinical trials provide new options. Participation in any clinical trial is completely voluntary. We will take care to fully explain all elements of the treatment plan prior to the start of the trial, and you may remove your child from the medical study at any time.

    What is the long-term outlook for children with CML?

    Your child's prognosis greatly depends on the extent of the disease, the cancer's response to treatment and the leukemia's particular genetic abnormalities. Also important is your child's age and overall health and tolerance for specific medications, procedures or therapies.

    As with any cancer, prognosis and long-term survival can vary greatly. Prompt medical attention and aggressive therapy are important for the best prognosis, and continuous follow-up care is essential. New methods are continually being discovered to improve treatment and decrease side effects of CML treatment.

    Relapse can occur during any stage of treatment, even with aggressive therapy, or may occur months or years after treatment has ended. If CML recurs, the treatment plan often includes targeted therapy (drugs, such as TKIs, that specifically attack a molecular pathway required to keep a tumor growing), chemotherapy and immunotherapy (treatment that stimulates the immune system to reject and destroy a tumor).

    Follow-up Care

    Continuous follow-up care is essential for any child diagnosed with leukemia, including CML. However, the specific type of care needed will depend on the type of treatment your child received or is receiving.

    Children who are able to manage their disease through TKIs will need to follow up regularly with their clinical care team to monitor their disease and to assess potential side effects.

    Children who are cured of CML through stem cell transplant or other therapies will need ongoing cancer survivorship care. Side effects of chemotherapy, as well as second malignancies, can occur in survivors of CML. Our cancer survivorship clinic, which set the national standard for childhood cancer survivorship care, offers ongoing care to manage late effects caused by your child’s cancer or the treatment they received.

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