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.
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
Chronic myelogenous leukemia (CML) can be diagnosed in three
distinct phases, or stages of development:
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
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
Accelerated or blast phase CML symptoms
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.
Tests to make a CML diagnosis may include:
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
depends on your child’s individual situation, including the specific phase of
Chronic Phase CML
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.
Accelerated Phase and Blast Crisis CML
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.
Treatment for CML can cause various side effects. Supportive
care will be provided to keep your child as healthy and strong as possible
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
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
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.
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.
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
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
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.
Leslie Lehmann, MD, explains stem cell transplants. Dana-Farber/Boston Children's has one of the most experienced pediatric stem cell transplant programs in the United States.