Chronic myelogenous leukemia (CML)

CML is rare in children, accounting for less than 5 percent of all childhood leukemias.
It is characterized by a very large spleen, high white count of mostly neutrophils and
other types of granulocytes, and a high platelet count. Other symptoms of CML are
fatigue, weakness, headaches, irritability, fevers, night sweats, and bone pain. Some
children have no symptoms and the cancer is diagnosed after a routine blood test
done for other reasons.
In over 90 percent of children with CML, analysis of the cells of the bone marrow
shows a genetic abnormality called the Philadelphia chromosome. This chromosome
contains a “translocation” or swap of genetic material involving chromosomes 9 and
22, abbreviated as t(9;22).
Phases of CML
Despite its name, CML can progress rapidly, but it generally has three phases:
• A chronic phase (less than 5 percent blasts in the peripheral blood or bone
marrow), which generally lasts 3 to 5 years.
• An accelerated phase (greater than 5 percent but less than 30 percent blasts in the
peripheral blood or bone marrow). This phase can begin gradually or abruptly.
Symptoms include fever, night sweats, weight loss, and increase in white blood
cell counts.
• A blastic phase (greater than 30 percent blasts in the peripheral blood or bone
marrow). Symptoms of blastic phase (also called blast crisis) include fever,
fatigue, and enlarged spleen.
Leah, 11 years old, enjoyed participating in basketball, soccer, and
gymnastics. She developed severe hip joint pain, and we brought her back
to the doctor three times in an unsuccessful attempt to find out what was
wrong. The last time, my husband had to carry her in because she
couldn’t walk. They did blood work, and her white count was 176,000
and her platelets were one million. A bone marrow test confirmed that
she had CML.
Treatment for children with CML
The goal of initial treatment is to lower the white count and reduce the size of the
spleen and liver. This is accomplished by taking oral medications, historically either
hydroxyurea or busulfan (also called Myleran). More recently, STI-571 (Gleevec) or
the biologic agent interferon alfa are being used. Patients with a complete response
(normal physical examination, normal blood counts and bone marrow, disappear-
ance of the Philadelphia chromosome) will have a prolongation of the chronic phase of
their disease. Some may even be cured. However, most children do not achieve a com-
plete remission. The early experience with Gleevec suggests that a higher percentage of
children may achieve complete remissions. However, follow-up of these children is
very short, so it is not certain how long these remissions will last.
If the spleen does not shrink after treatment with drugs or radiation, surgical removal
may be required.
Although medications may slow the progress of CML, the best hope for cure is bone
marrow transplantation. The highest cure rates (60 to 80 percent) occur when the
child is transplanted with marrow or blood stem cells from an HLA-identical (or
closely matched) family member less than one year from initial diagnosis during the
chronic phase. Use of a well-matched unrelated donor gives similar results. Refer to
Chapter 20 for detailed information.
The second stage or “accelerated phase” of CML is usually brief. The number of both
immature white blood cells and blast cells in the bloodstream increases. The number
of red blood cells drops and platelets may increase or decrease. In 2002, treatment for
this phase includes high-dose cytarabine, hydroxyurea, busulfan, and/or supportive
transfusion therapy (see Chapter 10). Stem cell transplants may be utilized, but the