Acute lymphoblastic leukemia (ALL) 2

Approximately 15 percent of children with ALL have T-cell ALL. T-cell ALL has one
or more of the following antigens on the surface of the cancer cells: CD2, CD7, CD5,
CD8, or CD3. Often, children with T-cell ALL are male, have high WBC counts, have
masses in their chests at diagnosis, and are over 10 years old. T-cell ALL requires
more intensive therapy, but outcomes after intensive therapy are similar to those for
B-lineage ALL.
Chromosome number
Normal cells have 46 chromosomes (22 pairs and the sex chromosomes—XX female
and XY male). Some leukemia cells contain extra copies of entire chromosomes and
thus can contain more than 46 chromosomes. This is called hyperdiploidy, and it is
found in approximately 27 percent of children with ALL. There are two ways to eval-
uate the number of chromosomes: counting them (karyotyping) or measuring the
DNA content of cells (DNA index). Children with 53 or more chromosomes per cell
or a DNA index greater than 1.16. have a very good prognosis. Hyperdiploidy occurs
most often with B-lineage ALL.
Extra copies of particular chromosomes also seem to indicate a very favorable prog-
nosis. Children with extra copies of chromosome 4, 10, and 17 have an especially
favorable prognosis.
Approximately 6 percent of children with ALL have fewer than 45 chromosomes in
the leukemia cells. This is called hypodiploidy and carries a poor prognosis.
Chromosome translocations
Sometimes genetic material is exchanged between chromosomes in leukemia cells.
This is called a translocation. Translocations are very common in childhood ALL, and
some of these are known to affect prognosis. Examples are:
• Movement of the TEL (ETV6) gene on chromosome 12 to the AML1 (CBFA2)
gene on chromosome 21. This is called the TEL-AML1 fusion and is found most
often in children between the ages of 2 and 9. Children with this translocation
usually have very good outcomes.
• The Philadelphia chromosome, called t(9;22), is found in approximately 3 to 4
percent of children with ALL. It is associated with a poor prognosis, especially in
older children with high white blood counts and a slow response to treatment.
• Translocations involving the MLL gene are found in 6 percent of children with
ALL. The most common MLL translocation is t(4;11). This occurs most often in
infants with CNS disease and high white blood counts at diagnosis. The t(11;19)
translocation is associated with a poor outcome in infants but a favorable out-
come in older children with T-cell leukemia and this translocation.
Response to treatment
How quickly the leukemia cells disappear after treatment starts is also a factor in the
child’s prognosis. Some institutions test the bone marrow on the seventh and the four-
teenth days of treatment. If a rapid reduction of blasts in the marrow has occurred
within the first two weeks of treatment, then the child is considered an “early rapid
responder” and may be placed onto a less intensive protocol (treatment plan). Other
centers use response to a one-week trial of prednisone to separate children into risk
categories. Scientists are now using special biochemical techniques to measure the
amount of leukemia remaining in the bone marrow after four weeks of chemotherapy.
This measure of residual leukemia (minimal residual disease—MRD) is 1,000 times
more sensitive than looking at the bone marrow with a microscope. Some institutions
now use MRD to help choose the most appropriate treatment.
All of the information above is used to determine what treatment is most appropriate
for your child. Children at low or average risk of relapse need fewer and less toxic
drugs than do those at high risk of relapse. However, most children with high-risk
disease do very well when given more intensive treatment.
Treatment for ALL
ALL is one of the most curable forms of childhood cancer. To receive the best avail-
able treatment, it is essential that the child with ALL be treated at a pediatric medical
center by board-certified pediatric oncologists with extensive experience treating acute
leukemia. The intense treatment for ALL begins within days of diagnosis and requires
aggressive supportive care. The goal of treatment is to achieve a complete remission by
obliterating all leukemia cells as quickly as possible. Complete remission occurs when
all signs and symptoms of leukemia disappear and abnormal cells are no longer found
in the blood, bone marrow, or cerebrospinal fluid.
The primary treatment for ALL is chemotherapy—the use of drugs especially
designed to kill cancerous cells. Radiation of the brain and sometimes of the spinal
cord is administered to some very high-risk patients. Bone marrow transplantation
from an HLA-matched sibling is sometimes used to treat children with very high-risk
disease (children with the Philadelphia chromosome or hypodiploid cancer cells) or
children who have had a relapse (recurrence) of their leukemia. Infants with ALL
require special treatment plans.
Treatment is usually divided into phases: induction, central nervous system prophy-
laxis, consolidation, reinduction, reconsolidation, and maintenance (also called contin-
uation). Children with extremely high white blood cell counts at diagnosis may
require leukapheresis (removal of the white blood cells) before treatment with chemo-
therapy begins.
Induction
Induction is the initial phase of treatment. Its purpose is to kill as many abnormal
white cells in the shortest amount of time possible. It usually lasts four weeks, and for
a portion of that time, children may need to remain hospitalized for monitoring and
transfusions. For the remainder of the time, children are treated on an outpatient
basis unless a complication arises. Children may need to be readmitted on more than
one occasion during induction due to fever, infection, or other complications.
Chemotherapy is most effective if three or four drugs are used simultaneously. In
2002, the majority of standard-risk ALL induction programs include vincristine,
prednisone or dexamethasone, and asparaginase. An anthracycline (daunorubicin,
idarubicin, or epirubicin) is often added to high-risk protocols. Drugs are given intra-
venously (through a needle or tube in the vein), intramuscularly (injection in muscle),
orally (by mouth), or intrathecally (injected into the cerebrospinal fluid). These drugs
can cause numerous side effects. See Chapter 10, Chemotherapy , for an in-depth dis-
cussion of each drug and its side effects.
Ninety-eight percent of children with ALL who receive three or more drugs during
induction achieve a complete remission.
CNS prophylaxis
The central nervous system (CNS) is composed of the brain and spinal cord, which
are bathed in a fluid called cerebrospinal fluid (CSF). When cancer invades the brain,
cancer cells are found in the CSF. In most cases of childhood ALL (96 percent),
leukemia cells are not found in the CSF at the time of initial diagnosis of ALL. How-
ever, before it became standard practice to use CNS prophylaxis (prevention), 60 to
70 percent of children with ALL eventually developed leukemia in the central nervous
system. This suggests that at the time of diagnosis, microscopic amounts of leukemia
are already present in the CNS. Therefore, CNS prophylaxis is now an essential part
of treatment for ALL.