Introduction
Causes
of Acute Lymphoblastic Leukemia
Symptoms
Treatment
Prognostic Features
Disease Recurrence
Long-term Complications of Leukemia
Treatment
Future Directives
Introduction
Acute lymphoblastic leukemia (ALL) is the most common
cancer in children. It is a blood cancer that affects the infection fighting
cells of the body known as white blood cells. Approximately 1,600 new cases
are diagnosed annually in the United States. Through the tireless endeavors
of cooperative study groups, the current cure rate of Acute Lymphoblastic
Leukemia (ALL) is 80%. In this article, I will discuss the causes, symptoms,
treatment, disease recurrence, long-term complications, and future directives
of childhood ALL.
Causes
of Acute Lymphoblastic Leukemia
In most children the cause of ALL has remained elusive
despite intense research efforts. Current clinical wisdom points towards
a viral cause. In fact, some oncologists (cancer specialists) believe that
viral exposure while the child is still in the mother's uterus sets the
stage for leukemia formation. This philosophy is reinforced by the finding
of identical leukemia markers at diagnosis and from newborn screening blood
samples. Further work is needed in this important area of investigation.
Children with certain genetic (or chromosome) disorders
(Down Syndrome, ataxia-telangiectasia, etc.) and/or immune system problems
(x-linked severe combined immune deficiency, Wiskott-Aldrich syndrome,
etc.) are at an increased risk of developing ALL. In some of these rare
disorders the underlying mechanisms resulting in cancer are being unraveled.
Symptoms
Children with ALL usually get bone marrow failure. The
bone marrow produces the various cells in the blood. The symptoms that
a child with ALL experiences are primarily due to the dramatic decrease
in the numbers of these blood cells. Anemia (decreased activity and appetite,
pale appearance), easy bruising, bleeding from the nose and gums, infections
and mouth ulcers may all occur. Other signs and symptoms include fever,
back pain, bone pain, the inability to walk, enlarged neck glands, enlarged
testicles, headaches and rarely, metabolic (sodium and potassium) imbalances.
Diagnosis
These clinical findings prompt the pediatrician to perform
a blood test called a complete blood count. If his or her suspicion is
confirmed (by low blood counts), the next step is to refer the child to
a pediatric cancer specialist.
As a pediatric oncologist, when I see such a child, I
prepare the child and family for the next step - a bone marrow aspirate.
This involves placing a special needle through the skin (after it is "numbed
up" with local anesthesia) and into a bone to draw out a sample of marrow.
The specimen is examined under a microscope and the results are ready within
an hour. If the diagnosis of leukemia is made, I meet with the family to
discuss the diagnosis and the therapeutic options available. Many parents
believe that if they had taken their child to the pediatrician sooner the
leukemia could have been stopped. This not true. It is important for parents
to know that the leukemia is not their fault (or their pediatrician's)
and there is nothing they could have done to prevent it from occurring.
Treatment
With contemporary chemotherapy, 80% of children with
ALL can be cured. Boys generally receive therapy for three years (because
of the tendency for cancer relapse in the testicles) and girls for two
years. The goal of therapy is to achieve remission (destroying the leukemia
and allowing normal blood cells to regain control of the bone marrow) and
maintain that remission. Almost all children achieve a remission -
however, for a significant minority of children the leukemia relapses (or
comes back) and becomes more difficult to treat.
Chemotherapy (or cancer medications) can be given by
mouth, into a vein, into the muscle, and into the fluid that covers the
brain and spinal cord. Chemotherapy medications have given us the best
treatment results. The side effects of chemotherapy include hair loss,
nausea, and bone marrow suppression. Although most children will experience
these side effects, the degree to which each individual child is affected
is different and unpredictable.
Radiation therapy is reserved for children with disease
in the brain and/or spinal cord (a.k.a. the central nervous system) and
for boys with testicular leukemia.
Prognostic
Features
A panel of pediatric oncologists convened to determine
clinical prognostic features that could guide therapy and predict the chance
of cure. It was determined that for a child between the ages of 1 and 9,
with a white blood cell count in a non-critical range, an excellent outcome
could be predicted. Moreover, specific genetic features (e.g. chromosomal
translocations and DNA content) of the cancer were also determined to be
of prognostic significance. Using these features we can provide risk-directed
therapy. Therefore, we can reduce or eliminate the exposure of potentially
dangerous drugs to children predicted to have an excellent outcome, and
reserve newer therapies for children with a poorer predicted outcome. Some
features of specific cancer cells can lend themselves to novel therapies
and can provide a way to monitor for early recurrence of the leukemia.
Active research is underway to explore these areas.
Disease
Recurrence
Leukemia recurrence usually occurs while the child is
receiving chemotherapy or within one year of stopping therapy. It is rare
for leukemia to come back after the child has been in remission for more
than four years. Clearly, a recurrence is devastating news to the child
and family. A leukemia relapse usually portends a poor prognosis. Bone
marrow transplantation may be the only curative therapy available. However,
relapses outside the bone marrow, namely those occurring in the central
nervous system and testes, may be cured with chemotherapy and radiation.
We need better mechanisms to detect minimal quantities of leukemia so that
a relapse can be detected earlier and appropriate treatment can be given.
Long-term
Complications of Leukemia Treatment
Not too long ago the philosophy of pediatric oncologists
was to cure at all costs. Today, with a cure rate of 80%, we now worry
about long-term complications of treatment and must attempt a cure with
minimal cost. In this section I will discuss some long-term complications
of leukemia treatment.
Heart Damage
Some effective chemotherapy drugs can cause heart damage,
especially in young girls who receive high doses. This may result in "heart
failure". If your child is to receive these medications, special heart
tests will be performed before, during and/or after treatment. These tests
enable us to detect any pre-existing heart conditions and to monitor for
early heart damage.
Infertility
The ovaries and testes of prepubescent girls and boys
are resistant to the sterilizing effects of chemotherapy. However, once
these organs become active during puberty, they are at risk for chemotherapy-induced
damage that may result in permanent infertility. In these cases, I recommend
that sperm banking and egg collection be performed before chemotherapy
begins, and I refer families to the appropriate programs. I also tell parents
that chemotherapy and the diagnosis of cancer will not lead to birth defects
in their grandchildren.
Intelligence
We all want our children to perform well scholastically.
For the few children with central nervous system leukemia, radiation remains
the mainstay of therapy. This therapy, though effective, may decrease the
IQ and cause learning difficulties. Interestingly, a study in infants with
leukemia showed that very high doses of systemic chemotherapy eliminates
the need for radiation. Hopefully, these findings can make radiation a
therapy of the past.
Second Cancers
The risk of developing a second cancer is increased by
many chemotherapy medications and usually implies a poor prognosis. The
second cancer may be a new leukemia or a totally different type of cancer.
Investigators at St. Jude Children's Research Hospital and I described
the outcomes of children with a unique type of secondary leukemia. Almost
all of these children died from the secondary leukemia. Currently, bone
marrow transplantation offers the best change of cure. Because of
examples like this, we constantly re-evaluate the therapy we give children
and try to limit the exposure of cancer-causing medications.
Future
Directives
Our research goals are to better understand the causes
and mechanisms of leukemia, to improve survival with minimal or no long-term
complications, and to better identify children at risk for relapse. Researchers
are now identifying and describing leukemia-specific markers (cell components
that can distinguish leukemia cells) in the hope that this will result
in better therapies and improved survival. Moreover, these unique leukemia-specific
markers can be used to assess response to anti-leukemia therapy, and possibly
predict an impending relapse. Researchers are currently working on how
we can improve our ability to predict a leukemia relapse, and hopefully
translate that into an improved cure rate.
RELATED PROGRAMS
