| ACUTE LYMPHOCYTIC LEUKEMIA
What Is Acute Lymphocytic
Leukemia?
Leukemia is a type of cancer that starts in the soft,
inner part of the bones (bone marrow) and often moves
quickly into the blood. It can then spread to other
parts of the body such as the lymph nodes, the spleen,
liver, central nervous system and other organs. In contrast,
other types of cancer can start in these organs and
then spread to the bone marrow (or elsewhere). Those
cancers are not leukemia. Both children and adults can
get leukemia.
"Acute" means that the cancer develops quickly,
and if not treated, could be fatal in a few months.
"Lymphocytic" (limf-o-sit-ik) means that the
cancer starts from cells called lymphocytes (limf-o-sites).
Acute lymphocytic leukemia (ALL) is a type of cancer
that starts from these white blood cells in the bone
marrow.
Leukemia is a complex disease with many different types
and sub-types. The kind of treatment given and the outlook
for the person with leukemia vary greatly according
to the exact type and other factors.
Normal Bone Marrow and Lymphoid
Tissue
In order to understand the different types of leukemia,
it helps to have some basic knowledge of the blood and
lymph (limf) systems.
Bone marrow is the soft, spongy, inner
part of bones. All of the different types of blood cells
are made in the bone marrow. Bone marrow is made up
of blood-forming cells, fat cells, and tissues that
aid the growth of blood cells. Early blood cells are
called blood-forming stem cells. These stem cells grow
in an orderly process to produce red blood cells, white
blood cells, and platelets. (They are different from
embryonic stem cells which are formed from a developing
fetus and can develop into other kinds of cells in the
body.)
Red blood cells carry oxygen from
the lungs to all other tissues of the body. They also
carry away carbon dioxide, a waste product of cell activity.
A shortage of red blood cells causes weakness, shortness
of breath, and tiredness.
Platelets are actually pieces that
break off from certain bone marrow cells. They are called
platelets because they look a little bit like plates
when seen under the microscope. Platelets help stop
bleeding by plugging up areas of blood vessels damaged
by cuts or bruises.
White blood cells help defend the
body against germs – viruses and bacteria.
There are quite a few types of white blood cells. Each
has a special role to play in protecting the body against
infection. The 3 main types of white blood cells are
granulocytes, monocytes, and lymphocytes. The suffix
-cyte means cell.
The immune system is made up mainly of lymphoid tissue
(also known as lymphatic tissue). Lymphoid tissue is found
in many places throughout the body, including the lymph
nodes, the thymus, the spleen, the tonsils and adenoids,
and the bone marrow.
The lymphatic system consists of lymph vessels, lymph
nodes, and lymph fluid. Lymph vessels are like veins except
that they carry a clear fluid (lymph) instead of blood.
Lymph fluid contains excess fluid from tissues, waste
products, and immune system cells.
The main cell type that forms lymphoid tissue is the lymphocyte.
The two main types of lymphocytes are called B-cells and
T-cells. Normal T-cells and B-cells do different jobs
within the immune system.
Any of the blood-forming or lymphoid cells can turn into
a leukemic cell. Once that happens, the cell can reproduce
to form many new cancer cells. Eventually, these cells
can overwhelm the bone marrow, spill out into the bloodstream,
and spread to other organs. Acute lymphocytic leukemia
starts from early forms of the lymphocytes.
The Different Types of Leukemia
There are 4 major types of leukemia:
• acute and chronic
• lymphocytic and myeloid
In acute leukemia, the bone marrow cells don’t mature
properly. These immature cells continue to reproduce and
crowd out normal cells. Some types of acute leukemia respond
well to treatment and many patients are cured. Other types
have a less favorable outlook.
In chronic leukemia the cells look mature, but they
are not really normal and they can’t fight infection
they way they should. Also, the cells live too long,
build up, and crowd out normal bone marrow cells.
Lymphocytic and myeloid (or myelogenous) refer to the
different cell types from which leukemias start. Lymphocytic
leukemias develop from lymphocytes in the bone marrow.
Myeloid leukemia mainly develops from other types of
white blood cells such as granulocytes or monocytes.
Most cases of leukemia can be sorted into 1 of the 4 main
types shown in the table below.
| Acute lymphocytic leukemia (ALL) |
Acute myeloid leukemia (AML) |
| Chronic lymphocytic leukemia (CLL) |
Chronic myeloid leukemia (CML) |
The purpose of this article is to provide an overview
of acute lymphocytic leukemia in adults only. More detailed
information about the other kinds of leukemia and leukemia
in children is also available from the American Cancer
Society.
How Many People Get Acute Lymphocytic
Leukemia?
In 2006 there will be about 35,070 new cases of all types
of leukemia in the United States. Of these, about 3,930
will be acute lymphocytic leukemia (ALL). Although this
is mainly a disease of children, about 1,300 cases will
be in adults. About 1,490 people will die of ALL in the
United States in 2006. Two-thirds of them will be adults.
The risk of ALL is lowest between the ages of 25 and 50
and then begins to pick up. African Americans are much
less likely to have ALL.
What Causes Acute Lymphocytic Leukemia
(ALL)? Can It Be Prevented?
The cause of most cases of ALL remains unknown at this
time. But some cases can be linked to certain risk factors.
A risk factor is something that increases a person's chance
of getting a disease. Some risk factors, like smoking,
can be controlled. Others, such as a person's age, can't
be changed. At this time, there are no known lifestyle
risk factors for ALL.
Being a survivor of an atomic bomb blast or nuclear reactor
accident has been linked to ALL.
There is some concern about very high-voltage power lines
as a risk factor for leukemia. The United States National
Cancer Institute (NCI) has several large studies going
on now to look into this question. So far, the studies
show either no increased risk or a very slightly increased
risk. Clearly, most cases of leukemia are not related
to power lines.
A small number of people are at greater risk of acute
leukemia because they have certain rare diseases or because
the have a certain virus (HTLV-1).
Can Acute Lymphocytic Leukemia Be
Prevented?
Most people who develop ALL do not have any of the above
risk factors. The cause of their leukemia remains unknown
at this time. Because the cause is not known, there is
no way to prevent most cases of ALL.
How Is Acute Lymphocytic Leukemia
Found?
At this time, there are no special tests that can find
acute leukemia early. The best course of action is to
report any symptoms to the doctor right away.
Leukemia can cause many signs and symptoms, some of them
very general in nature. Keep in mind that the symptoms
mentioned below are most often caused by something other
than cancer.
General symptoms of ALL can include weight loss, fever,
and loss of appetite.
Most symptoms of ALL are caused by a shortage of normal
blood cells, a result of the crowding out of normal blood
cell-producing bone marrow by leukemia cells. As a result,
the person doesn't have enough properly working red blood
cells, white blood cells, and platelets.
Anemia is a result of a shortage of red blood cells. Anemia
causes shortness of breath, fatigue, and a pale skin color.
Not having enough normal white blood cells can increase
the risk of infection. Although people with leukemia may
have very high white blood cell counts, the cells are
not normal and do not protect against infection very well.
Not having enough blood platelets can lead to bruising,
bleeding, frequent or severe nosebleeds, and bleeding
from the gums.
ALL can spread outside of the bone marrow to other organs.
If it spreads to the brain or spinal cord (central nervous
system), it can cause symptoms such as headaches, weakness,
seizures, vomiting, trouble keeping one's balance, and
blurred vision.
Some people have bone pain or joint pain caused by the
spread of cancer cells to the surface of the bone or into
the joint.
Leukemia can also cause swelling of the liver and spleen.
If the disease has spread to the lymph nodes, these nodes
may be swollen.
The T-cell type of ALL often involves the thymus, a gland
found in the center of the chest, near the heart. An enlarged
thymus can press on the nearby windpipe, causing coughing,
shortness of breath, or even suffocation. A large vein,
the superior vena cava (SVC) that carries blood from the
head and arms back to the heart, also passes next to the
thymus. If leukemia cells compress the SVC, swelling of
the head and arms (SVC syndrome) can result. This can
affect the brain and is life threatening. People with
SVC syndrome need treatment right away.
If Acute Lymphocytic Leukemia Is
Suspected
If there is reason to think that you might have leukemia,
the doctor will need to take samples of cells from your
blood and bone marrow to find out if the disease is really
present.
Bone marrow tests: In bone marrow aspiration,
a thin needle is used to draw up a small amount of liquid
bone marrow. During a bone marrow biopsy, a small cylinder
of bone and marrow (about ½ inch long) is removed
with a slightly larger needle.
Both samples are usually taken at the same time from the
back of the hipbone. The patient lies face down and the
area is cleaned with a special soap. Before the sample
is taken, the doctor injects an anesthetic into area near
the back of the hipbone to numb it. Then the doctor makes
a small cut in order to insert a needle. The needle is
moved through the bone with a twisting motion. Sometimes
the needle going into the bone is painful, but it only
lasts a short time. During aspiration, the sucking out
is often painful for a brief moment.
These tests are used to tell whether leukemia is present
and also, if you are having treatment, how well the disease
is responding.
Excisional lymph node biopsy: In this
procedure, an entire lymph node is removed. If the node
is near the skin's surface, a simple operation can be
done by numbing just the area around the node. But if
the node is inside the chest or abdomen, the patient will
need general anesthesia (the patient is asleep). This
test is only rarely needed for people with leukemia.
Spinal tap (lumbar puncture): In this
procedure, a small needle is placed into the spinal cavity
in the lower back to draw out some cerebrospinal fluid.
The fluid is examined for leukemia cells.
Lab tests: Doctors use a number of very
precise lab tests to diagnose and classify leukemia.
Blood cell counts and other blood tests: Changes in the
numbers of different blood cell types and how the cells
look under a microscope can suggest leukemia. Most people
with acute lymphocytic leukemia (ALL) have too many white
blood cells, not enough red cells, and not enough platelets.
Also, many of the white cells will be blasts, a type of
immature cell not normally found in circulating blood.
These cells don't work the way they should.
People already known to have leukemia will have tests
done to measure the amount of certain chemicals in the
blood. These tests do not tell if they have leukemia but
can help tell how well their kidneys and liver are working.
A doctor with special training in blood diseases looks
at all of the biopsy samples (bone marrow, lymph node
tissue, blood, and cerebrospinal fluid) under a microscope.
The doctor looks at the size and shape of the cells as
well as other features to classify the cells into specific
types. An important goal of this process is to see whether
the cells appear mature or not. The most immature cells
are called blasts. The number of blasts in the bone marrow
is important in telling if a person has leukemia. Having
at least 20% to 30% of blasts in the marrow is generally
the benchmark for a diagnosis of ALL.
Other special tests which look at blood, marrow, and even
DNA to help tell which type of leukemia a person has.
These are complex medical and chemical tests. Your doctor
can tell you which of these you might need.
Imaging studies: Imaging studies are
ways of producing pictures of the inside of the body.
Because leukemia does not usually form tumors, imaging
tests are not always helpful. Imaging studies might be
done in people with ALL, but they are done more often
to look for infections or other problems rather than for
the leukemia itself.
X-rays may be done to see if there is
a lung infection. The x-ray can also show enlarged lymph
nodes in the chest.
CT (computed tomography) scans are special
kinds of x-rays in which a beam moves around the body,
taking pictures from different angles. The pictures are
combined by a computer into an image of a slice of the
body. CT scans are helpful in looking at internal organs.
They can show pockets of infection, enlarged organs, and
any large collection of leukemia cells.
MRI (magnetic resonance imaging) is a
method that uses powerful magnets and radio waves to produce
detailed, computer-generated pictures of the body. MRI
scans are helpful in looking at the brain and spinal cord.
MRI scans take longer than CT scans. Also, you may be
placed inside a tube, which can feel confining.
Gallium scans and bone scans involve
injecting a radioactive chemical into the blood. The chemical
collects in areas of cancer or infection, where it can
be seen by a special camera. These tests are useful when
a person has bone pain that might be caused by either
infection or cancer involving bones.
Ultrasound uses sound waves to produce
images of internal organs. This test can tell solid from
fluid-filled masses. It can help to show whether the kidneys,
liver, or spleen are enlarged. This is an easy test to
have done. You simply lie on a table and a kind of wand
is moved over the part of your body being examined.
How is Acute Lymphocytic Leukemia
Classified?
Most types of cancer are assigned a numbered stage based
on the size of the tumor and how far it has spread. But
there is no need to stage leukemia in this way because
it already involves all the bone marrow and, in many cases,
it has also spread to other organs.
Several years ago, an international conference of doctors
who specialize in leukemia was held to decide on the best
system for classifying acute leukemia. They decided upon
3 subtypes for ALL.
For leukemia, lab tests focus on finding out the exact
type and subtype of leukemia, which in turn helps the
doctor predict which treatments will work best.
Certain features of the disease separate patients who
are likely to have a good response to treatment from those
likely to have a poor response. These are called prognostic
factors. These features include the patient's age, white
blood cell count, certain test results, and initial response
to chemotherapy.
While some patients might find detailed information about
subtypes and prognostic factors helpful, others may find
it a bit overwhelming. The American Cancer Society has
detailed information about these subtypes and prognostic
factors in a separate document ("Leukemia –
Acute Lymphocytic") available through our toll-free
number or on our Web site.
How Is Acute Lymphocytic Leukemia
Treated?
As noted before, acute lymphocytic leukemia is not a single
disease. It is really a group of diseases and people with
different subtypes vary in how they respond to treatment.
Treatment options are based on the subtype as well as
on the prognostic features.
Chemotherapy is the major treatment for ALL. Surgery and
radiation may be used in some cases.
Chemotherapy refers to the use of drugs to kill cancer
cells. Usually the drugs are given into a vein or by mouth.
Once the drugs enter the bloodstream, they spread throughout
the body. Chemotherapy for ALL involves the use of several
drugs given over a long period of time.
Side Effects of Chemotherapy
While chemotherapy drugs kill cancer cells, they can also
damage normal cells. This happens because they target
rapidly growing cells such as cancer cells but in the
process they also damage other fast growing cells.
The side effects of chemotherapy depend on the type and
dose of drugs given and the length of time they are taken.
These side effects might include:
• hair loss
• mouth sores
• higher risk of infection (due to low white blood cells)
• easy bruising or bleeding (due to low blood platelets)
• tiredness (due to low red blood cells)
• loss of appetite
• nausea
• vomiting
The side effects usually go away after treatment ends.
Be sure to talk to your doctor if you are having trouble
with side effects because there are often ways to manage
them during treatment. For example, there are drugs than
can be taken along with the chemotherapy to prevent or
reduce nausea and vomiting. Drugs known as growth factors
are sometimes given to keep blood counts higher and reduce
the chance of infection.
Other ways you can reduce the risk of infection are by
avoiding exposure to germs as much as possible and by
carefully washing your hands and not eating uncooked fruits
and vegetables. While in treatment you should also avoid
large crowds and people who are sick.
During and after treatment, you might also get antibiotics
as added protection. If your platelet counts are low,
you might get platelet transfusions to protect against
bleeding. Low red blood cell counts, causing shortness
of breath and tiredness, can be treated with drugs or
with transfusions.
Tumor lysis syndrome is a side effect
caused by the rapid breakdown of leukemia cells due to
treatment. When these cells die, they release substances
into the bloodstream that can affect the kidneys, heart,
and nervous system. Extra fluids or certain drugs that
help rid the body of these toxins can help prevent this
problem.
Finally, some people treated for ALL could later develop
AML (acute myeloid leukemia). Less often, people cured
of leukemia might later develop non-Hodgkin lymphomas
or other cancers.
Targeted Therapy
A newer drug called imatinib (Gleevec) has been used to
successfully treat chronic myeloid leukemia (CML). Clinical
trials are going on now to see if this drug will be helpful
in treating some people with ALL as well. Early reports
have shown a better outcome when imatinib was used. This
drug also seems to cause fewer side effects than other
chemotherapy drugs. Possible side effects include diarrhea,
nausea, muscle pain, and fatigue, but these are often
mild.
Monoclonal antibodies are large proteins
made in the lab. They attach to certain molecules on the
surface of leukemia cells. These antibodies have been
used to treat lymphomas. Researchers are now looking at
whether they might be useful in treating some patients
with ALL. Early results have been favorable, but it’s
still too early to know for sure.
Surgery
Surgery is not generally used to treat leukemia because
this is a disease of blood and bone marrow and it is not
possible cure it with surgery. But surgery may be used
to help deliver treatment. A plastic tube can be placed
into a large vein. The tube, called a venous access device,
allows chemotherapy drugs or other medicines to be given
and blood samples removed without the need for many needle
sticks. The patient will need to learn how to take care
of the device to prevent it from getting infected.
Radiation Therapy
Radiation therapy is the use of high energy x-rays to
kill cancer cells. It is sometimes used to treat leukemia
that has spread to the brain and spinal cord or to the
testicles.
Radiation to several parts of the body is often done before
a bone marrow or blood stem cell transplant (see below).
It is also used, though rarely, in an emergency to shrink
a mass if it is pressing on the windpipe. But more often
chemotherapy is used instead.
Bone Marrow or Peripheral Blood Stem Cell Transplantation
As noted earlier, chemotherapy can harm normal cells as
well as cancer cells. Stem cell transplantation (SCT)
offers a way for doctors to use high doses of chemotherapy.
Although the drugs destroy the patient's bone marrow,
transplanted stem cells can restore the bone marrow’s
ability to make blood. Transplants using the patient’s
own stem cells are sometimes used for people with acute
leukemia that is in remission.
The treatment works like this: stem cells for are collected
from the bone marrow, or from the bloodstream in a process
called apheresis. These stem cells can come from either
the patient or from a suitable donor. The stems cells
are frozen and stored.
Patients are then given very high doses of chemotherapy
to kill the cancer cells. They also receive total body
radiation to kill any remaining cancer cells. After treatment,
the stored stem cells are given to the patient as a blood
transfusion. Then the waiting period begins as the stem
cells settle in the patient's bone marrow and start to
grow and produce blood cells.
People who receive a donor's stem cells are given drugs
to prevent rejection as well as other medicines as needed
to prevent infections. Usually around 10 to 21 days after
the stem cells are given, they start making new white
blood cells. Then they begin making platelets, and finally,
red blood cells.
Patients having SCT have to be kept away from germs as
much as possible until their white blood cell count is
at a safe level. They are kept in the hospital until the
white cell count reaches a certain number, usually around
1,000. After they go home, they will be seen in the outpatient
clinic almost every day for several weeks.
Stem cell transplantation is still a fairly new and complex
treatment. If the doctors think that a person with leukemia
might be helped by this treatment, it is important that
it be done at a hospital where the staff has experience
with the procedure. Some transplant programs may not have
experience in certain transplants, especially those from
unrelated donors.
Stem cell transplantation is very expensive and requires
a long hospital stay. Because some insurance companies
see it as an experimental treatment, they might not pay
for it.
Side Effects of Stem Cell Transplantation
Side effects from stem cell transplantation can be divided
into early and long-term effects. The early side effects
are basically the same as those caused by any other type
of high-dose chemotherapy. But other side effects can
last for a long time, or they may not occur until years
after the transplant. These long-term side effects can
include the following:
• radiation damage to the lungs, causing shortness of
breath
• graft-versus-host disease (GVHD), which occurs only
in a donor transplant (see below)
• damage to the ovaries causing infertility and the loss
of menstrual periods
• damage to the thyroid gland that causes problems with
changing food into energy
• cataracts (damage to the eye that can affect vision)
• bone damage (if damage is severe, the patient will need
to have part of the bone and joint replaced.)
Graft-versus-host disease is the main problem of a donor
stem cell transplant. It happens when the immune system
of the patient is taken over by that of the donor. The
donor immune system then starts to attack the patient’s
other tissues and organs.
Symptoms can include severe skin rashes with itching and
severe diarrhea. The liver and lungs may also be damaged.
The patient may also become tired and have aching muscles.
If severe enough, the disease can be fatal. Drugs that
affect the immune system may be given to try to control
it. On the plus side, this disease also causes any remaining
leukemia cells to be killed by the donor immune system.
For ALL, chemotherapy treatments are given in the following
phases:
Remission induction: The purpose of the first phase is
to bring about a remission--the disappearance of the signs
and symptoms of the cancer. A remission may not be a cure.
Consolidation: The goal of this phase is to get rid of
leukemia cells from places where they can "hide."
This lasts from one to a few months.
Maintenance: Once the number of leukemia cells has been
reduced by the first 2 phases of treatment, this last
phase can begin. Maintenance, which usually consists of
lower doses of chemotherapy drugs, lasts about 2 years.
In general, about 8 out of 10 patients will have a complete
response to these treatments. That means that leukemia
can no longer be seen in their bone marrow. But about
half of these patients will have a relapse, so the overall
cure rate is around 30%.
Central nervous system treatment: Because ALL often spreads
to the coverings of the brain and spinal cord, patients
often receive chemotherapy in the spinal fluid or radiation
therapy of the head as a method of prevention.
Finally, some patients who are at high risk for relapse
(because of poor prognostic factors) may have a stem cell
transplant.
What if the Leukemia Doesn’t
Respond or Comes Back After Treatment?
If the leukemia comes back after treatment,
it will most often do so in the bone marrow and blood.
Once in a while, the brain or spinal fluid will be the
first place it returns.
If the leukemia had gone away and has now come back, it
may be possible to bring about another remission, although
most doctors think this remission will be only temporary.
In these cases most doctors will consider a stem cell
transplant.
If the leukemia keeps coming back or doesn't go away,
chemotherapy will finally not be very helpful. If a stem
cell transplant is not an option, entering a clinical
trial (see section on Clinical Trials) might be a good
idea.
If neither of these options is the right one, then it
may be time to focus on relieving symptoms. The doctor
may suggest more mild chemotherapy to slow the growth
of the leukemia. If there is pain, then it's important
to treat it with pain killing medicines. Sometimes medicines
or blood transfusions are needed to correct low blood
counts and tiredness. If depression is a problem, that
can be treated as well. Nausea and loss of appetite can
be helped by high-calorie food supplements and medicines.
Antibiotics may be needed to treat infection.
Clinical Trials
Studies of promising new treatments are known as clinical
trials. A clinical trial is done only when there is some
reason to believe that the new treatment may be of value
to the patient. Clinical trials are needed in order to
find new and better ways to treat cancer. Treatments used
in clinical trials are often found to have real benefits.
The main questions the researchers want to answer are:
• Is this treatment helpful?
• Does it work better than the one we're now using?
• What side effects does it cause?
• Do the benefits outweigh the side effects?
• Which patients are most likely to find this treatment
helpful?
Clinical trials are carried out in steps called phases.
Each phase is designed to answer certain questions
Phase I clinical trials look at the best
way to give a new treatment and how much of it can be
given safely. The main purpose of a phase I study is to
test the safety of the new drug.
Phase II clinical trials are designed
to see if the drug works. Patients are given the highest
dose that doesn't cause serious side effects and then
watched closely to see if there is an effect on the cancer.
Phase III clinical trials compare the
new treatment with standard treatment. Large numbers of
patients are divided into two groups. The control group
receives standard treatment and the other group receives
the new treatment. Everyone is closely watched to see
which treatment is more effective. The study is stopped
if the side effects are too severe or if one group has
much better results than the other.
If you are in a clinical trial, you will have a team of
experts watching your progress very carefully. However,
there are some risks. No one knows in advance if the treatment
will work or exactly what side effects will occur. That
is what the study is designed to find out. Keep in mind,
though, that even standard treatments have side effects.
Taking part in a clinical trial is completely up to you.
Even after joining a clinical trial, you are free to drop
out of the study at any time, for any reason. Taking part
in the study will not prevent you from getting other medical
care you may need.
Courtesy: www.cancer.org,
Please visit the website for further information
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