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 |
