Acute Myelocytic Leukemia
Definition
Acute myelocytic leukemia (AML) is an acute cancer that affects white blood cells, primarily those of the granulocyte or monocyte types.
Description
Acute myelogenous leukemia and acute nonlymphocytic leukemia (ANLL)are other names for AML and refer to the identical disease. The cells that make up blood are produced in the bone marrow and the lymph system. The bone marrow is the spongy tissue found in the large bones of the body. The lymph system includes the spleen (an organ in the upper abdomen), the thymus (a small organ beneath the breastbone), and the tonsils (an organ in the throat). In addition, the lymph vessels (tiny tubes that branch like blood vessels into all parts of the body) and lymph nodes (pea-shaped organs that are found along the network of lymph vessels) are also part of the lymph system. The lymph is a milky fluid that contains cells. Clusters of lymph nodes are found in the neck, underarm, pelvis, abdomen, and chest. The main types of cells found in the blood are the red blood cells (RBCs), which carry oxygen and other materials to all tissues of the body; white blood cells (WBCs), which fight infection; and the platelets, which play a part in the clotting of the blood. The white blood cells can be further subdivided into three main types: granulocytes, monocytes, and lymphocytes.
The granulocytes, as their name suggests, have particles (granules) inside them. These granules contain special proteins (enzymes) and several other substances that can break down chemicals and destroy microorganisms such as bacteria. Monocytes are the second type of white blood cell. They are also important in defending the body against pathogens. The lymphocytes form the third type of white blood cell.
The bone marrow makes stem cells, which are the precursors of the different blood cells. These stem cells mature through stages into either RBCs, WBCs, or platelets. In acute leukemias, the maturation process of the white blood cells is interrupted. The immature cells (or “blasts”) proliferate rapidly and begin to accumulate in various organs and tissues, thereby affecting their normal function. This uncontrolled proliferation of the immature cells in the bone marrow affects the production of the normal red blood cells and platelets as well. Acute leukemias are of two types: acute lymphocytic leukemia and acute myelogenous leukemia. Different types of white blood cells are involved in the two leukemias. In acute lymphocytic leukemia (ALL), it is the lymphocytes that become cancerous. AML is a cancer of the monocytes and/or granulocytes. The reason certain leukemias are now called acute is because of names received decades ago. Before the discovery of modern methods of cancer treatment, these were illnesses that progressed rapidly. In contrast, chronic leukemias were, in this period before newer methods had been invented, illnesses that progressed more slowly.
Demographics
Approximately 23 new cases of AML appear per
each million Americans each year. Men are somewhat
more likely to develop AML than are women. Approximately
29 new cases appear per every million males
while approximately 19 new cases appear per every million
females per year.
Older persons are considerably more likely to develop
AML. Approximately 13 people per million younger
than 65 years of age will develop AML. In contrast, 122
people per million older than 65 years of age will develop
the disease.
AML sometimes affects children. About 500 children
develop AML in the United States every year.
Approximately one in five of all children who develop
leukemia develop AML. The disease affects boys and
girls in roughly equal numbers. Children of all ethnic
groups may develop the disease. If one of two identical
twins develops AML, the chances are considerable that
the other twin will develop it as well.
Causes and symptoms
AML is neither contagious nor inherited. However,
people who suffer from certain genetic disorders, such as
Fanconi anemia, Klinefelter syndrome, Patau syndrome,
Bloom syndrome, and Down syndrome, are at
greater risk of developing AML than the general population.
A child with Down syndrome is roughly 14 times as
likely as the average child to develop leukemia.
Any person who has been exposed to radiation at high
doses is at heightened risk of developing AML, as are people
exposed to benzene, a chemical used in the manufacture
of plastics, rubber, medicines, and certain other chemicals.
Another group of people at increased risk for developing
AML are those who have been treated for cancer
with certain medicines, for example, chloramphenicol,
phenylbutazone, chloroquine, and methoxypsoralen.
The symptoms of AML are generally vague and
non-specific. A patient may experience all or some of the
following symptoms:
• weakness or chronic fatigue
• fever of unknown origin
• shortness of breath
• weight loss that is not due to dieting or exercise
• frequent bacterial or viral infections
• headaches
• skin rash
• non-specific bone pain
• easy bruising
• bleeding from gums or nose
• blood in urine or stools
• enlarged lymph nodes and/or spleen
• abdominal fullness
A small minority of patients with AML have a tumor
of leukemic cells at diagnosis. Such a tumor may appear
in the lung, breast, brain, uterus, ovary, stomach,
prostate, or certain other places in the body.
Some children with AML present to their doctor
with very few symptoms, while other children present
with severe symptoms. Anemia is usually present. The
symptoms of the anemia may include fatigue, dizziness,
headache, paleness of the skin, or, infrequently, congestive
heart failure. Easy bruising, bleeding gums, and
nosebleeds may be present, as may fever. There may be
swollen gums, bone pain or joint pain, or, rarely, an actual
tumor. Some infants with AML have skin disorders.
Diagnosis
Like all cancers, acute leukemias are best treated
when found early. There are no screening tests available.
A thorough diagnostic evaluation should be conducted.
This is important because the doctor must determine
more than whether or not AML is present. If it is suspected,
has it affected the general health of the patient? Is the
patient capable of undergoing rigorous treatment?
A doctor who suspects leukemia may start by
obtaining a thorough medical history. The doctor may
then conduct a very thorough physical examination to
look for enlarged lymph nodes in the neck, underarm,
and pelvic region. Swollen gums, enlarged liver or
spleen, bruises, or pinpoint red rashes all over the body
are among the signs of the disease. In addition, the physician
may examine the teeth and look for dental abscesses,
and may explore whether back pain is present.
Urine and blood tests may be ordered to check for
microscopic amounts of blood in the urine and to obtain
a complete differential blood count. This count will
give the numbers and percentages of the different cells
found in the blood. An abnormal blood test might suggest
leukemia. Patients suffering from AML may have
high leukocyte counts and typically have low counts of
both red blood cells and platelets. Many patients with
AML have low counts of all of the major components
of the blood. A microscopic exploration of the blood
will usually show that leukemic blast cells are present.
However, the diagnosis has to be confirmed by more
specific tests.
The doctor may perform a bone marrow aspiration
and biopsy to confirm the diagnosis of leukemia. Aspiration
involves the withdrawal of a liquid sample of marrow.
During the biopsy, a cylindrical piece of bone and
marrow is removed. The tissue is generally taken out of
the hipbone. These samples are sent to the laboratory for
examination. In addition to diagnosis, the aspiration and
biopsy may be repeated during the treatment phase of the
disease to see if the leukemia is responding to therapy.
A chest x ray is taken. Cardiac tests, including an
electrocardiogram, are conducted. The patient is examined
for possible infection. These diagnostic procedures
often disclose bleeding in the stomach or intestines, and
there may be bleeding in the lungs, brain, or eyes. Anemia
is often present and may be severe.
Cytogenetic studies, which examine the number and
shape of the chromosomes in the DNA of individual blast
cells, should be conducted in addition to the immunophenotyping
of cells of the bone marrow. This procedure
involves applying various stains to the marrow cells.
These stains help doctors identify some of the proteins
lying on the surface of the cells.
A spinal tap (lumbar puncture) is another procedure
the doctor may order to diagnose leukemia. In this
procedure, a small needle is inserted into the spinal cavity
in the lower back to withdraw some cerebrospinal
fluid and to look for leukemic cells.
Standard imaging tests such as x rays may be used to
check whether the leukemic cells have invaded other
areas of the body, such as the bones, chest, kidneys,
abdomen, or brain. Other tests, such as computed
tomography scans (CT scans), magnetic resonance
imaging (MRI), or gallium scans, are not typical for
AML but may also be performed.
Children with AML are given most of the same studies
used for adults.
Clinical staging, treatments, and prognosis
Unlike several other cancers, AML is not staged.
However, a classification system is used to separate different
forms of AML. One of the most important classification
systems, devised by a team of physicians, is
known as the French-American-British (FAB) Classification
System.
The goal of AML treatment is to achieve a complete
remission (CR). What is a complete remission? It is a measure
that indicates that the patient’s disease has gotten
markedly better in several ways. In general, it might be said
that CR is achieved once the body has regained its ability to
produce blood cells normally. At this point, the number of
blood cells of various types should return to normal ranges,
while none of the immature cells called leukemic blast cells
should be present in the blood or the marrow.
Chemotherapy is the use of drugs to kill cancer
cells. It is usually the treatment of choice and is used to
relieve symptoms and achieve long-term remission of the
disease. Generally, combination chemotherapy, in which
multiple drugs are used, is more efficient than using a
single drug for the treatment. Some drugs may be administered
intravenously through a vein in the arm; others
may be given by mouth in the form of pills. If the cancer
cells have invaded the brain, then chemotherapeutic
drugs may be put into the fluid that surrounds the brain
and spinal cord. This is known as intrathecal chemotherapy.
Chemotherapy should start soon after diagnosis.
Patients who are anemic or who have low platelet
counts should receive transfusions. These transfusions
should be sufficient to restore counts of various components
of the blood to adequate levels.
There are two phases of treatment for leukemia. The
first phase is called induction therapy. During this phase,
the main aim of treatment is to reduce the number of
leukemic cells as much as possible and induce a remission
in the patient. A variety of chemotherapy agents may
be used during the induction therapy portion of AML
treatment. The chemotherapy agent Ara-C (cytarabine)
is in 2001 often used in combination with either
daunorubicin or idarubicin (Idamycin). Other doctors
add etoposide to this combination of chemotherapy
agents. For older patients, Ara-C and mitoxantrone may
be used. Some patients benefit from receiving high doses
of chemotherapy drugs. As of 2001,patients who do not
achieve CR, as well as those who achieve CR but then
relapse, may be given mitoxantrone plus etoposide.
The second phase of treatment is initiated once CR is
achieved. This is called post-remission or consolidation
therapy. The goal of therapy now becomes killing any
remaining cells and maintaining the remission for as long as
possible. There are various ways of attempting to reach this
goal. One involves additional chemotherapy. Another
involves bone marrow transplantation (BMT), also called
stem cell transplant (SCT). Transplantation therapy has
been studied very thoroughly. It involves taking blood-making
cells, whether from the patient or from another person,
and infusing them into the patient following removal of the
diseased marrow, with either high doses of chemotherapy or
total body irradiation. These procedures are potentially very
effective because of the remarkable ability of these cells to
create a sustained replacement of the patient’s blood cells.
Other strategies may also be applied. Approaches used for
patients younger than 60 years of age may differ from those
used for patients of older ages.
Because leukemia cells can spread to all the organs
via the blood stream and the lymph vessels, surgery is
not considered an option for treating leukemias.
Children with AML also receive induction therapy.
Often two or three medicines are used in conjunction
with one another. After remission is achieved in a young
patient, postremission therapy is started. The type of
postremission therapy depends largely on the type of
AML the patient has. It may involve additional
chemotherapy or, alternatively, bone marrow transplantation.
Chemotherapy to the central nervous system (CNS)
is given to most children, since without it, roughly one in
five will develop CNS relapse. The CNS includes the
brain and spinal cord.
The prognosis of patients with AML varies. A
number of different matters should be examined before
the prognosis of any individual patient is assessed. The
most important of these is whether or not the patient
attains a complete remission (CR). The most important
consideration in terms of whether a patient is likely to
achieve CR is the patient’s age. However, it may be
that chronological age is not what really matters.
Rather, to a large extent, what is truly significant is the
patient’s ability to survive the difficulties associated
with induction therapy. For example, the patient who
has some other disease in addition to AML may have a
more difficult time with the rigors of the therapy. Yet, it
is also true that older patients are more likely to have
AML that expresses certain characteristics associated
with poorer outcomes.
Other factors also affect the patient’s prognosis. For
example, in the tests performed during diagnosis, the
chromosomes of cells are examined. Some chromosomal
findings are associated with a good prognosis. Others are
only mildly good, while still others indicate the patient is
less likely to achieve CR.
Other factors that may provide physicians with hints
as to the patient’s prognosis include: how long symptoms
were present before the illness was diagnosed, and how
quickly immature blast cells disappear after treatment is
started.
Coping with cancer treatment
One of the most important aspects of treatment is
guaranteeing that the patient will have the supportive
care needed to come through the treatment period with
physical and emotional strength intact. Part of what this
means is that AML should be treated in major cancer
centers, because only these centers have the expertise
necessary to provide not only the right medicine but also
the accompaniments of good treatment.
One way physicians help AML patients cope with
treatment is to guarantee that adequate blood bank support
is available. Many patients require platelet transfusions.
One of the great dangers to patients during induction
treatment and other steps of treatment is the threat
of serious infectious disease. These patients have weakened
blood components and are therefore more susceptible
to infectious illness than the average person is. The
leading cause of death for patients receiving induction
treatment and chemotherapy following remission is
infectious illness.
To help build the patient’s white cell count, doctors
may prescribe growth factors. These encourage the body
to produce certain types of blood cells. The types of
growth factors prescribed most frequently are granulocyte-
colony stimulating factor (G-CSF) and granulocytemacrophage
colony stimulating factor (GM-CSF).
The psychological aspects of cancer treatment are a
major concern. Patients should ask their physician about
local support groups and survivor networks that can help
with the stresses associated with this disease.
Prevention
High doses of radiation and exposure to the chemical
benzene (used in the manufacture of plastics, rubber,
and medicines) are strong risk factors. With the exception
of people with such rare genetic conditions as Fanconi
anemia, Klinefelter syndrome, Patau syndrome,
Bloom syndrome, and Down syndrome, there is no
known genetic predisposition to AML.
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