Definition

By Mayo Clinic Staff

Leukemia is cancer of the body's blood-forming tissues, including the bone marrow and the
lymphatic system.

Many types of leukemia exist. Some forms of leukemia are more common in children. Other
forms of leukemia occur mostly in adults.

Leukemia usually involves the white blood cells. Your white blood cells are potent infection
fighters they normally grow and divide in an orderly way, as your body needs them. But in
people with leukemia, the bone marrow produces abnormal white blood cells, which don't
function properly.

Treatment for leukemia can be complex depending on the type of leukemia and other factors.
But there are strategies and resources that can help to make your treatment successful.

Symptoms
By Mayo Clinic Staff

Multimedia

Petechiae

Leukemia symptoms vary, depending on the type of leukemia. Common leukemia signs and
symptoms include:

Fever or chills
Persistent fatigue, weakness
Frequent or severe infections
Losing weight without trying
Swollen lymph nodes, enlarged liver or spleen
Easy bleeding or bruising
Recurrent nosebleeds
Tiny red spots in your skin (petechiae)
Excessive sweating, especially at night
Bone pain or tenderness
When to see a doctor

Make an appointment with your doctor if you have any persistent signs or symptoms that worry
you.

Leukemia symptoms are often vague and not specific. You may overlook early leukemia
symptoms because they may resemble symptoms of the flu and other common illnesses.

Rarely, leukemia may be discovered during blood tests for some other condition.

Causes
By Mayo Clinic Staff

Multimedia

Parts of the immune system

Scientists don't understand the exact causes of leukemia. It seems to develop from a combination
of genetic and environmental factors.

How leukemia forms

In general, leukemia is thought to occur when some blood cells acquire mutations in their DNA
the instructions inside each cell that guide its action. There may be other changes in the cells
that have yet to be fully understood could contribute to leukemia.

Certain abnormalities cause the cell to grow and divide more rapidly and to continue living when
normal cells would die. Over time, these abnormal cells can crowd out healthy blood cells in the
bone marrow, leading to fewer healthy white blood cells, red blood cells and platelets, causing
the signs and symptoms of leukemia.

How leukemia is classified

Doctors classify leukemia based on its speed of progression and the type of cells involved.

The first type of classification is by how fast the leukemia progresses:

 Acute leukemia. In acute leukemia, the abnormal blood cells are immature blood cells (blasts).
They can't carry out their normal functions, and they multiply rapidly, so the disease worsens
quickly. Acute leukemia requires aggressive, timely treatment.
Chronic leukemia. There are many types of chronic leukemias. Some produce too many cells
and some cause too few cells to be produced. Chronic leukemia involves more mature blood
cells. These blood cells replicate or accumulate more slowly and can function normally for a
period of time. Some forms of chronic leukemia initially produce no early symptoms and can go
unnoticed or undiagnosed for years.

The second type of classification is by type of white blood cell affected:

Lymphocytic leukemia. This type of leukemia affects the lymphoid cells (lymphocytes), which
form lymphoid or lymphatic tissue. Lymphatic tissue makes up your immune system.
Myelogenous (my-uh-LOHJ-uh-nus) leukemia. This type of leukemia affects the myeloid cells.
Myeloid cells give rise to red blood cells, white blood cells and platelet-producing cells.

Types of leukemia

The major types of leukemia are:

Acute lymphocytic leukemia (ALL). This is the most common type of leukemia in young children.
ALL can also occur in adults.
Acute myelogenous leukemia (AML). AML is a common type of leukemia. It occurs in children
and adults. AML is the most common type of acute leukemia in adults.
Chronic lymphocytic leukemia (CLL). With CLL, the most common chronic adult leukemia, you
may feel well for years without needing treatment.
Chronic myelogenous leukemia (CML). This type of leukemia mainly affects adults. A person
with CML may have few or no symptoms for months or years before entering a phase in which
the leukemia cells grow more quickly.
Other types. Other, rarer types of leukemia exist, including hairy cell leukemia, myelodysplastic
syndromes and myeloproliferative disorders.

Risk factors
By Mayo Clinic Staff

Factors that may increase your risk of developing some types of leukemia include:

Previous cancer treatment. People who've had certain types of chemotherapy and
radiation therapy for other cancers have an increased risk of developing certain types of
leukemia.
Genetic disorders. Genetic abnormalities seem to play a role in the development of
leukemia. Certain genetic disorders, such as Down syndrome, are associated with an
increased risk of leukemia.
 Exposure to certain chemicals. Exposure to certain chemicals, such as benzene
which is found in gasoline and is used by the chemical industry also is linked to an
increased risk of some kinds of leukemia.
Smoking. Smoking cigarettes increases the risk of acute myelogenous leukemia.
Family history of leukemia. If members of your family have been diagnosed with
leukemia, your risk for the disease may be increased.

However, most people with known risk factors don't get leukemia. And many people with
leukemia have none of these risk factors.

Tests and diagnosis

Doctors may find chronic leukemia in a routine blood test, before symptoms begin. If this
happens, or if you have signs or symptoms that suggest leukemia, you may undergo the
following diagnostic exams:

Physical exam. Your doctor will look for physical signs of leukemia, such as pale skin from
anemia, swelling of your lymph nodes, and enlargement of your liver and spleen.
Blood tests. By looking at a sample of your blood, your doctor can determine if you have
abnormal levels of white blood cells or platelets which may suggest leukemia.
Bone marrow test. Your doctor may recommend a procedure to remove a sample of bone
marrow from your hipbone. The bone marrow is removed using a long, thin needle. The sample
is sent to a laboratory to look for leukemia cells. Specialized tests of your leukemia cells may
reveal certain characteristics that are used to determine your treatment options.

You may undergo additional tests to confirm the diagnosis and to determine the type of leukemia
and its extent in your body. Certain types of leukemia are classified into stages, indicating the
severity of the disease. Your leukemia's stage helps your doctor determine a treatment plan.

Treatments and drugs

Treatment for your leukemia depends on many factors. Your doctor determines your leukemia
treatment options based on your age and overall health, the type of leukemia you have, and
whether it has spread to other parts of your body.

Common treatments used to fight leukemia include:

Chemotherapy. Chemotherapy is the major form of treatment for leukemia. This drug
treatment uses chemicals to kill leukemia cells.

Depending on the type of leukemia you have, you may receive a single drug or a
combination of drugs. These drugs may come in a pill form, or they may be injected
directly into a vein.

Biological therapy. Biological therapy works by using treatments that help your immune system
recognize and attack leukemia cells.
 Targeted therapy. Targeted therapy uses drugs that attack specific vulnerabilities within
your cancer cells.

For example, the drug imatinib (Gleevec) stops the action of a protein within the
leukemia cells of people with chronic myelogenous leukemia. This can help control the
disease.

Radiation therapy. Radiation therapy uses X-rays or other high-energy beams to

damage leukemia cells and stop their growth. During radiation therapy, you lie on a table
while a large machine moves around you, directing the radiation to precise points on your
body.

You may receive radiation in one specific area of your body where there is a collection of
leukemia cells, or you may receive radiation over your whole body. Radiation therapy
may be used to prepare for a stem cell transplant.

Stem cell transplant. A stem cell transplant is a procedure to replace your diseased bone
marrow with healthy bone marrow.

Before a stem cell transplant, you receive high doses of chemotherapy or radiation
therapy to destroy your diseased bone marrow. Then you receive an infusion of blood-
forming stem cells that help to rebuild your bone marrow.

You may receive stem cells from a donor, or in some cases you may be able to use your
own stem cells. A stem cell transplant is very similar to a bone marrow transplant.

Acute myeloid leukemia (AML)

Is a cancer of the bone marrow and the blood
Progresses rapidly without treatment
Affects mostly cells that aren't fully developed- these cells can't carry out their normal
functions
Can be a difficult disease to treat. Researchers are studying new approaches to AML
therapy in clinical trials.

As a result, the number of healthy blood cells (red cells, white cells and platelets) is usually
lower than normal.

Anemia is a condition when there is a low number of red cells in the blood which can
cause fatigue and shortness of breath.
 Neutropenia is a condition when there is a low number of white cells so that the immune
system can't effectively guard against infection due to a lack of neutrophils (a type of
white cell).
Thrombocytopenia is a condition when there is a low number of platelets which can
cause bleeding and easy bruising with no apparent cause.
Low numbers of all three blood cell counts is called pancytopenia.

Risk Factors
For most people who have AML, there are no obvious reasons (risk factors) why they developed
the disease. You cannot catch AML from someone else.

Researchers have identified potential risk factors, including:

Repeated exposure to the chemical benzene, which damages the DNA of normal
marrow cells. According to the Agency for Toxic Substances and Disease Registry, half
of the total national personal exposure to benzene comes from cigarette smoke even
though petroleum products contribute to the majority of benzene in the atmosphere.
Benzene is also found in certain industrial settings; however, the strict regulation of its
use has decreased benzene exposure in the workplace.
Certain genetic disorders such as Down syndrome, Fanconi's anemia, Shwachman
syndrome and Diamond-Blackfan syndrome
Past chemotherapy or radiation treatments for other cancers.
Progression of other blood cancers or disorders, polycythemia vera, primary
myelofibrosis, essential thrombocythemia and myelodysplastic syndromes (MDS).

Source: Acute Myeloid Leukemia. Reviewed by Frederick Appelbaum, MD.

The signs and symptoms of acute myeloid leukemia (AML) are common to other, less serious
illnesses. However, if you're troubled by any of the following symptoms, see your doctor:

It is common for people with AML to feel a loss of well-being because of the underproduction of
normal bone marrow cells. The person may tire more easily and have shortness of breath during
normal physical activities. People with AML may also have

A pale complexion from anemia

Signs of bleeding caused by a very low platelet count, including
o Black-and-blue marks or bruises occurring for no reason or because of a
o minor injury
o The appearance of pinhead-sized red spots on the skin, called petechiae
o Prolonged bleeding from minor cuts
Mild fever
Swollen gums
Frequent minor infections
Loss of appetite and weight loss
Discomfort in bones or joints
 Enlarged spleen
Enlarged liver.

In addition to the signs and symptoms above, you may experience these conditions, which can be
dangerous without treatment:

Bleeding in the brain or a lung

Infection, especially if your body produces too few white cells known as neutrophils
Myeloid sarcoma, when a mass of AML cells can form a tumor elsewhere in the body

Acute Lymphoblastic Leukemia

Acute Myeloid Leukemia
o Signs and Symptoms
o Diagnosis
o Treatment
o Childhood AML
Chronic Lymphocytic Leukemia
Chronic Myeloid Leukemia
Hairy Cell Leukemia
Chronic Myelomonocytic Leukemia
Juvenile Myelomonocytic Leukemia
Large Granular Lymphocytic Leukemia
Blastic Plasmacytoid Dendritic Cell Neoplasm

An accurate diagnosis of the type of leukemia is important. The exact diagnosis helps the doctor
to

Estimate how the disease will progress

Determine the appropriate treatment.

Diagnosing acute myeloid leukemia (AML) and your AML subtype usually involves a series of
tests. Some of these tests may be repeated during and after therapy to measure the effects of
treatment.

Tests Your Doctor May Use to Diagnose AML

Blood and Bone Marrow Tests

Blood and bone marrow tests are used to diagnose AML and the AML subtype. A change in the
number and appearance of blood cells helps to make the diagnosis. AML cells look similar to
normal immature white cells. However, their development is incomplete.

Blood Tests
Blood samples are generally taken from a vein in the patients arm. Your blood is sent to a lab
for:

A complete blood count (CBC), which counts the number of red cells, white cells and platelets in
your blood. Usually, patients with AML have lower-than-expected numbers of red blood cells
and platelets.
A peripheral blood smear, which shows the presence of leukemic blast cells (myeloblasts). A
person with AML usually has too many leukemic blast cells in the blood. These cells do not
function like normal cells.

Bone Marrow Tests

Samples of marrow cells are obtained by bone marrow aspiration and biopsy. Bone marrow
testing involves two steps usually performed at the same time in a doctor's office or a hospital:

A bone marrow aspiration to remove a liquid marrow sample

A bone marrow biopsy to remove a small amount of bone filled with marrow

Both samples are examined under a microscope to look for chromosomal and other cell changes.

Other Tests

Karyotyping and cytogenetic analysis are processes used to identify certain changes in
chromosomes and genes. A laboratory test called polymerase chain reaction (PCR) may be
done, in which cells in a sample of blood or marrow are studied to look for certain changes in the
structure or function of genes, such as FLT3 and NPM1.

Diagnosing AML
In addition to looking at the number and appearance of the cells in the blood samples, your
doctor will also order other tests to

Confirm the diagnosis

Identify the AML subtype
Develop a treatment plan.

Your doctor will work with a hematopathologist to confirm the diagnosis. A hematopathologist
is a specialist who studies blood cell diseases by looking at samples of blood and marrow cells
and other tissues.

The diagnosis of AML is confirmed by identifying:

Leukemic blast cells in bone marrow samples

The percentage of blast cells. Blasts are normally 1 to 5 percent of marrow cells. Having at least
20 percent blasts is generally required for a diagnosis of AML. But AML can also be diagnosed if
 the blasts have a chromosome change that occurs in a specific type of AML, even if the blast
percentage is less than 20 percent.
Characteristic markers (antigens) on the surface of blast cells, such as CD13 or CD33 (CD is an
abbreviation for cluster designation).
Cells based on the types of markers (antigens) on the cell surface, using a process called
immunophenotyping. Flow cytometry is the name of one test that may be used to do
immunophenotyping.

Chromosome and Gene Abnormalities

About 60 percent of people with AML have abnormal chromosomes (number and/or structure).
These may affect a patients response to treatment. Certain changes to chromosomes and genes
can provide important information for risk assessment and treatment planning.

AML patients with normal chromosomes may have genetic mutations. Your doctor will perform
a molecular analysis on your cells to identify genetic changes.

Access the booklet Acute Myeloid Leukemia for a full listing of chromosome and gene
abnormalities.

It's important to know your AML subtype because it plays a large part in determining the type of
treatment you'll receive. Doctors often use one of two systems to classify subtypes:

French, American, British (FAB) system

World Health Organization (WHO) classification system

French, American, British (FAB) System

AML cells may have features of red cells, platelets or white cells in addition to myeloblasts or
promyelocytes. AML subtypes M0 through M5 start in early white cells, subtype M6 starts in
early red cells while subtype M7 starts in early platelet cells.

AML subtypes based on the FAB classification

FAB Subtype Description
M0 AML minimally differentiated
M1 AML with minimal maturation
M2 AML with maturation
M3 Acute promyelocytic leukemia
M4 Acute myelomonocytic leukemia
M4 eos Acute myelomonocytic leukemia with eosinophilia
M5 Acute monocytic leukemia
M6 Acute erythroid leukemia
M7 Acute megakaryoblastic leukemia
World Health Organization (WHO) Classification System
In 1999, the World Health Organization (WHO) developed a new classification system, which
incorporated information about cytogenetics to determine prognostic subgroups that may help
define treatment strategies.

AML Subtypes Based on the WHO Classification

AML with recurrent genetic abnormalities

AML with translocation between chromosomes 8 and 21

AML with translocation or inversion in chromosome 16
AML with translocation between chromosomes 9 and 11
APL (M3) with translocation between chromosomes 15 and 17
AML with translocation between chromosomes 6 and 9
{AML with translocation or inversion in chromosome 3

AML (megakaryoblastic) with a translocation between chromosomes 1 and 22

AML with myelodysplasia-related changes
AML related to previous chemotherapy or radiation

Alkylating agent-related AML

Topoisomerase II inhibitor-related AML

AML not otherwise categorized

(does not fall into above categories - similar to FAB classification)

AML minimally differentiated (M0)

AML with minimal maturation (M1)
AML with maturation (M2)
Acute myelomonocytic leukemia (M4)
Acute monocytic leukemia (M5)
Acute erythroid leukemia (M6)
Acute megakaryoblastic leukemia (M7)
Acute basophilic leukemia
Acute panmyelosis with fibrosis

Myeloid Sarcoma (also known as granulocytic sarcoma, chloroma or extramedullary

myeloblastoma)
Undifferentiated and biphenotypic acute leukemias (also known as mixed phenotype acute
leukemias)

It's important that your doctor is experienced in treating patients with acute leukemia or has
access to an acute myeloid leukemia (AML) specialist.
Types of AML Treatment
Doctors use several types of treatment for adults with AML, some at different stages. Click on
the links below to read more about each type of treatment.

Chemotherapy or other drug therapies. Chemotherapy is the use of potent drugs or

chemicals, often in combinations or intervals, to kill or damage cancer cells. Some
different anticancer drugs are used to treat acute promyelocytic leukemia (subtype M3).
Stem cell transplantation. This may be used with a second phase of chemotherapy.
Clinical trials. Clinical trials can involve therapy with new drugs and new drug
combinations or new approaches to stem cell transplantation.

Finding the Best Treatment Approach

Most AML patients, particularly patients with high white cell counts, need treatment soon after
diagnosis because of the disease's rapid progression. The initial goal of treatment usually is to get
the patient into remission. The long-term goal is to cure the disease.

A number of factors affect the choice and outcome of treatment, including:

Your AML subtype

The results of cytogenetic analysis
Whether you have received chemotherapy in the past to treat another type of cancer
Whether you have had myelodysplastic syndrome (MDS) or another blood cancer
Whether the AML is in your central nervous system
Whether your AML has not responded to treatment or has relapsed
The presence of systemic infection at diagnosis
Your age and general health.

As you develop a treatment plan with your doctor, be sure to discuss:

The results you can expect from treatment

The possibility of participating in a clinical trial, where you'll have access to advanced
medical treatment that may be more beneficial to you than standard treatment
Potential side effects, including long-term and late effects

You may find it helpful to bring a loved one with you to your doctor's visits for support, to take
notes and ask follow-up questions. It's a good idea to prepare questions you'd like to ask when
you visit your doctor. You can also record your conversations with your doctor and listen more
closely when you get home.

Click here to download lists of suggested questions to ask your healthcare providers.
Other Treatment Considerations
Age 60 or older, patient performance status, other health issues and AML risk
factors are all considered in developing your treatment plan, which may vary from
standard approaches. For instance, your body may not be able to tolerate toxic
chemotherapy drugs or you may have other ailments that are more common as you age.
These factors, among others, may make deciding on a treatment more complicated.
If your child is being treated for AML, therapy may differ slightly from that of the
average adult's therapy. See Childhood AML.
If your cancer has returned (relapsed) or it's still present after you finish standard
therapy (refractory leukemia), you may have a different treatment approach than the
first time around. See Refractory and Relapsed AML.

Acute myeloid leukemia (AML) is often treated in two phases, induction therapy and
postremission (consolidation) therapy.

What is Chemotherapy?
Chemotherapy is the use of potent drugs or chemicals, often in combinations or intervals, to kill
or damage cancer cells.
Chemotherapy can be hard on the body: The drugs toxicity can also damage or kill healthy cells
and cause side effects.
Everyone experiences side effects differently.

AML treatment is generally done in two phases (cycles):

Induction therapy
Postremission (consolidation) therapy
o Central nervous system prophylaxis

Treatment for patients with acute promyelocytic leukemia (APL), the M3 subtype of AML,
differs from other AML treatments. Click here to read about treatment for APL.

Treatment for patients with the FLT3 mutation may receive a different treatment combination.
Click here to read more.

Induction Therapy
The first phase of your treatment is induction therapy. Its goal is to "induce" (bring on) remission
(when no evidence of the disease is left). Specifically, induction therapy for AML attempts to:

Kill as many AML cells as possible with chemotherapy

Get healthy blood cell counts back to normal
 Get rid of all signs of the disease for an extended time

What type of treatment is used for AML induction therapy?

Doctors commonly combine two or more chemotherapy drugs to treat AML. Each type of drug
works in a different way to kill the cancerous cells. Combining drug types can strengthen their
effectiveness.
Most AML patients are treated with a combination of an anthracycline (such as daunorubicin
[Cerubidine], doxorubicin [Adriamycin PFS, Adriamycin] or idarubicin [Idamycin]) and
cytarabine (also called cytosine arabinoside or ara-C [Cytosar-U]).
Other drugs may be added or substituted for higher-risk, refractory or relapsed patients.

How are these drugs administered?

These drugs are administered through a catheter (a thin, flexible tube or intravenous line, which
is surgically placed in a vein, normally in the upper chest). The anthracycline is usually given in
the first 3 days of treatment. The cytarabine is started at the same time but is given for 7 to 10
days. This treatment is called 7 plus 3.

Where is the treatment done?

Induction therapy happens in the hospital, usually over 4-6 weeks. You may have to go through
several rounds of induction therapy before you go into remission. Usually the same drugs are
used for more rounds of treatment.

More Information

For a list of standard drugs and drugs under clinical study to treat AML, download or order The
Leukemia and Lymphoma Society's free booklet, Acute Myeloid Leukemia.
For information about the drugs mentioned on this page, visit Drug Listings.

Postremission Therapy
After induction therapy is complete and the patient is in remission, there will be another phase of
treatment is needed called postremission therapy, or consolidation therapy. This second
phase of treatment is used to destroy any stray AML cells not found by blood or marrow tests.
Without postremission therapy, the AML will likely return.

What type of treatment is used for AML postremission therapy?

Postremission therapy consists of additional intensive chemotherapy after remission has been
achieved, with or without autologous or allogeneic stem cell transplantation. If stem cell
 transplantation is not used, the treatment will generally consist of four cycles of chemotherapy.
For best results, intensive chemotherapy is given with high doses of cytarabine or other drugs.

Where is the treatment done?

Postremission therapy happens in the hospital and the length of stay depends on the treatment
and other factors.

Central Nervous System (CNS) Prophylaxis

CNS prophylaxis is a postremission treatment used to prevent central nervous system (CNS)
AML.

What is central nervous system (CNS) AML?

CNS AML, or meningeal leukemia, is when AML spreads to the meninges (the covering of the
spinal cord and brain).
CNS AML has a tendency to occur in patients with acute lymphoblastic leukemia and acute
monocytic leukemia
It is not common for CNS AML to be present at the time of initial AML diagnosis, and it more
commonly occurs in the form of relapse (the cancer returns after the patient is in remission).

Who is treated with central nervous system (CNS) prophylaxis?

Preventative therapy is usually not indicated for CNS AML but examination of the spinal fluid
after remission should be considered for some patients.

What type of treatment is used for CNS prophylaxis?

Chemotherapy drugs are injected into the spinal fluid (fluid that surrounds the spinal cord and
brain), using a treatment called intrathecal therapy.

Your doctor may recommend an allogeneic stem cell transplantation or an autologous stem cell
transplantation to treat your acute myeloid leukemia (AML). Stem cell transplantation isn't an
option for everyone, especially because of the high, sometimes life-threatening risks associated
with it. The question of which patients are likely to benefit from transplantation after their first
complete remission is under study in clinical trials.

Studies show that allogeneic stem cell transplantation may benefit high-risk and intermediate-
risk patients who are younger than 60 and have a sibling match. Treating with a reduced-
intensity transplant has shown some benefit for healthier older patients, up to age 75. There does
not seem to be any clear advantage for patients considered favorable or chemo-sensitive.
Autologous transplant is being used in some centers as an alternative to multiple cycles of
chemotherapy.
Allogeneic Stem Cell Transplantation
Allogeneic stem cell transplantation involves transferring stem cells from a healthy person (the
donor) to the patient. The procedure follows high-intensity chemotherapy, potent drugs that must
be toxic enough to kill leukemic cells. Unfortunately, the drugs also take aim at normal stem
cells in the bone marrow.

The main reasons for doing an allogeneic stem cell transplant are:

To start a new supply of red cells, white cells and platelets with help from the transplanted
donor stem cells
To give strong doses of chemotherapy to kill AML cells

The decision to do a stem cell transplant depends on:

The availability of a matched donor

Your response to oral drug therapy
Your understanding of the transplant's benefits and risks

Allogeneic stem cell transplantation is used to treat certain AML patients. It is a curative
treatment option for some AML patients in first remission. Allogeneic transplantation is
associated with a higher rate of side effects and mortality than autologous transplant. However, it
may be considered for patients with higher-risk AML, based on cytogenetic and molecular test
results. The decision to perform an allogeneic transplant also depends on the age of the patient
and the patients (or his or her familys) understanding of the potential benefits and risks. The
upper age limit for transplantation varies by treatment center; many centers use age 60 or 65
years for allogeneic transplantation and 70 or 75 years for reduced-intensity allogeneic
transplantation.

Reduced-Intensity Allogeneic Stem Cell Transplantation

Reduced-intensity allogeneic stem cell transplantation may be a treatment option for patients
who are too old or who may have other medical conditions that prevent them from having a
standard allogeneic stem cell transplant. The conditioning therapy used for a reduced-intensity
transplant is of lower intensity than that for a standard stem cell transplant; it does not
completely inactivate the patients immune system or treat the AML as intensively. Thus, if a
suitable donor is available, patients up to age 75 may benefit from this form of treatment.

Graft Versus Host Disease

A serious risk of allogeneic and reduced-intensity allogenic stem cell transplantation is graft
versus host disease (GVHD), which develops if the donor's immune cells attack your normal
tissue. GVHD's effects can range from minor to life threatening.
Autologous Stem Cell Transplantation
Autologous stem cell transplantation involves "harvesting," or retrieving, noncancerous stem
cells from the patients own body and freezing them. The cells are returned to the patients body
after receiving intensive chemotherapy. The procedure is only appropriate for certain patients.

The question of which patients are likely to benefit from transplantation after their first complete
remission is under study in clinical trials. The decision to do a stem cell transplant depends on
whether the patients AML is favorable risk, intermediate risk or high risk. The doctor also
considers:

The patients overall health

The chances that chemotherapy alone will cure the AML
The type of abnormal changes to the chromosomes and cells
The availability of a matched donor, if necessary
The patients understanding of the benefits and risks of transplant

Autologous transplantation is relatively safe for many patients, including older patients. For
some AML patients who do not have an HLA-matched stem cell donor, therapy can be further
intensified with very-high-dose chemotherapy followed by an autologous transplant.

Taking part in a clinical trial may be the best treatment choice for some acute myeloid leukemia
(AML) patients. Clinical trials are under way for patients at every treatment stage and for
patients in remission. Today's standard treatments for cancer are based on earlier clinical trials.
The Leukemia & Lymphoma Society continues to invest funds in AML research.

Click here to read more about clinical trials.

Current AML Research and Clinical Trials

Epigenetics is based on the idea that certain genes become silenced (or turned off),
which contributes to causing or maintaining cancer. Drugs that can reverse the silencing
process are being studied in clinical trials, either alone or in combination with other
drugs. Two gene-silencing processes scientists are trying to reverse include:
Methylation. Researchers are investigating two drugs that block methylation: azacitidine
(Vidaza) and decitabine (Dacogen). These hypomethylating agents are FDA approved
in the treatment of MDS. Both are being studied as single agents or in combination with
other drugs to treat newly diagnosed and relapsed/ refractory AML.
Histone deacetylation inhibition. Histone deacetylase inhibitors under study in clinical
trials include valproic acid, suberoylanilide hydroxamic acid (SAHA) and entinostat.
These drugs are being studied in combination with azacitidine or decitabine.
Sapacitabine, a nucleoside analog, has shown promising results in trials for the treatment
of older patients with AML.
 Clofarabine, a purine analog, related to cladribine has shown results as a single agent
and has also shown improved rates of remission in studies, when combined with low-
dose cytarabine in the treatment of older AML patients.
CPX-351 is a liposomal carrier (containing cytarabine and daunorubicin) and is being
studied in the treatment of relapsed AML patients.
Gemtuzumab ozogamicin is an antibody-drug conjugate that pairs the antitumor
antibiotic calicheamicin to an anti-CD33 antibody. This drug was FDA approved in 2000
based on its success treating older patients with relapsed AML but was later taken off the
market when studies indicated it did not offer long-term benefits. It is once again under
study as it has shown results in selected patients.
Vaccine therapy that will boost the immune reaction against AML cells is another
avenue of research. For instance, in one vaccine study, certain types of white blood cells
are removed and exposed to a protein found on many AML cells, called Wilms tumor 1
protein or WT1. These cells are then reinfused to the patient and help other immune cells
attach the leukemia cells. An early study of this vaccine has shown promising results but
more research is needed.
CAR T-cell therapy removes T cells from the patients blood and modifies them in the
lab so that they have specific substances known as chimeric antigen receptors (CARS)
that will help them attach to leukemia cells. Then, the cells are infused back into the
patient where they can target the leukemia cells. This technique has shown very
promising clinical trial results in the treatment of certain types of lymphocytic leukemias
and CAR T-cell therapy is now being studied for use in AML treatment.
Another concept called differentiation therapy involves studying the use of all-trans
retinoic acid (ATRA), which is approved to treat APL, and some types of histone
deacetylase inhibitor drugs to promote the growth and differentiation of immature
leukemic blast cells.

Both cancer therapy and acute myeloid leukemia (AML) can sometimes produce side effects. For
most patients, side effects are temporary and subside once the body adjusts to therapy or when
therapy is completed. For other patients, side effects can be more severe, sometimes requiring
hospitalization.

Before you undergo treatment, talk with your doctor about potential side effects. Drugs and other
therapies can prevent or manage many side effects.

Common Side Effects

Low blood cell counts. AML decreases the production of normal blood cells. In addition,
chemotherapy is toxic to both normal blood cells and AML cells. The normal blood cells
are eliminated from the marrow along with AML cells. For the patient, this results in a
severe deficiency in
o Red cells (anemia)
o Platelets (thrombocytopenia)
o White cells called neutrophils and monocytes (neutropenia and
monocytopenia).
Transfusion of red cells and platelets is almost always needed for a period of several weeks
during treatment. After that, the blood cell counts usually return toward normal.

Infection. During treatment for AML, the deficiency of neutrophils and monocytes (types
of white cells) can lead to infection. The risk of infection may be increased because
chemotherapy damages the lining of the mouth and intestines, making it easier for
bacteria to enter the blood. When the white cell count is low and infection risk is
increased, antibiotics are given to prevent or treat infection. Transfusion is not generally
used for patients with a low neutrophil count, but can be used in patients with high fever,
infection that is unresponsive to antibiotics, blood fungal infections or septic shock.
Growth factors may be given to the patient to stimulate the marrow to make new white
cells.
Graft versus host disease. If you undergo an allogeneic stem cell transplantation, you're at
high risk of developing graft versus host disease (GVHD). The older you are, the higher
your risk for GVHD. GVHD develops when the donor's immune cells mistakenly attack
the patient's normal cells. GVHD can be mild, moderate or severe - even life threatening.
Kidney stones. Some AML patients may build up uric acid in their blood as a result of a
very high white cell count. The use of chemotherapy may also increase uric acid, which
is a chemical in the cell. Uric acid enters the blood and is excreted in the urine. If many
cells are killed simultaneously by therapy, the amount of uric acid in the urine can be so
high that kidney stones can form. This may seriously interfere with the flow of urine.
Drugs such as allopurinol (Zyloprim) or rasburicase (Elitek) can be given to minimize
the buildup of uric acid in the blood.

The following side effects are also common. Click here to read more about these side effects.

Mouth ulcers
Diarrhea
Temporary hair loss
Rashes
Nausea and vomiting
Fatigue

Long-Term and Late Effects of Treatment

Treatment for individuals who have AML sometimes causes effects that continue after treatment
ends (long-term effects) or develop much later in life (late effects). Various factors can influence
the risk of developing long-term or late effects, including

Type and duration of treatment

Age at the time of treatment
Gender and overall health.

Most AML patients are treated with an anthracycline, like daunorubicin. Anthracyclines have
been associated with increased risk for heart muscle injury or chronic heart failure. Heart disease
may not become apparent until many years after therapy ends. Stem cell transplantation is used
to treat some patients with AML. It has been associated with long-term or late effects, including
infertility, thyroid dysfunction, chronic fatigue and risk for developing a second cancer
(lymphoma; melanoma of the skin; or cancer of the tongue and salivary glands, central nervous
system, bone, soft tissue and thyroid gland). The number of patients who develop secondary
cancers is small. These and other possible long-term and late effects can be managed.

For more information see the free The Leukemia & Lymphoma Societys free publications:

Long-Term and Late Effects of Treatment in Adults

Long-Term and Late Effects of Treatment for Childhood Leukemia and Lymphoma
Facts.

Acute myeloid leukemia (AML) can be a difficult disease to cure. However, advances in AML
treatment have resulted in improved remission (an absence of signs and symptoms) and cure
rates.

Treatment outcomes can be broken down into four categories. The table below describes the
difference between each category.

Terms for AML Treatment Outcomes

AML is still present during treatment or after treatment (refractory)
or AML has come back after treatment (relapsed).
Active disease A patient with relapsed AML has more than 5 percent blast cells in
the marrow.

No AML cells are detected in bone marrow using standard tests.

But more sensitive tests, such as flow cytometry, or very sensitive
Minimal residual
tests, such as polymerase chain reaction (PCR), detect remaining
disease
AML cells in the marrow.

No evidence of disease after treatment, (complete based on

remission):
o Less than 5 percent blast cells in the marrow
Remission
o Blood cell counts within normal limits
o No signs or symptoms of the disease

No evidence of AML cells in the marrow when using very

Complete molecular
sensitive tests such as PCR.
remission

Refractory Leukemia
Most patients achieve a remission (an absence of signs and symptoms) after initial treatment for
acute myeloid leukemia (AML). However, some patients have residual leukemic cells in their
marrow even after intensive treatment. This is referred to as "refractory leukemia."

For refractory AML, treatment options may include drugs not already used during the first
course of treatment. Stem cell transplantation may be used when remission is achieved, which
may result in a more durable remission

Relapsed Leukemia
Some patients reach remission and then have a return of leukemia cells in the marrow and a
decrease in normal blood cells. This is called relapsed leukemia.

In patients who relapse, the duration of the remission, the patients age and the cytogenetic
findings in the leukemia cells influence the approach to therapy. Drugs similar to those
administered initially, different drugs or stem cell transplantation may be used to treat the
leukemia.

Stem Cell Transplantation in Relapsed Patients

Allogeneic stem cell transplantation may be a treatment option for patients in early first relapse
or second remission, although this is a high-risk procedure. For patients who lack a sibling
donor, matched-unrelated donor transplants can be effective. Patients with AML who relapse
after allogeneic stem cell transplantation may have a long-term remission if they have a second
transplant. Donor leukocyte infusion is sometimes used to treat relapsed AML post transplant.
This therapy is most effective in early relapses and in the absence of extensive chronic graft-
versus-host disease (GVHD).

Clinical Trials
For some patients with relapsed or refractory AML, the best treatment route may be one that is
being studied in a clinical trial. Several drugs and drug combinations used to treat AML are
currently being studied.

https://www.lls.org/leukemia/acute-myeloid-leukemia