Acute Myeloid Leukemia

What is Acute Myeloid Leukemia (AML)?

• An estimated 12,330 people diagnosed in the world
in 2010
• Second most common type of leukemia in adults
• Affects the production of neutrophils
• Found in the blood and bone marrow; can invade
other areas such as the brain and skin to make a
chloromas
• Develops quickly and often needs immediate
treatment

What is the Function of Neutrophils?

• Part of the immune system
• Help fight infections caused
by bacteria
• Develop from immature
white blood cells
(differentiation)
• Produced rapidly during an
infection and return to
regular level when
infection is controlled

Function of Neutrophils cont…

• In AML, too many
immature cells called
myeloblasts or blasts
build up in the blood
and bone marrow
• Blasts do not function
like fully developed,
healthy blood cells

 What are the Risk Factors for AML?

• Age: AML is more common in older adults, but it occurs at all ages.
About half of people with AML are older than 65 years when diagnosed.
• Smoking
• Certain genetic disorders: such as Down syndrome and Klinefelter
syndrome
• High doses of radiation e.g. survivors of atomic bombs
• Previous cancer treatment
• The chemical benzene found in petroleum, cigarette smoke, and
industrial workplaces, raises the risk of AML.
• Prior history of bone marrow disease (e.g. myelodysplastic syndrome,
or aplastic anemia) can cause secondary AML with risk of poor
prognosis.

 What are the Symptoms of AML?

-Fatigue -Weakness
-Fever -Weight loss
-Easy bruising or bleeding
-Bone or abdominal pain
-Difficulty breathing or shortness of breath
-Frequent infections
-Swollen lymph nodes
-Swollen or bleeding gums

 How is AML Diagnosed?

• Blood tests to count the number of white blood
cells and examine their appearance under a
microscope (morphology)
• Diagnosis is confirmed with a bone marrow biopsy
• Flow cytometry (immunophenotyping, protein
expressed by cells) and cytochemistry to distinguish
AML from other types of leukemia
• Cytogenetics to identify genetic changes in AML
cells

 Immunophenotyping
• Immunophenotyping is a technique used to study the
protein expressed by cells. This can be done on tissue
section (fresh or fixed tissue), cell suspension, etc.
• An example is the detection of tumor marker, such as in
the diagnosis of leukemia. It involves the labelling of
white blood cells with antibodies directed against
surface proteins on their membrane.
• By choosing appropriate antibodies, the differentiation of
leukemic cells can be accurately determined.
• The labelled cells are processed in a flow cytometer, a
laser-based instrument capable of analyzing thousands of
cells per second.
• The whole procedure can be performed on cells from the
blood, bone marrow or spinal fluid in a matter of a few
hours.

 Cytochemistry
• Cytochemistry is the biochemistry of cells,
especially that of the macromolecules
responsible for cell structure and function.
• The term is also used to describe a process of
identification of the biochemical content of
cells.

 Cytogenetics
• Cytogenetics is a branch of genetics that is
concerned with the study of the structure and
function of the cell, especially the
chromosomes.
 What are the Types of AML?
• There are several different subtypes of AML
• All subtypes cause a decrease in normal blood
counts
• Some subtypes have specific symptoms and
problems
• There can be widely different results after
treatment based on the subtype
• Subtype is named according to the type of normal,
immature white blood cell it most closely
resembles

 How is AML Classified?

• Subtype is described by morphology
• The World Health Organization (WHO) and French-
American-British (FAB) classification systems are
frequently used to describe AML (M0-M7)
• Also classified by the cytogenetic
(chromosome) changes and molecular
genetics in the leukemia cells

 Cytogenetic Classification
• Cytogenetic changes and molecular genetics can
determine prognosis (chance of recovery),
influence the choice of treatment and help predict
the results of treatment
• Favorable: presence of changes associated with a
good outcome after treatment (translocation
t(8:21), and t(15:17).
• Intermediate: presence of changes associated with
a less favorable prognosis (t(19:11).
• Unfavorable: presence of changes associated with a
poor prognosis (5q deletion).

 How is AML treated ?

• In general, the favourable changes occur more commonly in
younger patients, while the unfavorable changes are more
common in patients older than 60 years.
• How well treatment works still varies widely in each of these
groups.
• Treatment is successful in the long term for 50% to 60% of
patients with AML that is classified as favorable and for less
than 10% of patients with AML that is classified as unfavorable.
• How well treatment works also depends on the following
factors: the patient's age, patient’s general health, the number
of white blood cells, previous hematologic disorder,
unfavourable karyotype.

 How is AML Treated?

• It is not possible to predict exactly the likelihood of
successful treatment for a person with AML.
• Treatment depends on subtype, morphology,
cytogenetics, molecular genetics, and the patient’s
overall health
– Chemotherapy (options include a combination of drugs)
– Radiation therapy
– Bone marrow transplantation/stem cell transplantation
• More than one treatment may be used

 AML Treatment: Chemotherapy

• Primary treatment for • Divided into two main
AML phases: remission
• Systemic chemotherapy induction and post-
is given directly into the remission consolidation
bloodstream or by • Side effects may include
mouth, targeting cancer hair loss, mouth sores,
cells throughout the body fatigue, infection,
• Chemotherapy may also bleeding, nausea,
be injected into the vomiting and infertility
cerebrospinal fluid

 Remission Induction Chemotherapy

• Initial period of treatment • Combination therapy of
after diagnosis cytarabine (Cytosar-U,
• Intensive therapy kills both Tarabine PFS, 7 days) and
leukemia cells and healthy daunorubicin (Cerubidine,
cells Rubidomycin, 3 days) or
idarubicin (Idamycin, 3 days)
• Goal is complete remission is common
(normal blood counts, no
evidence of leukemia in • May require hospitalization
for three to five weeks
bone marrow and no AML
symptoms) • May require two courses of
induction chemotherapy for
complete remission

 Consolidation or Intensification
Chemotherapy
• Used to kill remaining AML cells after successful
induction
• Two to four courses of high-dose cytarabine is used for
younger adults in remission
• Many different regimens are used for older patients.
• In 2020, the FDA approved oral azacitidine for
consolidation after complete remission.
• Stem cell transplantation may be recommended
instead

 AML Treatment: Stem Cell Transplantation/Bone

Marrow Transplantation
• New stem cells are introduced from the patient (autologous)
or a donor (allogeneic) to form new blood cells
• May be used for patients at high risk for recurrence
• A patient’s bone marrow is treated with high doses of
chemotherapy and/or radiation therapy to decrease the
leukemia cells and prevent immune cells from attacking the
donated stem cells

• Graft-versus-host disease: a serious complication in which

the donor’s immune cells attack the patient’s healthy cells

AML Treatment: Radiation Therapy

• External beam: outside the body
• Used most often for AML that has spread to
the brain or to shrink localized masses called
chloromas (myeloid sarcoma)
• Side effects may include fatigue, mild skin
reactions, nausea and vomiting, and diarrhea

 After Treatment
• Blood tests to monitor recovery from
treatment
• Bone marrow biopsies to determine post-
treatment remission status
• Long-term follow-ups to monitor for late
effects of treatment