Circulating Kinetics and Morphology

of Neutrophils 2 of 3

► Two types of granules:

 Primary or azurophilic
 Secondary or specific
► Allgranules contain enzymes which are
involved in killing and digesting bacteria and
fungi.
► Neutrophils are very mobile cells.

1
 Circulating Kinetics and Morphology
of Neutrophils 3 of 3

► Once in the circulatory system, the neutrophils

divide up into two pools:
 Marginating pool: These neutrophils remain in the
circulatory system searching for an area of
inflammation. When inflammation is found, these
neutrophils leave the circulatory system by process of
diapedesis and enter surrounding tissues.
 Circulating pool: Leave the blood stream by random
migration and do not return to the bloodstream.
► Neutrophils are believed to survive 2-5 days after
entering the tissues.
2
Neutrophil Counts in Peripheral Blood

► Variations in the numbers of neutrophils is a

useful diagnostic tool; Variations reflect
response of neutrophils to underlying
disease (i.e. bacterial infection) or of
another disorder such as leukemia.
► Normal ranges vary widely with age:
 Newborns may have more WBCs
 Babies may have more lymphocytes
3
Neutrophil
Function

4
 Neutrophil Function

► Main function is destruction of

microorganisms through process called
phagocytosis.
► Once bacteria infiltrate tissues, neutrophils
immediately respond. Phagocytosis begins.
► Phagocytosis consists of three phases:
 migration and diapedesis
 opsonization and recognition
 ingestion, killing, and digestion
5
 Migration and Diapedesis
Phase 1

► Neutrophils are attracted to the area by

chemical signals produced by inflammation,
injury, and infectious agents.
► Chemotaxis is the movement of
neutrophils towards the chemoattractant.
► Neutrophils migrate from the vessels by
diapedesis between the endothelial cells of
the vessels, and migrate towards the
chemoattractor.
6
 Opsonization and Recognition
Phase 2
► Neutrophils cannot recognize or attach to
microorganisms. They need help.
► Opsonization is process which facilitates
recognition and attachment of neutrophil to
organism. Marks organism for ingestion by
neutrophil.
► As chemotaxis occurring, immunoglobulins and
complement components coat surface of bacteria.
Marked bacteria (opsonin) easily recognized by
neutrophil and ingested.
► Ingestion requires presence of membrane-bound
immunoglobulin.
7
 Ingestion, Killing and Digestion
Phase 3 1 of 2

► Ingestion begins as soon as organism and

neutrophil bind together. Membrane pseudopods
surround organism, forming isolated vacuole
within cytoplasm of neutrophil. Called a
phagosome.
► Simultaneously, cytoplasmic granules migrate to
and fuse with phagosome, forming a
phagolysosome.
► Once phagolysosome formation complete,
granules release contents. Ingested organism
exposed to lytic activity of granular enzymes that
leads to death of organism and its eventual
digestion.
8
 Ingestion, Killing and Digestion
Phase 3 2 of 2

► Inthe leukocyte, there are pH changes,

dumping of digestive enzymes into the
phagolysosome, production of hydrogen
peroxide and superoxides. These digestion
processes are collectively called
respiratory burst. These oxygen
metabolites injure the organism and interact
with other granular contents to produce
toxic agents such as hydrochloric acid
(household bleach).
9
 WBC DISORDERS

Disorders of white blood cells can be

classified into two broad categories:
proliferative disorders, in which there is an
expansion of leukocytes, and leukopenias,
which are defined as a deficiency of
leukocytes.
 PROLIFERATIVE

• Proliferations of white cells can be reactive or

neoplastic.
• Since the major function of leukocytes is host
defense, reactive proliferation in response to
an underlying primary, often microbial,
disease is fairly common. Neoplastic
disorders, although less frequent, are much
more important clinically.
 Leukopenia
• The number of circulating white cells may
be markedly decreased in a variety of
disorders.
• An abnormally low white cell count
(leukopenia) usually results from reduced
numbers of neutrophils (neutropenia,
granulocytopenia).
 Leukopenia
• Lymphopenia is less common; in addition to
congenital immunodeficiency diseases, it is most
commonly observed in specific settings, such as
advanced HIV infection, following therapy with
glucocorticoids or cytotoxic drugs, autoimmune
disorders, malnutrition, and certain acute viral
infections.
• Only the more common leukopenias involving
granulocytes will be discussed further here.
 Pathogenesis.
• A reduction in circulating granulocytes will
occur if there is (1) reduced or ineffective
production of neutrophils or (2) accelerated
removal of neutrophils from the circulating
blood.
 Pathogenesis.
• (1) Inadequate or ineffective granulopoiesis is
observed in the setting of:
• 1. Suppression of myeloid stem cells, as occurs
in aplastic anemia and a variety of infiltrative
marrow disorders (tumors, granulomatous
disease, etc.);
• in these conditions, granulocytopenia is
accompanied by anemia and thrombocytopenia.
 Pathogenesis.
• 2. Suppression of committed granulocytic precursors
due to exposure to certain drugs.
• Drugs are responsible for most of the significant
neutropenias . Certain drugs, such as alkylating agents
and antimetabolites used in cancer treatment, produce
agranulocytosis in a predictable, dose-related fashion.
• Because such drugs cause a generalized suppression of
the bone marrow, production of erythrocytes and
platelets is also affected
 Pathogenesis.
• 3. Disease states associated with ineffective
granulopoiesis, such as megaloblastic anemias
due to vitamin B12 or folate deficiency and
myelodysplastic syndromes, where defective
precursors are susceptible to death in the marrow.
• 4. Rare inherited conditions (such as Kostmann
syndrome) in which genetic defects in specific
genes result in impaired granulocytic
differentiation.
 Pathogenesis.
• (2) Accelerated removal or destruction of
neutrophils occurs with
• 1. Immunologically mediated injury to the
neutrophils, which may be idiopathic,
associated with a well-defined immunologic
disorder (e.g., systemic lupus
erythematosus), or produced by exposure to
drugs.
 Pathogenesis.
• 2. Splenic sequestration, in which excessive
destruction occurs secondary to enlargement
of the spleen, usually associated with
increased destruction of red cells and
platelets as well.
• 3. Increased peripheral utilization, as may
occur in overwhelming bacterial, fungal, or
rickettsial infections.
 Morphology
• Bone marrow:
• The anatomic alterations in the bone marrow
vary according to the underlying cause.
• When neutropenia is caused by excessive
destruction of mature neutrophils, the marrow
is usually hypercellular owing to the
presence of increased numbers of
granulocytic precursors.
 Morphology
Bone marrow:
•Hypercellularity is also the rule in neutropenias
associated with ineffective granulopoiesis, as
occurs in megaloblastic anemias and
myelodysplastic syndromes.
•Agranulocytosis caused by agents that suppress or
destroy granulocytic precursors is understandably
associated with marrow hypocellularity.
 Morphology
Other organ:
•Infections (most often bacterial or fungal) are a common
consequence of agranulocytosis.
•Ulcerating necrotizing lesions of the gingiva, floor of the mouth, buccal
mucosa, pharynx, or anywhere within the oral cavity are quite
characteristic.
•These ulcers are typically deep, undermined, and covered by gray to
green-black necrotic membranes from which numerous bacteria or fungi
can be isolated.
•Less frequently, similar ulcerative lesions occur in the skin, vagina,
anus, or gastrointestinal tract.
 Morphology
Other organ:
•Severe life-threatening invasive bacterial or fungal infections can
occur in the lungs, urinary tract, and kidneys. The neutropenic patient
is at particularly high risk for deep fungal infections caused by
organisms such as Candida and Aspergillus.
•Sites of infection often show a massive growth of organisms with
little leukocytic response. In the most dramatic instances, bacteria
grow in colonies resembling those seen on nutrient media.
•The regional lymph nodes draining these infections are enlarged and
inflamed.
 Clinical Course
• The symptoms and signs of neutropenias are
related to bacterial or fungal infections. They
include malaise, chills, and fever, followed in
sequence by marked weakness and fatigability.
• In severe agranulocytosis with virtual absence
of neutrophils, these infections can be
overwhelming and cause death within a few
days.
 Clinical Course
• A neutrophil count of less than 1000
cells per mm3 of blood is worrisome, but
most serious infections occur with counts
below 500 per mm3.
• Because infections are often fulminant,
broad-spectrum antibiotics are given
expeditiously whenever signs or
symptoms appear.
 Clinical Course
• In some instances, such as following
myelosuppressive chemotherapy,
neutropenia is treated with granulocyte
colony-stimulating factor (G-CSF), a
growth factor that stimulates the
production of granulocytes from marrow
precursors
 Reactive Proliferations of
White Cells
• Definition: Leukocytosis refers to an
increase in the number of blood leukocytes.
• It is a common reaction to a variety of
inflammatory states and is sometimes the
first indication of neoplastic growth of
leukocytes
 Pathogenesis
• The peripheral blood leukocyte count is
influenced by several factors, including:
• 1. The size of the myeloid (for granulocytes
and monocytes) and lymphoid (for
lymphocytes) precursor and storage cell
pools in the bone marrow, circulation, and
peripheral tissues.
 Pathogenesis
• 2. The rate of release of cells from the
storage pool into the circulation
• 3. The proportion of cells that are adherent
to blood vessel walls at any time
• 4. The rate of extravasation of cells from
the blood into tissues
 Pathogenesis
• leukocyte homeostasis is maintained by
cytokines, growth factors, and adhesion
molecules through their effects on the
commitment, proliferation, differentiation,
and extravasation of leukocytes and their
progenitors.
 Pathogenesis
• In acute infection, there is a rapid increase in the egress of
mature granulocytes from the bone marrow pool.
• The release of IL-1, TNF, and other inflammatory
cytokines stimulates bone marrow stromal cells and T
cells to produce increased amounts of colony-stimulating
factors (CSFs), which enhance the proliferation and
differentiation of committed granulocytic progenitors and,
over several days, cause a sustained increase in neutrophil
production
 Pathogenesis
• Other growth factors preferentially stimulate other
types of leukocytosis.
• For example, IL-5 causes eosinophilia by
enhancing the growth, survival, and differentiation
of eosinophils, while IL-7 plays a central role in
lymphopoiesis.
• Such factors are differentially produced in
response to various pathogenic stimuli
 Causes of Leukocytosis
Neutrophilic Acute bacterial infections, especially
leukocytosis those caused by pyogenic
organisms; sterile
inflammation(myocardial infarction,
burns)
Eosinophilic Allergic disorders such as asthma,
leukocytosis allergic skin diseases; parasitic
(eosinophilia) infestations; drug reactions; certain
malignancies (e.g., Hodgkin disease
and some non-Hodgkin lymphomas);
collagen vascular disorders and some
vasculitides; atheroembolic disease
Basophilic Rare, often indicative of a
leukocytosis myeloproliferative disease (e.g.,
(basophilia) chronic myelogenous leukemia)
Monocytosis Chronic infections (e.g., tuberculosis),
bacterial endocarditis and malaria;
collagen vascular diseases (e.g.,
systemic lupus erythematosus) and
inflammatory bowel diseases (e.g.,
ulcerative colitis)
Lymphocytosis Accompanies monocytosis in many
disorders associated with chronic
immunologic stimulation (e.g.,
tuberculosis); viral infections (e.g.,
hepatitis)
 Pathogenesis
• In most instances, it is not difficult to distinguish
reactive leukocytosis from leukocytosis caused by
flooding of the peripheral blood by neoplastic white
blood cells (leukemia).
• Uncertainties may arise in two settings:
• 1. Particularly in children, acute viral infections can
produce the appearance of activated lymphocytes in
the peripheral blood and marrow that resemble
neoplastic lymphoid cells.
 Pathogenesis

• 2. At other times, particularly in inflammatory

states and severe chronic infections, many
immature granulocytes appear in the blood,
simulating a picture of myelogenous leukemia
(leukemoid reaction).
• Special laboratory studies (discussed later) are
helpful in distinguishing reactive and
neoplastic leukocytoses.
 Reactive Proliferations of
Lymph Nodes
• In addition to causing leukocytosis,
infections and inflammatory stimuli often
elicit immune reactions within lymph nodes.
• The infections that lead to lymphadenitis are
numerous.
• Most cause stereotypic patterns of lymph
node reaction designated acute and chronic
nonspecific lymphadenitis
Acute nonspecific lymphadenitis
• Lymph nodes undergo reactive changes
whenever they are challenged by
microbiologic agents, cell debris, or foreign
matter introduced into wounds or into the
circulation. Acute lymphadenitis is most often
seen:
• 1. in the cervical region due to microbial
drainage from infections of the teeth or tonsils
Acute nonspecific lymphadenitis
• 2. in the axillary or inguinal regions
secondary to infections in the extremities
• 3. mesenteric lymph nodes draining acute
appendicitis.
• 4. Systemic viral infections (particularly in
children) and bacteremia often produce
generalized lymphadenopathy.
 Morphology
• Macroscopically, the nodes become swollen,
gray-red, and engorged.
• Histologically, there is prominence of the
lymphoid follicles, with large germinal centers
containing numerous mitotic figures.
• Macrophages often contain particulate debris
of bacterial origin or derived from necrotic
cells.
 Morphology
• When pyogenic organisms are the cause of the reaction,
the centers of the follicles may undergo necrosis, the
entire node can sometimes be converted into a
suppurative mass.
• With less severe reactions, there is a neutrophilic
infiltrate about the follicles, and numerous neutrophils
can be found within the lymphoid sinuses. The cells
lining the sinuses become hypertrophied and cuboidal
and often undergo hyperplasia.
 Clinical appearence
• nodes with acute lymphadenitis are enlarged because of the
cellular infiltration and edema.
• As a consequence of the distention of the capsule, they are
tender to touch. When abscess formation is extensive, they
become fluctuant.
• The overlying skin is frequently red, and sometimes
penetration of the infection to the skin surface produces
draining sinuses, particularly when the nodes have undergone
suppurative necrosis. As might be expected, healing of such
lesions is associated with scarring.
Chronic nonspecific lymphadenitis
• lymph nodes in chronic reactions are not
tender, because their capsules are not under
increased tension.
• Chronic lymphadenitis is particularly
common in inguinal and axillary nodes,
which drain relatively large areas of the
body and are frequently challenged.
 Neoplastic Proliferations of
White Cells
• Malignant proliferative diseases constitute
the most important disorders of white cells.
• These diseases can be classified into several
categories:
• 1. Lymphoid neoplasms
• 2. Myeloid neoplasms
• 3. histiocytoses
 Categories
• Myeloid neoplasms arise from hematopoietic stem cells that give
rise to cells of the myeloid (i.e., erythroid, granulocytic, and/or
thrombocytic) lineage. Three categories of myeloid neoplasia are
recognized: 1. acute myelogenous leukemias, in which immature
progenitor cells accumulate in the bone marrow; 2.
myelodysplastic syndromes, which are associated with ineffective
hematopoiesis and resultant peripheral blood cytopenias; and 3.
chronic myeloproliferative disorders, in which increased
production of one or more terminally differentiated myeloid
elements usually leads to elevated peripheral blood counts.
 Categories
• Lymphoid neoplasms encompass a diverse
group of entities. In many but not all
instances, the phenotype of the neoplastic
cell closely resembles that of a particular
stage of normal lymphocyte differentiation,
a feature that is used in the diagnosis and
classification of these disorders.
 Categories
• The histiocytoses are uncommon proliferative lesions of
macrophages and dendritic cells.
• "histiocyte" is often applied to cells of macrophage or
dendritic-cell lineage.
• A special category of immature dendritic cells referred to
as Langerhans cells gives rise to a spectrum of neoplastic
disorders, some of which behave as disseminated malignant
tumors, and others as localized benign proliferations. This
group is called Langerhans cell histiocytoses.
 Etiology and pathogenesis
1. Chromosomal translocations and
oncogenes. Nonrandom chromosomal
abnormalities, most commonly
translocations, are present in the majority
of white cell neoplasms. Many specific
rearrangements are associated with
particular neoplasms, suggesting a critical
role in their genesis.
 Etiology and pathogenesis
• Chromosomal translocations frequently
occur in myeloid neoplasms
 Etiology and pathogenesis
• 2. Inherited genetic factors ： individuals
with genetic diseases that promote genomic
instability.
• telangiectasia, are at increased risk for
development of acute leukemia. In addition,
both Down syndrome (trisomy 21) and
neurofibromatosis type I are associated with
an increased incidence of childhood leukemia.
 Etiology and pathogenesis
3. Viruses.
Three viruses-human T-cell leukemia
virus-1 (HTLV-1), Epstein-Barr virus (EBV),
and Kaposi sarcoma herpesvirus/human
herpesvirus-8 (KSHV/HHV-8) have been
implicated as causative agents.
 Etiology and pathogenesis
• HTLV-1 has been associated only with adult T-cell
leukemia/lymphoma.
• EBV genomes are found in the tumor cells of a subset of
Burkitt lymphoma, 30% to 40% of cases of Hodgkin
lymphoma, many B-cell lymphomas occurring in the
setting of T-cell immunodeficiency, and rare natural killer
cell lymphomas.
• KSHV is uniquely associated with an unusual type of B-
cell lymphoma that presents as a malignant effusion, often
in the pleural cavity.
 Etiology and pathogenesis
• 4. Environmental agents.

• The most clear-cut associations are those of

Helicobacter pylori infection with gastric B-
cell lymphoma and gluten-sensitive
enteropathy with intestinal T-cell lymphoma.
 Etiology and pathogenesis
• 5. Iatrogenic factors.
• Radiotherapy and certain forms of chemotherapy
used to treat cancer increase the risk of
subsequent myeloid and lymphoid neoplasms.
• This association is believed to stem from
mutagenic effects of ionizing radiation and
chemotherapeutic drugs on hematolymphoid
progenitor cells.
 Myeloid neoplasm
• The common feature that unites this
heterogeneous group of neoplasms is an
origin from hematopoietic progenitor cells
capable of giving rise to terminally
differentiated cells of the myeloid series
(erythrocytes, granulocytes, monocytes, and
platelets).
 categories
• Acute myelogenous leukemias, characterized by the
accumulation of immature myeloid forms in the bone
marrow and the suppression of normal hematopoiesis
• Myelodysplastic syndromes, associated with
ineffective hematopoiesis and associated cytopenias
• Chronic myeloproliferative disorders, usually
associated with an increased production of terminally
differentiated myeloid cells
 Acute myelogenous leukemias
• Acute myelogenous leukemias affect
primarily adults, peaking in incidence
between the ages of 15 and 39 years, but are
also observed in older adults and children.
• AML is quite heterogeneous, reflecting the
complexities of myeloid cell differentiation
 Pathophysiology
• Most AMLs are associated with acquired genetic
alterations that inhibit terminal myeloid differentiation. As
a result, normal marrow elements are replaced by
relatively undifferentiated blasts exhibiting one or more
types of early myeloid differentiation.
• The replication rate of these blasts is actually lower than
that of normal myeloid progenitors, highlighting the
pathogenic importance of blocked maturation and
increased survival.
 Pathophysiology
• In all AMLs, the accumulation of proliferating
neoplastic myeloid precursor cells in the marrow
suppresses remaining normal hematopoietic
progenitor cells by physical replacement as well as by
other unknown mechanisms.
• The failure of normal hematopoiesis results in anemia,
neutropenia, and thrombocytopenia, which cause most
of the major clinical complications of AML.
 Pathophysiology
• Therapeutically, the aim is to clear the bone
marrow of the leukemic clone, thus permitting
resumption of normal hematopoiesis. This can be
accomplished by treatment with cytotoxic drugs
or, in the specific case of acute promyelocytic
leukemia, by overcoming the block in
differentiation with pharmacologic doses of
retinoic acid.
 Chromosomal Abnormalities
• Particular chromosomal abnormalities
correlate with the clinical setting in which
the tumor occurs. AML arising de novo in
patients with no risk factors are often
associated with balanced chromosomal
translocations, particularly t(8;21), inv(16),
and t(15;17).
 Chromosomal Abnormalities
• In contrast, AMLs following
myelodysplastic syndromes or exposure
to DNA-damaging agents (such as
chemotherapy or radiation therapy) are
commonly associated with deletions or
monosomies involving chromosomes 5
and 7 and usually lack chromosomal
translocations.
 Classification
• In the most widely used system in current use, AML is
divided into eight (M0 to M7) categories.
• This scheme takes into account both the degree of
maturation (M0 to M3) and the lineage of the leukemic
blasts (M4 to M7).
• Histochemical stains for peroxidase, specific esterase,
and nonspecific esterase, and immunostains for myeloid
specific antigens play important roles in defining the
type of myeloid differentiation that blasts exhibit.
 French-American-British (FAB) Classification of AML
FAB Approximate % of
subtype Name adult patients Prognosis
M0 Undifferentiated acute 5% Worse
myeloblastic leukemia
M1 Acute myeloblastic 15% Average
leukemia with minimal
maturation
M2 Acute myeloblastic 25% Better
leukemia with maturation
M3 Acute promyelocytic 10% Best
leukemia
M4 Acute myelomonocytic 20% Average
leukemia
M4 eos Acute myelomonocytic 5% Better
leukemia with eosinophilia
M5 Monocytic leukemia 10% Average
M6 Acute erythroid leukemia 5% Worse
M7 Acute megakaryoblastic 5% Worse
leukemia
 Morphology

• The diagnosis of AML is based on finding

that myeloid blasts make up more than
20% of the cells in the marrow
Diffuse replacement of normal haematopoiesis in bone
marrow by leukemic cells
 Morphology
• Myeloblasts have :
• delicate nuclear chromatin.
• two to four nucleoli.
• and more voluminous cytoplasm than
Lymphoblasts.
• The cytoplasm often contains fine,
azurophilic ,peroxidase-positive granules.
 Morphology
• Distinctive red-staining peroxidase-positive
structures called Auer rods, which represent
abnormal azurophilic granules, are present in
many cases and are particularly numerous in
acute promyelocytic leukemia.
• The presence of Auer rods is taken to be
definitive evidence of myeloid differentiation.
 Morphology
• Monoblasts often have folded or lobulated
nuclei, lack Auer rods, and are peroxidase
negative and nonspecific esterase positive.
• In some AMLs, blasts exhibit megakaryocytic
differentiation, which is often accompanied
by marrow fibrosis caused by the release of
fibrogenic cytokines.
• Rarely, the blasts of AML show evidence of
erythroid differentiation (erythroblasts)..
 Morphology
• The number of leukemic cells in the peripheral
blood is highly variable. Blast counts can be
more than 100,000 cells per microliter but are
under 10,000 cells per microliter in about 50%
of the patients.
• Occasionally, the peripheral smear might not
contain any blasts (aleukemic leukemia). For
this reason, bone marrow examination is
essential to exclude acute leukemia in
pancytopenic patients.
 Acute
myelogenous
leukemia
(FAB M1
subtype).

• Myeloblasts have delicate nuclear chromatin, prominent

nucleoli, and fine azurophilic granules in the cytoplasm
 Acute
promyelocytic
leukemia
(FAB M3
subtype).

• Bone marrow aspirate shows neoplastic promyelocytes with abnormally coarse and numerous
azurophilic granules. Other characteristic findings include the presence of several cells with
bilobed nuclei and a cell in the center of the field that contains multiple needlelike Auer rods
 Acute
monocytic
leukemia
(FAB M5b
subtype).

• Peripheral smear shows one monoblast and five

promonocytes with folded nuclear membranes
 Clinical Features
• Most patients present within weeks or a few
months of the onset of symptoms related to
anemia, neutropenia, and
thromobocytopenia, most notably fatigue,
fever, and spontaneous mucosal and
cutaneous bleeding.
•
 Clinical Features
• Often, the bleeding diathesis caused by
thrombocytopenia is the most striking clinical feature.
Cutaneous petechiae and ecchymoses, serosal
hemorrhages into the linings of the body cavities and
viscera, and mucosal hemorrhages into the gingivae
and urinary tract are common. Procoagulants and
fibrinolytic factors released by leukemic cells,
especially in acute promyelocytic leukemia (M3),
exacerbate the bleeding diathesis.
Cutaneous petechiae and ecchymoses
 Clinical Features
• Infections are frequent, particularly in the oral
cavity, skin, lungs, kidneys, urinary bladder, and
colon, and are often caused by opportunists such
as fungi, Pseudomonas, and commensals.
 Clinical Features
• Signs and symptoms related to infiltration of
tissues are usually less striking in AML.
• Mild lymphadenopathy and organomegaly can
occur. In tumors with monocytic differentiation
(M4 and M5), infiltration of the skin (leukemia
cutis) and the gingiva can be observed, likely
reflecting the normal tendency of non-neoplastic
monocytes to extravasate into tissues
 Clinical Features
• Central nervous system spread is less common than in
ALL but still seen.
• Quite uncommonly, patients present with localized
masses composed of myeloblasts in the absence of
marrow or peripheral blood involvement. These
tumors, known variously as myeloblastomas,
granulocytic sarcomas, or chloromas, inevitably
progress to systemic AML over a period of up to
several years.
 Prognosis
• AML is a difficult disease to treat.
• Approximately 60% of the patients achieve
complete remission with chemotherapy, but
only 15% to 30% remain free from disease
for 5 years.
• AMLs associated with t(8;21) or inv(16)
have a relatively good prognosis with
conventional chemotherapy.
 Prognosis
• In contrast, the prognosis is dismal for
patients with AML with prior myelodysplastic
syndrome or following genotoxic therapy,
possibly because of damage to normal
hematopoietic stem cells. These "high-risk"
forms of AML, as well as relapsed AML of all
types, are increasingly being treated with
allogeneic bone marrow transplantation.