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LEUKEMIAS
H.A. MWAKYOMA, MD
LEUKEMIAS
 Background.
• Leukemias are a group of heterogeneous neoplastic
disorders of white blood cells. Based on their origin,
 myeloid or
 lymphoid,
• They can be divided into 2 types.
 Leukemias traditionally have been designated as
 acute
- Acute leukemias usually present with hemorrhage,
anemia, infection, or infiltration of organs OR
 chronic, based on their untreated course.
LEUKEMIAS- Background---cont
• Many patients with chronic leukemias are
asymptomatic.
• Other leukemias present with
splenomegaly, fever, weight loss, malaise,
frequent infections, bleeding, thrombosis, or
lymphadenopathy.
• Some chronic leukemias enter a blast
phase where the clinical manifestations are
similar to the acute leukemias.
Classification
• Clinically and pathologically, leukemia is
subdivided into a variety of large groups. The first
division is between its acute and chronic forms:
 ACUTE:
• Acute lymphoblastic leukemia (ALL)
• Acute myelogenous leukemia (AML)
(or myeloblastic)
 CHRONIC:
• Chronic lymphocytic leukemia (CLL)
• Chronic myelogenous leukemia (CML)
Pathophysiology
• In leukemias, a clone of malignant cells may arise
at any stage of maturation, that is, in the
lymphoid, myeloid, or pluripotential stage.
• The cause for this clonal expansion is poorly
understood in most cases, but it appears to
involve some rearrangement of the DNA.
• External factors, such as
 alkylating drugs,
 ionizing radiation, and
 chemicals, and
• internal factors, such as chromosomal
abnormalities, lead to DNA changes
Pathophysiology—cont-- Chromosomal rearrangements may alter the
structure or regulation of cellular oncogenes.
• For instance,
in the B-cell lymphocytic leukemias,
chromosomal translocations may put the
genes that normally regulate heavy and
light chain immunoglobulin synthesis next
to the genes that regulate normal cellular
activation and proliferation.
 This results in proliferation of lymphoblasts.
Pathophysiology—cont--• As the population of cells expands, the bone
marrow starts to fail.
• Pancytopenia is typical and results in part
from the physical replacement of normal
marrow elements by the immature cells.
• In addition, the abnormal cells may secrete
factors that inhibit normal hematopoiesis.
Pathophysiology—cont--• As the bone marrow becomes replaced, the
abnormal cells spill into the circulation and
infiltrate other organs, such as
 the liver,
 the spleen, and
 the eye.
 The ocular manifestations may be secondary to
direct infiltration of the leukemic cells, as a result
of abnormal systemic hematological parameters,
opportunistic infections, or iatrogenic
complications arising from chemotherapy.
Acute lymphocytic leukemia (ALL)
• Is a malignant clonal disorder of the bone
marrow lymphopoietic precursor cells.
• In ALL, progressive medullary and
extramedullary accumulations of lymphoblasts
are present that lack the potential for
differentiation and maturation.
• An inhibition of the normal development of
hematopoietic cell elements occurs.
Acute lymphocytic leukemia (ALL)
• The clinical presentation is dominated by
progressive weakness and fatigue
secondary to anemia,
infection secondary to leukopenia, and
bleeding secondary to thrombocytopenia.
• When 50% of the bone marrow is replaced,
then peripheral blood cytopenias are
observed.
Acute lymphoblastic leukemia
(ALL)
• Is the most common type of leukemia in young children.
• This disease also affects adults, especially those aged 65
and older.
• Standard treatments involve chemotherapy and
radiotherapy.
• The survival rates vary by age: 85% in children and 50% in
adults.
• Subtypes include:
 precursor B acute lymphoblastic leukemia,
 precursor T acute lymphoblastic leukemia,
 Burkitt's leukemia, and
 acute biphenotypic leukemia
A Wright's stained bone marrow aspirate smear
from a patient with precursor B-cell acute
lymphoblastic leukemia
Acute myelogenous leukemia
(AML)
• Is a group of neoplastic disorders of the
hematopoietic precursor cells of the bone
marrow.
• AML is subdivided by the FrenchAmerican-British system into 6 categories
depending on the morphology.
• AML is not a disorder of rapidly
proliferating neoplastic cells
Acute myelogenous leukemia
(AML)
• The time for one cell division is prolonged
with respect to that of normal bone marrow
blast cells.
• A failure of maturation of the neoplastic cell
clone exists.
• The bone marrow is gradually replaced by
blast cells.
• Therefore, the most important complications are
progressive anemia, leukopenia, and
thrombocytopenia.
Acute myelogenous leukemia
(AML)
• Occurs more commonly in adults than in
children, and
• more commonly in men than women.
• AML is treated with chemotherapy.
• The five-year survival rate is 40%.
• Subtypes of AML include;
 acute promyelocytic leukemia,
acute myeloblastic leukemia, and
 acute megakaryoblastic leukemia
acute myeloid leukemia bone marrow
showing immature leukemia cells
Chronic myelogenous leukemia
(CML)
• is characterized by an uncontrolled
proliferation of granulocytes.
• An accompanying proliferation of erythroid cells
and megakaryocytes is usually present.
• Many patients are asymptomatic but may
present with
 splenomegaly,
 weight loss,
 malaise,
 bleeding, or
 thrombosis
Chronic myelogenous leukemia
(CML)
• CML is characterized by a balanced
reciprocal translocation between the long
arms of chromosomes 9 and 22
[t(9;22)(q34;q11.2)] that occurs in about 90%
to 95% of cases.
• This translocation results in the juxtaposition
of the c-abl proto-oncogene from
chromosome 9 with a portion of the bcr
gene located on chromosome 22, thereby
producing a novel bcr/abl fusion gene.
(CML)
• The gene product results in an 8.5-kb
mRNA transcript that generates a 210-kd
bcr/abl fusion protein having abnormal
tyrosine kinase activity.
• Through phosphorylation, this enzyme
may activate different signal transduction
pathways that may result in increased
proliferation and decreased apoptosis
(programmed cell death) of hematopoietic
cells
Leukemia Chronic Myeloid
Chronic myeloid leukemia
Chronic Myelogenous Leukemia
Chronic lymphocytic leukemia
(CLL)
• Represents a monoclonal expansion of
lymphocytes.
• In 95% of cases, CLL is a predominantly
malignant clonal disorder of B lymphocytes.
• The remainder is secondary to a T-cell clone.
• The neoplastic cell is a hypoproliferative,
immunologically incompetent small
lymphocyte
Chronic lymphocytic leukemia
(CLL)
• There is primary involvement of the bone marrow
and secondary release into the peripheral blood.
• The recirculating lymphocytes selectively infiltrate
the lymph nodes, the spleen, and the liver.
• Most patients are asymptomatic at diagnosis.
• As the disease progresses,
 lymphadenopathy,
 splenomegaly, and
 hepatomegaly develop.
• A secondary immune deficiency with
hypogammaglobulinemia exists
Chronic lymphocytic leukemia
(CLL)
• most often affects adults over the age of 55.
• It sometimes occurs in younger adults, but it
almost never affects children.
• Two-thirds of affected people are men.
• The five-year survival rate is 75%.
• It is incurable, but there are many effective
treatments.
• One subtype is B-cell prolymphocytic leukemia,
a more aggressive disease
Chronic lymphocytic leukemia
(CLL)
Chronic lymphocytic leukemia (CLL), on the other hand,
does not usually form tumor masses. . increased proportion
of large or atypical lymphocytes in the blood
.
B-cell chronic lymphocytic leukemia
Causes
• No single known cause for any of the different
types of leukemia exists.
• The known causes, which are not generally
factors within the control of the average person,
account for relatively few cases
• Among adults, the known causes are natural
and artificial
ionizing radiation,
Causes
a few viruses such as human Tlymphotropic virus(HTLV-1), cause adult Tcell leukemia and
some chemicals, notably benzene and
alkylating chemotherapy agents for
previous malignancies.
 Use of tobacco is associated with a small
increase in the risk of developing acute
myeloid leukemia in adults.
Causes
• Some people have a genetic predisposition
towards developing leukemia
• people with chromosomal abnormalities or
certain other genetic conditions have a
greater risk of leukemia.
For example, people with Down syndrome
have a significantly increased risk of
developing forms of acute leukemia
(especially acute myeloid leukemia), and
Fanconi anemia is a risk factor for
developing acute myeloid leukemia.
EPIDEMIOLOGY:
 Age
• Most childhood leukemias are acute.
• ALL is the most common malignancy in
children, especially affecting those aged 2-10
years.
• ALL is seen in only 20% of adult acute
leukemias and behaves more aggressively
than the childhood type.
• AML constitutes 15-20% of acute leukemias
in children.
EPIDEMIOLOGY:
 Age
• Incidence of AML increases with age; in
persons younger than 65 years, the
incidence is 1.3, and in persons older than
65 years, the incidence is 12.2.
• CML constitutes less than 5% of childhood
leukemias.
• The incidence of CML increases slowly with
age until the middle 40s, when the incidence
starts to rise rapidly.
EPIDEMIOLOGY:
• Sex
• Generally is more common in males and than
females.
• The breakdown of new cases of leukemia by
gender and category is as follows:
• CLL: male > females
• CML: male > females
• ALL: males> females; childhood ALL
demonstrates a notable male predominance.
• AML: males > females
Mortality/Morbidity
• When all leukemias are lumped together,
the global 5-year survival is 20%.
• In developed countries, 31% survive for 5
or more years, compared with 15% in
developing countries.
• This underscores the lack of access to
high-tech treatment in the developing
world
Diagnosis
• Diagnosis is usually based on repeated
complete blood counts and
• a bone marrow examination following
observations of the symptoms,
• A lymph node biopsy can be performed
as well in order to diagnose certain types
of leukemia in certain situations
Treatment
• Most forms of leukemia are treated with
pharmaceutical medication, typically
combined into a multi-drug chemotherapy
regimen.
• Some are also treated with radiation
therapy.
• In some cases, a bone marrow transplant is
useful