leukemias.ppt

About the Disease
 Leukemia, lymphoma and myeloma are
cancers that originate in the bone marrow
(leukemia & myeloma) or in lymphatic tissues
(lymphoma).

Different Types of Blood Cancers
 Leukemia
 Non-Hodgkin Lymphoma
 Hodgkin Lymphoma
 Myeloma
 Myelodysplastic Syndromes

What is Leukemia?
 Leukemia is cancer
found in the blood cells
 There are many types
of Leukemia
 They are classified by
how quickly they
progress and what type
of cell they affect
 Leukemia is causes
when there is an
imbalance of healthy
unhealthy blood cells in
the body
 This occur when one
cell awry and the body
begins to produce large
numbers of this cell

What Is Leukemia?
 Cancer of the white blood cells
 Acute or Chronic
 Affects ability to produce normal blood cells
 Bone marrow makes abnormally large
number of immature white blood cells called
blasts

What is Leukemia
 Greek word which means “white blood”
 Leukemia is when cells spread rapidly and destroy
living tissue.
 It grows/invades the bone marrow which is the
factory of blood and replaces normal blood elements
with cancer cells.
 Cancer cells replace all bone marrow cells which
causes infection and bleeding problems.
 Leukemia is basically white blood cells that don’t
work well and cause trouble.

Continued
 Millions of immature and useless white blood cells
are produced which makes it harder to kill cancer
cells and preserve the good/healthy ones.
 Leukemia causes change in cells, DNA, and gene.
 If the blood matches with donator then you are
curried.
 Bone marrow is spongy tissue that fills in the center
core of bone.
 There are 4 different types of Leukemia.

Types of Leukemia
 Based on how quickly the
disease develops it is
classified as either acute or
chronic
 In Acute Leukemia the
white blood cells tend to
develop more rapidly and
very immature
 In Chronic Leukemia the
cells tend to develop more
slowly
 They are also classified by
which type of white bloods
cells are affected
 If the lymphoid cells are
affected the disease is
referred to as
Lymphocytic Leukemia
 If the myeloid cells are
affected it is called
Myelongenous Leukemia

Types of Leukemia
 Acute lymphoblastic Leukemia (ALL)
 Acute myeloblastic Leukemia (AML)
 Chronic lymphocyte Leukemia (CLL)
 Chronic myeloid Leukemia (CML)

Demographics of Leukemia
Patients (2001 Data)
ALL
11%
CLL
26%
AML
31%
CML
15%
others
17%
Total Reported Cases = 31,500
Sources from Leukemia, Lyphoma,
Myeloma Facts 2001
CLL=Chronic
Lymphocytic
ALL=Acute
Lymphocytic
CML=Chronic
Mylogenous
AML=Acute
Mylogenous

Chronic and Acute
Chronic Leukemia:
 Progress slowly (runs a slow course)
 Not immediately fatal.
Acute Leukemia:
 Progress rapidly (runs a fast course)
 Life expectancy short without treatment.

Lymphocyte and Myeloid
Lymphocyte:
 Increase in white blood cells produced in lymph
nodes and bone marrow.
 Strikes without any warning.
Myeloid:
 Increase in white blood cells produced exclusively in
the bone marrow.
 Strikes without any warning.

Acute Myeloid Leukemia
(AML):
 Mixed group of disease
 It means “marrow like” and in this context it
simply means arising from developing blood
cells.
 This type of leukemia runs a rapid course.

Acute Lymphoblast Leukemia
(ALL):
 Group of different diseases
 A complexity of which is still trying to be
unraveled
 Reached a point where not all are being
treated the same.
 This type of Leukemia runs a rapid course.

Chronic Myeloid Leukemia
(CML):
 Characterized by increased production of
granulocytes in the bone marrow.
 Usually associated with a specific
chromosomal abnormality called the
Philadelphia chromosome
 Progresses slowly

Chronic Lymphocyte Leukemia
(CLL):
 This type of cancer is so rare it could be said
not to arise at all in the first two decades of
life.
 Starts of in the Bone marrow
 This type of cancer runs a slow course giving
more time to live.

Risk Factors
 As of now we do not know
the exact cause of Leukemia
 Exposure to these have been
identified as risk factors
 High energy radiation
 Some genetic syndromes
 People working with chemical
benzene for a long period of
time

Causes
 High level radiation/toxin exposure
 Viruses
 Genes
 Chemicals
 Mostly unknown
 Can’t be caught

Development of Leukemia in the
Bloodstream
Stage 1- Normal Stage 2- Symptoms Stage 3- Diagnosis
Stage 4- Worsening
Stage 5a- Anemia
Stage 5b- Infection
Legend
White Cell
Red Cell
Platelet
Blast
Germ Sources from Leukemia, by D. Newton and D. Siegel

Effects On the Body
 Attacks the immune system
 Infections
 Anemia
 Weakness
 No more regular white blood cells, red blood cells,
and platelets
 Blasts clog blood stream and bone marrow

Symptoms
 When there are excessive white blood cells -
-> Infections
 When there are few red blood cells:
Paleness --> Anemia
 When there are few platelets --> Excessive
bleeding

Signs Of Leukemia
Most of the symptoms of leukemia are similar to those of a
common illness such as the flu. The symptoms will vary
according to the type of leukemia.
 Tired
 Frequent infections
 Easy bruising or bleeding
 Bone tenderness
 Headache
 Enlarged lymph nodes
 Low red blood count
 Pale skin
 Poor appetite

Tests For Diagnosis
 Finger prick
 Blood sample
 Blood dye
 Bone marrow sample
 Spinal Tap/Lumbar Puncture

Diagnosis
 As immature cells increase in the body leads to lower
amounts of red blood cells and platelet cells
 The low amounts of red blood cells cause patient to be
tired and pale
 Low amounts of platelet cells cause the patient to easily
bruise or bleed
 During a physical exam the doctor detects swollen spleen,
liver, or lymph nodes
 Then there is a blood test conducted to see if it is leukemia
 The type of Leukemia is determined after bone marrow is
extracted and tested

Diagnosis
 Most commonly leukemia is diagnosed by a
blood test to count the number of red cells,
white cells and platelets. A biopsy of the
bone marrow may also be performed

Pictures Of Blood
Normal human blood
White Cell Red Cell
Platelet
Blood with leukemia
Blasts
Red Cell
Platelet
White Cell
Sources from Arginine.umdnj.edu
Sources from beyond2000.com

Diagnosis
Requires all of the following diagnostic
components:
a) Documentation of bone marrow
infiltration
b) Myeloid origin of the leukemic cells
c) FAB/WHO classification of the
leukemia
d) Karyotypic analysis

Differential Diagnosis
 chronic myelogenous leukemia
 other myeloproliferative disorders
 reactive leukocytosis: leukemoid reaction
 acute leukemia

Philadelphia Chromosome
t(9;22)(q34;q11)

BCR-ABL p210 Fusion Protein
Activity
 Higher tyrosine kinase activity.
– Increases progenitor cells, reduces the pool of
stem cells. Semin Hematol 1988;25:1-19.
– Defective cytoadherence. Hematol Oncol Clin North
Am 1988;12:1-29.
– Suppression of apoptosis. Blood 1994;83:1575-85.

BCR-ABL p210 Fusion Protein
Evidence of its role in CML
 In vitro: cause factor-independent,
leukemogenic cell growth in hematopoietic
cell lines.
 In vivo: generate in mice CML-like syndrome.
Science 1990;247:824-30.

FAB Classifications
M0: minimally differentiated
M1: without maturation
M2: with maturation. May have t(8;21) translocation.
M3: promyelocytic. Good prognosis. Can be associated
w/ t(15;17).
M4: myelomonocytic; assoc. w/ t(16;16) or
inv(16)(p13q22).
M5: monoblastic
M6: erythroleukemia
M7: megakaryoblastic. Poor overall survival.

Clinical Course
 Median survival: 3.5~8 yr.
 Chronic phase: 3~4 yr.
 Accelerated phase (15%): 3~6 mo, then enters acute
phase.
 Acute phase (blast crisis), 25% in each year, findings:
blasts > 30%, cytogenetic changes other than Ph
chromosome, progression likes acute leukemia. 70%
enters AML, 30% ALL.

Prognosis
“Good risk”: favorable karyotype, including
t(8;21), t(15;17), inv(16)/t(16;16)/del(16q)
or FAB subtype M3
“Poor risk”: adverse karyotype or resistant
disease after first course of chemo (i.e. >15%
blasts in post-tx bone marrow bx)
5-yr survival for good, standard, and poor risk
patients 70, 48, and 15% respectively.
Relapse rates are 33, 50, and 78%
respectively.

Treatment
 As of yet there is no
cure for Leukemia
 Many advances have
been made in the past
couple years
 The survival rate of
children with Acute
Lymphocytic is around
82%
Treatments include:
 Chemotherapy
 Radiotherapy
 Immunotherapy
 Bone marrow transplant

Research
 New drugs
 Cord blood and planceta

Treatment
 Depending on the type of cancer treatments may
vary. Treatments of leukemia may include
chemotherapy, radiation therapy, or bone
marrow transplant. They also treat leukemia
patients with the infusion of healthy blood cells
and platelets. During and after the treatment
blood counts are done to see if the patient is
being controlled or in remission.

Treatments
 Blood and marrow stem cell transplantation.
 Research.
 Development of new drugs.
 Immunotherapy.
 Vaccines.
 Reversal of multidrug resistance.
 Gene therapy.

Management (1)
 Chronic phase
– Hydroxyurea or busulfan, relieves symptoms and
control of disease.
– Interferon-a: 20% cytogenetic response,
prolongation of survival. . It can gain 20 more
months survival than C/T. This advantage must be
weighed against its significant side effects.

Management (2)
BMT or PBSCT
 Allogeneic bone marrow transplantation in
the chronic phase is the only therapy known
to cure CML
5YS > 50%, relapse < 20%, 20~40% BMT
related death in the first year.
 It should be done as soon as possible for
patients
– Chronic phase.
– <50 years old.
– Has an HLA-identical sibling.

Management (3)
STI571
 STI 571:Inhibitors of the BCR-ABL fusion proteins
(tyrosine kinase)
 After six months of therapy with Glivec (STI571), preliminary findings
showed that half of 290 patients tested were improving. They had
what's known as a cytogenic remission -- a reduction in the
'Philadelphia Chromosome' which causes the disease.
 "In these patients we found a very high response rate, there was some
response seen in 91 percent of the patients," said Dr. Talpaz of the
M.D. Anderson Cancer Center. "Some of the patients returned to the
chronic phase of the disease."

Allogeneic Stem Cell Transplantation
 eradicates of the marrow cells (marrow-
ablating C/T or R/T)
 implantation of allogeneic stem cells
 homing of the stem cells to the marrow cavity
 growth of the stem cells and recovery of the
blood cells

Complications of SCT
 rejection, graft failure
 graft-versus-host disease
 infection
 VOD
 obliterative bronchiolitis
 sepsis
 relapse of disease

GVHD
(Graft versus Host Disease)
 Immunologic reaction of donor lymphocytes
to “foreign” antigens present on the surface
of host cells
 “foreign” antigens:
– HLA antigens
– “minor” antigens not detected by current typing
techniques

Acute GVHD (1) incidence
 Within the first 3 months after BMT
 20~50% of HLA-identical, 80% of HLA non-
identical recipients
 incidence increases with
– patient age
– degree of HLA disparity

Acute GVHD (2)manifestations
 Histology: lymphocytic infiltration of the epidermis
and GI tract
 fever
 dermatitis: diffuse macular dermatitis, bullas,
desquamation
 enteritis: cramping abdominal pain, watery to bloody
diarrhea
 hepatitis: jaundice, cholestasis, hepatocellular
necrosis
 infection: frequently related to mortality
 hyperacute GVHD (no prophylaxis): 7 days after BMT:
exfoliative dermatitis, shock, hyperpyrexia

Chronic GVHD (1) incidence
 develops > 3 months after BMT
 20~50% of allografts, usually following acute
GVHD
 20~30% develops de novo, without prior
acute GVHD

Chronic GVHD (2)
manifestations like collagen diseases
 skin: pigmentation, sclerosis
 mucosa: lichenoid oral plaque, esophagitis,
polyserositis, oral and eye sicca syndrome
 liver: elevated ALP and GOT in 90% cases
 chronic wasting due to anorexia
 chronic pulmonary disease: 10~20% (diffuse interstitial
pnuemonitis and obliterative bronchiloitis)
 death usually caused by infection, low mortality
related to de novo onset & less tissue involvement.

Blast Crisis
 30% ALL, 70% AML
 Treatment likes de novo acute leukemia with poor
success.
 Chance of achieving remission is possible in ALL,
which may last 4~8 months, but low in AML.
 Survival is usually 2~4 months.

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