Leukemias

The development of Leukemia

uncontrolled and accelerated production of haematopoietic stem
cell, progenitors, or mature blood cells which results in incomplete
or defective cell maturation

Acute Lymphocytic Leukemia (ALL)

Acute Mylogenous Leukemia (AML)
Chronic Lymphocytic Leukemia (CLL)
Chronic Mylogenous Leukemia (CML)

Copyright, 1996 © Dale Carnegie & Associates, Inc.

 Demographics of
Leukemia Patients
CLL=Chronic
Lymphocytic
ALL=Acute
Lymphocytic
CML=Chronic
Mylogenous
AML=Acute
Mylogenous
Stem cells and growth factors in haematopoietic
cell development.

• page 1003
Hematopoietic stem cells give rise to two major
progenitor cell lineages, myeloid and lymphoid
progenitors
 ALL
naïve
aïve

B-lymphocytes
Plasma
Lymphoid cells
progenitor T-lymphocytes

AML Myeloproliferative
lr lif r tii rr disorders
Hematopoietic Myeloid Neutrophils
stem cell progenitor

Eosinophils

Basophils

Monocytes

Platelets

Red cells
 Acute leukemia

• is characterized by a rapid increase

in the numbers of immature blood cells. Crowding due to such cells
makes the bone marrow unable to produce healthy blood cells.
Immediate treatment is required in acute leukemia due to the rapid
progression and accumulation of the malignant cells, which then spill
over into the bloodstream and spread to other organs of the body. Acute
forms of leukemia are the most common forms of leukemia in children.
 Chronic leukemia

• is characterized by the excessive build up of relatively

mature, but still abnormal, white blood cells. Typically
taking months or years to progress, the cells are produced
at a much higher rate than normal cells, resulting in many
abnormal white blood cells in the blood. Whereas acute
leukemia must be treated immediately, chronic forms are
sometimes monitored for some time before treatment to
ensure maximum effectiveness of therapy. Chronic
leukemia mostly occurs in older people, but can
theoretically occur in any age group.
 Main Signs and symptoms
• 1. Hyperplasia or hyperproliferation of
affected cell - uncontrolled proliferation of
malignant cells and their spreading (in bone
marrow, peripheral blood and organ
infiltration of spleen (nausea or feeling of
fullness due to an enlarged liver and
spleen), lymph nodes, skin, gastrointestinal
tract, central nervous system (neurological
symptoms (headaches)).
 Main Signs and symptom
• 2. Malignant cells replace normal bone marrow elements
leading to
• a) anemia (clinical manifestation - dyspnea and pallor),
• b) thrombocytopenia (people with leukemia may easily
become bruised, bleed excessively, or develop pinprick
bleeds (petechiae),
• c) neutropenia (clinical manifestation - frequent infection,
ranging from infected tonsils, sores in the mouth, or
diarrhea to life-threatening pneumonia or opportunistic
infections),
 Main Signs and symptom
• 3. Nonspecific symptoms of intoxication (feeling
sick, such as having fevers, chills, night sweats and
other flu-like symptoms, or feeling fatigued),
• 4. Metabolic and Electrolyte Abnormalities
 Pictures Of Blood
Platelet
Red Cell Blasts
Platelet White Cell

White Cell Red Cell

Normal human blood Blood with leukemia

 Development of Leukemia in the Bloodstream

Stage 1- Normal Stage 2- Symptoms Stage 3- Diagnosis

Legend
White Cell Stage 5a- Anemia

Red Cell
Platelet Stage 4- Worsening
Blast
Germ
Stage 5b-
Infection
 DEFINITION
Acute leukemias are clonal malignant
hematopoietic disorders resulting from genetic
alterations in normal hematopoietic stem cells.
These alterations disrupt normal
differentiation and/or cause excessive
proliferation of abnormal immature
“leukemic” cells or “blasts.” As the disease
progresses, leukemic cells accumulate in the
bone marrow, blood, and organs, displacing
normal progenitor cells and suppressing normal
hematopoiesis.
FAB Classification of ALL
 FAB Classification of AML
Percentage of
Type Name Cytogenetics
adults with AML
acute myeloblastic leukemia,
M0 5%
minimally differentiated
acute myeloblastic leukemia,
M1 15%
without maturation
acute myeloblastic leukemia,
M2 t(8;21)(q22;q22), t(6;9) 25%
with granulocytic maturation
promyelocytic, or acute
M3 t(15;17) 10%
promyelocytic leukemia (APL)
M4 acute myelomonocytic leukemia inv(16)(p13q22), del(16q) 20%
myelomonocytic together with
M4eo bone marrow eosinophilia inv(16), t(16;16) 5%

acute monoblastic
M5 leukemia (M5a) or acute del (11q), t(9;11), t(11;19) 10%
monocytic leukemia (M5b)
acute erythroid leukemias,
including erythroleukemia
M6 5%
(M6a) and very rare pure
erythroid leukemia (M6b)
acute megakaryoblastic
M7 t(1;22) 5%
leukemia
 Clinical presentation
• Common symptoms of both acute myeloid leukemia
(AML) and acute lymphoblastic leukemia (ALL) are a
reflection of bone marrow failure and include fatigue,
bruising or bleeding, fever, and infection.
o Pancytopenia:
• WBCinfection.
• Hb anemia.
• platelets bleeding.
o Organ infiltration:
• Lymphadenopathy.
• Splenomegally.
• Hepatomegally.
• CNS: 5-10% of patient with ALL
 Investigations: • CBC:
o 60% of pts have an elevated WBC. o
Most are anemic
o Most are thrombocytopenic
o 90% have blast in the periphral blood film. •
electrolytes:
o Hypo/hyper kalemia o
Hypomagnesimia
o hyperphosphatemia •
Hypermetabolism:
o LDH.
o uric acid. •
DIC:
o Most common with promyelocytic leukemia, small% monocytic
• Bone marrow biopsy and aspirate :
30%or more
o leukemia of all nucleated cells are blast. •
& ALL
Radiology:
o CXR: mediastinal mass(T-cell ALL)
o Osteopenia or lytic lesion 50% of patients with ALL.(itractable pain).
Acute leukemia diagnostic algorithm.
Lymphoblast/myeloblast
Acute lymphoblastic leukemia ALL-L1
Acute lymphoblastic leukemia ALL-L1
Acute lymphocytic leukemia ALL-L2
Acute lymphocytic leukemia ALL-L3
Acute lymphocytic leukemia ALL-L3
Acute myeloid leukemia AML-M0
Acute myeloid leukemia AML-M1
Acute myeloid leukemia AML-M2
Acute myeloid leukemia AML-M2
+ peroxidase
Acute myeloid leukemia AML-M3
Acute myeloid leukemia AML-M3
hypogranular
Acute myeloid leukemia AML-M4
Acute myeloid leukemia AML-M5
Acute myeloid leukemia AML-M6
Acute myeloid leukemia AML-M7
 Management: • A-
Supportive measure:
-isolation in positive laminer flux room
-insertion of central line
-family and patient support by permanent social
worker
-AlKaline diuresis to prevent tumor lysis syndrome
-oropharynx/GIT decontamination to prevent

fungal infectionfor infection

-IV antibiotics
-Blood transfusion if anemia and thrombocytopenia.
 Cont:
• Special consideration: CNS:
-neuroprophylaxis:
- meningeal infiltration:
by intrathecal chemotherapy, high dose
systemic MTX or Aracytine. OR
cerebrospinal irradiation

Testis: by i trat ecal c e ot erapy, ig dose

syste icor racyti e.
orchidectomy/radiotherapy if testis involvement.
cerebrospi al irradiatio
Prognosis in ALL

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 Prognosis in AML

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 Chronic lymphocytic leukemia (1)
• Is characterised by the accumulation of nonproliferating mature-
appearing lymphocytes in the blood, marrow, lymph nodes, and
spleen
• In most cases, the cells are monoclonal B lymphocytes that are
CD5+
• T cell CLL can occur rarely
 CLINICAL
•Localized or generalized
lymphadenopathy
oSplenomegaly (30-40% of cases)
oHepatomegaly (20% of cases)
•Petechiae
•Pallor
lymphadenopathy
Chronic lymphocytic
leukemia
Hairy-cell leukemia
Smudge Cells
Smudge Cells
 The diagnostic criteria for CLL

1) A peripheral blood lymphocyte count of greater than 5

G/L, with less than 55% of the cells being atypical
2) The cell should have the presence of Bcell-specific
differentiation antigens (CD19, CD20, and CD24) and be
CD5(+)
3) A bone marrow aspirates showing greater than 30%
lymphocytes
 Investigations
• Pretreatment studies of patients with CLL should include
examination of:
o complete blood count
o peripheral blood smear
o reticulocyte count
o Coomb’s test
o renal and liver function tests
o serum protein electrophoresis
o immunoglobulin levels o plasma 2
microglobulin level
• If available immunophenotyping should be carried
out to confirm the diagnosis
• Bone marrow biopsy and cytogenetic analysis is not
routinely performed in CLL
 Staging (1)
• Rai Classification for CLL
o 0 - lymphocytosis (>5 G/L)
o I - lymphocytosis + lymphadenopathy
o II - lymphocytosis + splenomegaly +/-
lymphadenopathy
o III - lymphocytosis + anemia (Hb <11g%) +/-
lymphadenopathy or splenomegaly
o IV - lymphocytosis + thrombocytophenia (Plt <100G/L)
+/- anemia +/-lymphadenopathy +/-splenomegaly
 Staging (2)
• Binet Classification for CLL
o A. < 3 involved areas, Hb > 10g%, Plt > 100G/L o B.
> 3 involved areas, Hb > 10g%, Plt > 100G/L o C. - any
number of involved areas, Hb < 10g%,
Plt < 100G/L
 Treatment
• Treatment is reserved for patients with low- or
intermediate risk disease who are symptomatic
or have progressive disease (increasing
organomegaly or lymphocyte doubling time of
less than 12 months) and patients with high -risk
disease
Alkylatingphamide)
o cyclopho agents (chlorambucil,
o Nucleosides analogs (cladribine, fludarabine)
o Biological response modifiers
o Monoclonal antibodies o Bone
marrow transplantation
o And systemic complications requiring therapy •
antibiotics
• immunoglobulin •
steroids
• blood products
 Chronic myelogenous
leukemia
(CML) is a myeloproliferative
disorder characterized by
increased proliferation of the
granulocytic cell line without the
loss of their capacity to
differentiate. Consequently, the
peripheral blood cell profile shows
an increased number of
granulocytes and their immature
precursors, including occasional
blast cells.
 Leukemia
• Chronic Myelogenous
Leukemia
o Cancer of the granulocytes or
monocytes, compared
to leukocytes in
lymphocytic leukemia
o Comprises about 14% of all
adult leukemias
o Males slightly higher than
females
o One of the first cancers to have a
specific genetic link
to a chromosomal mutation
identified for the disease
• Philadelphia
Chromosome
HEPATOSPLENOMEGALY
chronic phase accelerated phase
accelerated phase blast crisis
blast crisis
• A small number of patients
show some resistance to
Imatanib
• The BRC-ABL transcript has the
ability to mutate and thus make
imatinib ineffective
• Imatinib binds to the closed
conformation and BRC-ABL can
mutate to the open conformation
and thus makes imatanib
ineffective
• Two 2nd generation TKIs have
proven to be more potent and
are in trials to determine
effectiveness against
resistance to imatanib
Treatment Algorithm