Leukemia 2

KEGANASAN HEMATOLOGI
HEMATOPOESIS
TAHAPAN PEMERIKSAAN
KEGANASAN HEMATOLOGI
• COMPLETE BLOOD COUNT (CBC )
– LEKOSIT : >> / N / <<
– HB : <
– TROMBOSIT : <
• BLOOD SMEAR : MORPHOLOGI

– BLAST > 20%
– NORMOSITIK NORMOKROMIK ANEMIA
– TROMBOSIT : <
BMP
BMP (BONE MARROW
PUNCTION)
• MAY GRUNDWALD STAIN
• CITOKIMIA:
– PAS  (+) Lymphoblast
– SUDAN BLACK  (+) Myeloblast
• MPO
• IMMUNOPHENOTYPE 
FLOWCITOMETRY
• CITO GENETIC
Acute Leukemia:
Essentials:
• Short course of symptoms
• Fatigue, fever, easy bruising, bleeding
• Cytopenias - or pancytopenia
• More than 20% blasts in bone marrow
• Blasts in peripheral blood in 90% cases

Acute Myeloid Leukemia (AML):
Etiology:
• Genetic
• Radiation
• Toxic chemical exposure
• Medication (Alkylating-agents, Topoisomerase-II

inibitors, Chloramphenicol, Phenylbutazone,
Chloroquine, and Methoxypsoralen)
Symptoms:
• Nonspecific
• Most related to anemia, leukocytosis, leukopenia,

leukocyte dysfunction, or thrombocytopenia
• Symptoms usually present for 3 months or more

before diagnosis is made
Other Common Sx:
• Bone pain
• Lymphadenopathy
• Non-specific cough
• Headaches
• Excessive diaphoresis
• Symptoms secondary to mass lesions (granulocytic
sarcoma)
Physical Findings:
• Fever
• Splenomegaly
• Sternal tenderness
• Multiple bruises
• Bleeding (gingivae most common)
• Unexplained infections
• GI bleed
• Pulmonary, intracranial, and retinal hemorrhage
Laboratory and Radiographic Work-up:
• CBC with manual differential

• Uric Acid level
• Clotting studies (PT, PTT, D-dimer, fibrinogen)
• Bone marrow aspirate and biopsy
• Chest xray
• Echocardiogram
Hematological Findings:
• Anemia (normochromic, normocytic)
• Leukocytosis (median = 15,000)
• Thrombocytopenia (< 100,000)

Morphology and Cytology:
• > 20% myeloblasts in blood and/or bone marrow
• Auer Rods (cytoplasmic granules)
• Positive myeloperoxidase reaction in > 3% blasts

AML Histology
AML Histology
Classification/Subtypes:
• French-American-British Classification
· eight major subtypes
· based on morphology and cytochemistry
• World Health Organization Classification

· based on molecular, morphologic, and clinical features
Classification of AML
Subtype FAB Type Morphology Cytogenetic Abnl
AML w/o maturation M0 no azurophil granules -
AML M1 few Aeur rods del(5); del(7); +8

maturation beyond
promyelocytes; Auer
AML w/ differentiation M2 rods t(8:21) t(6:9)
hypergranular
promyelocytes; Auer
Acute Promyelocitic Leukemia M3 rods t(15:17)
> 20% monocytes;
monocytoid cells in inv(16) del(16) t(16:16)
Acute Myelomonocytic Leukemia M4 blood t(4:11)
monoblastic;
Acute Monocytic Leukemia M5 promonocytic t(9:11) t(10:11)
predominance of
erythroblasts;
Acute Erythroleukemia M6 dyserythropoiesis -
dry' aspirate; biopsy

Acute Megakaryocytic Leukemia M7 dysplastic with blasts -
Prognostic Factors:
• Age at diagnosis
• Comorbidities (acute vs chronic)
• Chromosomal findings
• Symptomatic interval preceding diagnosis
• Presenting Leukocyte count
• Circulating myeloblast count
• FAB classification
• Morphologic characteristics of the leukemic cell
Acute Lymphoid Leukemia (ALL):
Incidence:
• Approximately 3,000 new cases per year
• Mostly affects children, accounts for 2/3 of

childhood leukemia (peak age 4 years)
• Comprises less than 20% of leukemia in young

adults
• May be B-cell, T-cell, or null-type (non-B, non-T

cell)
Etiology:
• Uncertain, but several proposed linkages:

·Genetic - Philadelphia chromosome
·Viral infection (EBV, HIV)
·Exposure to high energy radiation (T-cell ALL)
·Toxic chemical exposure
·Smoking
Physical Findings:
• Fever
• Splenomegaly and/or hepatomegaly
• Lymphadenopathy
• Petechiae

• Chemistry studies to check for organ dysfunction
• Bone marrow aspirate and biopsy
• Genetic/Immunological studies
• Lumbar puncture
• WBC < 5,000 (or > 25,000)

ALL Histology
ALL Histology
Classification of ALL
Immunologic Subtype FAB Type % of Cases Cytogenetic Abnl
Pre-B cell ALL L1, L2 75 t(9:22) t(4:11) t(1:19)
T-cell ALL L1, L2 20 14q11 or 7q34
B-cell ALL L3 5 t(8:14) t(8:22) t(2:8)
L1 - 85% of childhood ALL

L2 - Majority of adult ALL
L3 - Includes Burkitt’s. < 5% of ALL
Prognostic Factors:
• Adult vs Childhood type

• Morphology (FAB class)
• Chromosomal findings
• WBC > 50,000
• B-cell type worse than T-cell type
• Lymphadenopathy
• Hepatosplenomegaly
Acute Leukemia:
After Induction Chemotherapy:
• Bone marrow biopsy is obtained
• If >5% of blasts with >20% cellularity, then

retreatment necessary.
• Stem cell transplant may be necessary if

retreatment fails.
Chronic Leukemia:
Essentials:
• Most are asymptomatic at presentation
• Strikingly elevated WBC
• Marked left-shift
• Philadelphia chromosome
• Splenomegaly typical
• Lymphocytosis
Chronic Myeloid Leukemia (CML):
Pathophysiology:
• Philadelphia chromosome (9:22) in up to 95%
• BCR-ABL protein junction

Common Sx:
Note: approximately 70% of patients are asymptomatic at the
time of diagnosis
• Lethargy
• Weight loss
• Increasing abdominal girth
• Easy bruising or bleeding
• Excessive diaphoresis
Physical Findings:
• Fever
• Splenomegaly and hepatomegaly
• Bruising
• Bleeding (gingivae most common)

• Serum Vitamin B12 and B12 binding capacity
• Leukocyte alkaline phosphatase (decreased)
• Uric acid level
• Chromosomal testing - Philadelphia chromosome
• Bone marrow biopsy
• Basophilia

CML Histology
CML Histology
Three Phases:
• Chronic phase: 3-5 years. Current treatment is with

alpha-interferon. Young patients should undergo BMT.
• Accelerated phase: New nonrandom cytogenic

abnormalities in up to 80% of patients. Difficult to control.
Development of myelofibrosis. Elevated leukocyte counts.
Lasts several months before becoming blastic.
• Blast phase: > 30% blasts in blood or marrow. Treatment

with chemotherapy similar to acute leukemia. Some patients
go into remission with treatment, but it is short lived.
Prognostic Factors:
• Age at diagnosis
• Splenomegaly
• Blasts > 5% in blood or marrow at diagnosis
• Basophilia > 7%
• Platelets > 700,000
Chronic Lymphoid Leukemia (CLL):
Incidence:
• 2 new cases per 100,000 people per year
• Comprises 30% of all cases of leukemia
• Most common lymphoid leukemia
• Almost exclusively due to B-cell clonal expansion
• More common in men
• Most common in individuals < 50 years
Etiology:
• Uncertain, several proposed linkages:

·Genetic
·Viral infection (EBV, HIV) - Burkitt’s
·Exposure to high energy radiation (T-cell ALL)
·Toxic chemical exposure
·Smoking
Physical Findings:
• Fever
• Splenomegaly and/or hepatomegaly
• Lymphadenopathy
• Bleeding gingivae

• Peripheral smear
• Flow cytometry
• Chemistry studies to check for organ dysfunction
• Lymph node biopsy
• Increased number of lymphocytes on smear

·smudge cells
• B-cells with CD 19 and CD 5 on flow cytometry
• Small lymphocitic lymphoma present in histology

of nodal biopsy
CLL Histology
CLL Histology
RAI Classification of CLL
Stage Risk Clinical/Morphological Features
0 Low Lymphocytosis alone
I Intermediate Lymphocytosis with lymphadenopathy
Lymphocytosis with lymphadenopathy

II Intermediate and splenomegaly or hepatomegaly
III High Lymphocytosis with anemia
Lymphocytosis with anemia and

IV High thrombocytopenia
Prognostic Factors:
• Based on RAI classification

• Lymphocytosis
• Lymphadenopathy
• Splenomegaly or Hepatomegaly
• Anemia
• Thrombocytopenia
Prognostic
Factor Survival
5 year survival is 10-35% for all patients
with AML
AML 5-10% will survive more than 5 years
20-35% for young patients who undergo

chemotherapy and BMT
Children 60-70% 5-year disease free survival

ALL
Adults 25-35% 5-year survival
CML Median survival 5-6 years
Stage O > 15 years
Stage I 9 years
CLL Stage II 5 years
Stage III and IV 2 years

Leukemia 2

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KEGANASAN HEMATOLOGI

• BLOOD SMEAR : MORPHOLOGI

• Short course of symptoms

• Fatigue, fever, easy bruising, bleeding

• More than 20% blasts in bone marrow

• Blasts in peripheral blood in 90% cases

• Toxic chemical exposure

• Medication (Alkylating-agents, Topoisomerase-II

• Most related to anemia, leukocytosis, leukopenia,

• Symptoms usually present for 3 months or more

• CBC with manual differential

• Anemia (normochromic, normocytic)

• Leukocytosis (median = 15,000)

• Thrombocytopenia (< 100,000)

• > 20% myeloblasts in blood and/or bone marrow

• Auer Rods (cytoplasmic granules)

• Positive myeloperoxidase reaction in > 3% blasts

• World Health Organization Classification

AML w/o maturation M0 no azurophil granules -

AML M1 few Aeur rods del(5); del(7); +8

dry' aspirate; biopsy

• Approximately 3,000 new cases per year

• Mostly affects children, accounts for 2/3 of

• Comprises less than 20% of leukemia in young

• May be B-cell, T-cell, or null-type (non-B, non-T

• Uncertain, but several proposed linkages:

·Viral infection (EBV, HIV)

·Exposure to high energy radiation (T-cell ALL)

·Toxic chemical exposure

• CBC with manual differential

• Anemia (normochromic, normocytic)

• WBC < 5,000 (or > 25,000)

• Leukocytosis (median = 15,000)

• Thrombocytopenia (< 50,000)

Pre-B cell ALL L1, L2 75 t(9:22) t(4:11) t(1:19)

T-cell ALL L1, L2 20 14q11 or 7q34

B-cell ALL L3 5 t(8:14) t(8:22) t(2:8)

L1 - 85% of childhood ALL

• Adult vs Childhood type

• Bone marrow biopsy is obtained

• If >5% of blasts with >20% cellularity, then

• Stem cell transplant may be necessary if

• Most are asymptomatic at presentation

• Strikingly elevated WBC

• Philadelphia chromosome (9:22) in up to 95%

• BCR-ABL protein junction

• CBC with manual differential

• Anemia (normochromic, normocytic)

• Leukocytosis (median = 20,000)

• Thrombocytopenia (< 100,000)

• Chronic phase: 3-5 years. Current treatment is with

• Accelerated phase: New nonrandom cytogenic

• Blast phase: > 30% blasts in blood or marrow. Treatment

• Uncertain, several proposed linkages:

• CBC with manual differential

• Increased number of lymphocytes on smear

• B-cells with CD 19 and CD 5 on flow cytometry

• Small lymphocitic lymphoma present in histology

0 Low Lymphocytosis alone