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CHAPTER 10:
ACUTE LEUKEMIA
NORASIDI RAFFIE
UNIVERSITI SELANGOR
OBJECTIVE
1. To study the concept of leukemia
2. To know the types of acute and chronic leukemia
2
LEUKEMIA
Definition:
Leukemia is a cancer of blood
forming cells, characterized by
the accumulation of malignant
white blood cells in the bone
marrow, bloodstream and the
lymphatic systems.
3
How does leukemia affect blood cells?
1. When leukemia occurs, normal control mechanisms
break down and the bone marrow starts to produce
large numbers of abnormal leukemic cells.
2. The cell type affected is almost the white blood cells
(WBC).
4
How does leukemia affect blood cells?
(cont’d)
3. These abnormal leukemia cells begin to multiply
uncontrollably to take over the bone marrow and
spill into the bloodstream and the lymph system.
They may even infiltrate vital organs.
4. The bone marrow is no longer able to maintain its
production of the normal cell type, and this causes
the whole balance of blood to be disturbed.
5
Actual causes: unknown, but it has been reported to be triggered
by:
1. Radiation - exposure to radiation or carcinogenic substances
(cigarette)
2. Chemicals & drugs - expose to petrochemical such as benzene,
petrol, coloring hair dye.
3. Viruses - HIV, HTLV-1
4. Genetics inherited / chromosomal disorder / somatic mutation
in the DNA - which activates oncogenes or inactivate tumor
suppressor genes, e.g., syndrome down; trisomy 21
6
Causes / etiology factors
1. Based on cells type
• Myeloid - when leukemia affects the myeloid cells.
(monocyte and granulocyte series)
• Lymphoid - when leukemia affects the lymphoid cells
(lymphocyte series)
7
General Classification
2. Based on stage of cells differentiation
• Acute - more immature cells, occurs in all age;
typically, in children between 2 – 7-year-old and
young adult (15 years old), WBC is variable.
• Chronic - more mature cells, occurs in adults, WBC is
increased
8
General Classification
1. Acute leukemia
• acute myeloid leukemia (AML)
• acute chronic leukemia (ALL)
2. Chronic leukemia
• chronic myeloid leukemia (CML)
• chronic lymphoid leukemia (CLL)
9
Types of leukemia
Acute
leukemia
• Definition:
Defined as the presence
of over 30% of
malignant blast cells in
the bone marrow at
clinical presentation.
• It is further subdivided
into 2 groups based on
whether the blast are
shown to be myeloblast
or lymphoblast
10
11
Morphological studies
- FAB classification
WHO classification
Immunological
markers
Cytogenetics /
molecular studies
Cytochemistry studies
Acute leukemia
Classifications of acute leukemia is determined based on:
Acute myeloid
leukemia – FAB
classification (8
subtypes)
Acute lymphoid
leukemia – FAB
classification (3
subtypes)
13
L1 - Small uniform / homogenous blast cells with scanty cytoplasm
L2 - larger blast cell with prominent nucleoli and cytoplasm and the blast
are more heterogeneity
L3 - larger blast cell with prominent nucleoli, strongly basophilic with
cytoplasmic vacuoles
Acute myeloid leukemia (WHO classification)
14
Acute lymphoid leukemia (WHO classification)
15
According to the recommendation of the;
• European Group for the Immunological classification of
Leukemias (EGIL)
• British Committee for Standards in Hematology
16
Acute leukemia – Immunological
markers classification
Acute Myeloid
Leukaemia
(AML)
Acute Lymphoid Leukaemia
(ALL)
Markers B T
Myeloid
CD13 positive negative Negative
CD33 Positive negative Negative
Glycophorin Positive (M6) negative Negative
Platelet antigens
e.g CD41
Positive (M7) negative Negative
Myeloperoxidase Positive (M0) negative Negative
Lymphoid
i) B-lineage
CD19 Negative positive Negative
CD22 Negative positive Negative
CD10 Negative positive Negative
cIg negative positive Negative
ii) T-lineage
CD7 Negative Negative positive
cCD3 Negative Negative Positive
Acute Myeloid
Leukaemia (AML)
Acute Lymphoid
Leukaemia (ALL)
t (8;21) Positive (M2) None
t (15;17) Positive (M3) None
t (4;11) none Positive (T-ALL)
t (12;21) none Positive (T-ALL)
t (1;19) none Positive (B-ALL)
18
Acute leukemia – Cytogenetics / molecular
studies classification
Acute Myeloid
Leukaemia
(AML)
Acute Lymphoid
Leukaemia
(ALL)
Myeloperoxidase positive negative
Sudan Black B positive negative
Periodic Acid Schiff negative positive
Acid Phosphatase negative positive
19
Acute leukemia – Cytochemistry study
Acute leukemia – Cytochemistry study
• AML-myeloperoxidase AML-SBB
20
Signs and Symptoms
These symptoms can develop over weeks or months:
1. Loss of energy and pallor from anemia (lack of red
cells).
2. Persistent or recurrent infections such as sore throats,
ear infections.
3. Nose bleeds and excessive bruising.
4. Blood spots on the skin from lack of platelets.
21
Lab Investigations
1. Normochromic normocytic anaemia
2. Thrombocytopenia
3. Total WBC count may be decreased, normal or
increased up to 200x109/L
4. Blood film show variable number of blast cells
5. The BM is hypercellular with > 30% of leukemic
blasts cells (lymphoblast).
22
Treatments
1. Blood product support with RBC and platelet transfusion.
2. Treatment of infections (antibiotic, antimicrobial drugs)
3. Chemotherapy using cytotoxic drugs (at least three drugs
given) to induce remission (Remission - absence of any clinical
or conventional laboratory evidence of the disease)
4. Allopurinol - (to prevent tumor lysis syndrome such as
hyperuricemia) due to cytotoxic drugs
5. Radiotherapy
6. Stem cell transplant
23
References
1. Hoffbrand, A.V. and Petit, J.E., & Moss P.A.H. Essential Haematology, 5th
Edition, Blackwell Science Publications, 2003
2. Dacie and Lewis Practical Haematology. Lewis SM, Bain BJ, Bates I. Ninth
Edition. Churchill Livingstone, 2002.
24

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ACUTE LEUKAEMIA.pptx

  • 1. CHAPTER 10: ACUTE LEUKEMIA NORASIDI RAFFIE UNIVERSITI SELANGOR
  • 2. OBJECTIVE 1. To study the concept of leukemia 2. To know the types of acute and chronic leukemia 2
  • 3. LEUKEMIA Definition: Leukemia is a cancer of blood forming cells, characterized by the accumulation of malignant white blood cells in the bone marrow, bloodstream and the lymphatic systems. 3
  • 4. How does leukemia affect blood cells? 1. When leukemia occurs, normal control mechanisms break down and the bone marrow starts to produce large numbers of abnormal leukemic cells. 2. The cell type affected is almost the white blood cells (WBC). 4
  • 5. How does leukemia affect blood cells? (cont’d) 3. These abnormal leukemia cells begin to multiply uncontrollably to take over the bone marrow and spill into the bloodstream and the lymph system. They may even infiltrate vital organs. 4. The bone marrow is no longer able to maintain its production of the normal cell type, and this causes the whole balance of blood to be disturbed. 5
  • 6. Actual causes: unknown, but it has been reported to be triggered by: 1. Radiation - exposure to radiation or carcinogenic substances (cigarette) 2. Chemicals & drugs - expose to petrochemical such as benzene, petrol, coloring hair dye. 3. Viruses - HIV, HTLV-1 4. Genetics inherited / chromosomal disorder / somatic mutation in the DNA - which activates oncogenes or inactivate tumor suppressor genes, e.g., syndrome down; trisomy 21 6 Causes / etiology factors
  • 7. 1. Based on cells type • Myeloid - when leukemia affects the myeloid cells. (monocyte and granulocyte series) • Lymphoid - when leukemia affects the lymphoid cells (lymphocyte series) 7 General Classification
  • 8. 2. Based on stage of cells differentiation • Acute - more immature cells, occurs in all age; typically, in children between 2 – 7-year-old and young adult (15 years old), WBC is variable. • Chronic - more mature cells, occurs in adults, WBC is increased 8 General Classification
  • 9. 1. Acute leukemia • acute myeloid leukemia (AML) • acute chronic leukemia (ALL) 2. Chronic leukemia • chronic myeloid leukemia (CML) • chronic lymphoid leukemia (CLL) 9 Types of leukemia
  • 10. Acute leukemia • Definition: Defined as the presence of over 30% of malignant blast cells in the bone marrow at clinical presentation. • It is further subdivided into 2 groups based on whether the blast are shown to be myeloblast or lymphoblast 10
  • 11. 11 Morphological studies - FAB classification WHO classification Immunological markers Cytogenetics / molecular studies Cytochemistry studies Acute leukemia Classifications of acute leukemia is determined based on:
  • 12. Acute myeloid leukemia – FAB classification (8 subtypes)
  • 13. Acute lymphoid leukemia – FAB classification (3 subtypes) 13 L1 - Small uniform / homogenous blast cells with scanty cytoplasm L2 - larger blast cell with prominent nucleoli and cytoplasm and the blast are more heterogeneity L3 - larger blast cell with prominent nucleoli, strongly basophilic with cytoplasmic vacuoles
  • 14. Acute myeloid leukemia (WHO classification) 14
  • 15. Acute lymphoid leukemia (WHO classification) 15
  • 16. According to the recommendation of the; • European Group for the Immunological classification of Leukemias (EGIL) • British Committee for Standards in Hematology 16 Acute leukemia – Immunological markers classification
  • 17. Acute Myeloid Leukaemia (AML) Acute Lymphoid Leukaemia (ALL) Markers B T Myeloid CD13 positive negative Negative CD33 Positive negative Negative Glycophorin Positive (M6) negative Negative Platelet antigens e.g CD41 Positive (M7) negative Negative Myeloperoxidase Positive (M0) negative Negative Lymphoid i) B-lineage CD19 Negative positive Negative CD22 Negative positive Negative CD10 Negative positive Negative cIg negative positive Negative ii) T-lineage CD7 Negative Negative positive cCD3 Negative Negative Positive
  • 18. Acute Myeloid Leukaemia (AML) Acute Lymphoid Leukaemia (ALL) t (8;21) Positive (M2) None t (15;17) Positive (M3) None t (4;11) none Positive (T-ALL) t (12;21) none Positive (T-ALL) t (1;19) none Positive (B-ALL) 18 Acute leukemia – Cytogenetics / molecular studies classification
  • 19. Acute Myeloid Leukaemia (AML) Acute Lymphoid Leukaemia (ALL) Myeloperoxidase positive negative Sudan Black B positive negative Periodic Acid Schiff negative positive Acid Phosphatase negative positive 19 Acute leukemia – Cytochemistry study
  • 20. Acute leukemia – Cytochemistry study • AML-myeloperoxidase AML-SBB 20
  • 21. Signs and Symptoms These symptoms can develop over weeks or months: 1. Loss of energy and pallor from anemia (lack of red cells). 2. Persistent or recurrent infections such as sore throats, ear infections. 3. Nose bleeds and excessive bruising. 4. Blood spots on the skin from lack of platelets. 21
  • 22. Lab Investigations 1. Normochromic normocytic anaemia 2. Thrombocytopenia 3. Total WBC count may be decreased, normal or increased up to 200x109/L 4. Blood film show variable number of blast cells 5. The BM is hypercellular with > 30% of leukemic blasts cells (lymphoblast). 22
  • 23. Treatments 1. Blood product support with RBC and platelet transfusion. 2. Treatment of infections (antibiotic, antimicrobial drugs) 3. Chemotherapy using cytotoxic drugs (at least three drugs given) to induce remission (Remission - absence of any clinical or conventional laboratory evidence of the disease) 4. Allopurinol - (to prevent tumor lysis syndrome such as hyperuricemia) due to cytotoxic drugs 5. Radiotherapy 6. Stem cell transplant 23
  • 24. References 1. Hoffbrand, A.V. and Petit, J.E., & Moss P.A.H. Essential Haematology, 5th Edition, Blackwell Science Publications, 2003 2. Dacie and Lewis Practical Haematology. Lewis SM, Bain BJ, Bates I. Ninth Edition. Churchill Livingstone, 2002. 24