1
Leukemia
Abdirahman Jibril
2
Leukemia
 A group of malignant disorders affecting
the blood and blood-forming tissues of
– Bone marrow
– Lymph system
– Spleen
 Occurs in all age groups
3
Leukemia
 Results in an accumulation of
dysfunctional cells because of a loss of
regulation in cell division
 Fatal if untreated
– Progressive
4
Leukemia
 Often thought of as a childhood disease
 The number of adults affected with
leukemia is 10 times that of children
5
Leukemia
Etiology and Pathophysiology
 No single causative agent
 Most from a combination of factors
– Genetic and environmental influences
6
Leukemia
Etiology and Pathophysiology
 Associated with the development of
leukemia
– Chemical agents
– Chemotherapeutic agents
– Viruses
– Radiation
– Immunologic deficiencies
lecture leukemia.ppt
8
Classification of leukemias
Two major types (4 subtypes) of leukemias
Acute leukemias
Acute lymphoblastic leukemia (ALL)
Acute myelogenous leukemia (AML)
(also "myeloid" or "nonlymphocytic")
Chronic leukemias
Chronic lymphocytic leukemia (CLL)
Chronic myeloid leukemia (CML)
(Within these main categories, there are typically several
subcategories)
10
Leukemia
Classification
 Acute versus chronic
– Cell maturity
• Acute: clonal proliferation of immature
hematopoietic cells (the formation of
blood or blood cells )
• Chronic: mature forms of WBC; onset is
more gradual
– Nature of disease onset
11
Myelogenous Leukemia
 Leukemia characterized by proliferation
of myeloid tissue (as of the bone marrow
and spleen) and an abnormal increase in
the number of granulocytes, myelocytes,
and myeloblasts in the circulating blood
 Myeloid tissue is a biologic tissue with the
ability to perform hematopoiesis. It is mainly
found as the red bone marrow in bones, and is
often synonymous with this. However, myeloid
can also be present in the liver and spleen .
 A myelocyte is a young cell of the granulocytic
series, occurring normally in bone marrow, but
not in circulating blood (except when caused by
certain diseases).
12
 Granulocytes are a category of white
blood cells characterized by the presence
of granules in their cytoplasm.[1] They are
also called polymorphonuclear leukocytes
(PMN or PML) because of the varying
shapes of the nucleus, which is usually
lobed into three segments.
 The myeloblast is a unipotent stem cell,
which will differentiate into one of the
actors of the granular series.
8/12/2009 13
14
Acute Myelogenous Leukemia
(AML)
 Leukemia characterized by proliferation of myeloid
tissue (as of the bone marrow and spleen) and an
abnormal increase in the number of granulocytes,
myelocytes, and myeloblasts in the circulating blood
 One fourth of all leukemias
– 85% of the acute leukemias in adults
 Abrupt, dramatic onset
– Serious infections, abnormal bleeding
 Uncontrolled proliferation of myeloblasts
– Hyperplasia of bone marrow and spleen
15
Acute Lymphocytic Leukemia
(ALL)
 Most common type of leukemia in
children
 15% of acute leukemia in adults
 Immature lymphocytes proliferate in the
bone marrow
16
Acute Lymphocytic Leukemia
 Signs and symptoms may appear
abruptly
– Fever, bleeding
 Insidious with progressive
– Weakness, fatigue
 Central nervous system manifestations
17
Chronic Myelogenous Leukemia
(CML)
 Excessive development of mature
neoplastic granulocytes in the bone
marrow
– Move into the peripheral blood in
massive numbers
– Ultimately infiltrate the liver and
spleen
18
Chronic Myelogenous Leukemia
 Philadelphia chromosome
– The chromosome abnormality that
causes chronic myeloid leukemia
(CML) (9 &22)
– Genetic marker
 Chronic, stable phase followed by acute,
aggressive (blastic) phase
19
Chronic Lymphocytic Leukemia
(CLL)
 Production and accumulation of
functionally inactive but long-lived,
mature-appearing lymphocytes
 B cell involvement
 Lymph node enlargement is noticeable
throughout the body
– ↑ incidence of infection
20
Chronic Lymphocytic Leukemia
 Complications from early-stage CLL is
rare
– May develop as the disease advances
– Pain, paralysis from enlarged lymph
nodes causing pressure
21
Hairy Cell Leukemia
 2% of all adult leukemias
 Usually in males > 40 years old
 Chronic disease of lymphoproliferation
– B lymphocytes that infiltrate the bone
marrow and liver
22
Hairy Cell Leukemia
 Cells have a “hairy” appearance
 Symptoms from
– Splenomegaly, infection, vasculitis
 Treatment
– alpha-interferon, pentostatin,
cladribine
23
Unclassified Leukemias
 Subtype cannot be identified
 Malignant leukemic cells may have
– Lymphoid, myeloid, or mixed
characteristics
 Frequently these patients do not respond
well to treatment
– Poor prognosis
Differential Diagnosis
1. Aplastic anemia
2. Myelodysplastic syndromes
3. Multiple myeloma
4. Lymphomas
5. Severe megaloblastic anemia
6. Leukemoid reaction
25
Leukemia
Clinical Manifestations
 Relate to problems caused by
– Bone marrow failure
• Overcrowding by abnormal cells
• Inadequate production of normal marrow
elements
• Anemia, thrombocytopenia, ↓ number
and function of WBCs
26
Leukemia
Clinical Manifestations
 Relate to problems caused by
– Leukemic cells infiltrate patient’s
organs
• Splenomegaly
• Hepatomegaly
• Lymphadenopathy
• Bone pain, meningeal irritation, oral
lesions (chloromas)
27
Leukemia
Diagnostic Studies
 To diagnose and classify
– Peripheral blood evaluation (CBC and
blood smear)
– Bone marrow evaluation
 To identify cell subtype and stage
– Morphologic, histochemical,
immunologic, and cytogenic methods
28
Leukemia
Collaborative Care
 Goal is to attain remission (when there is
no longer evidence of cancer cells in the
body)
 Chemotherapeutic treatment
– Induction therapy
• Attempt to induce or bring remission
• Seeks to destroy leukemic cells in the
tissues, peripheral blood, bone marrow
• Patient may become critically ill
– Provide psychological support as well
29
What is remission?
The main aim of treatment for acute lymphoblastic
leukaemia is to give a remission. This means that the
abnormal, immature white cells or blasts can no longer
be detected in the blood or bone marrow, and normal
bone marrow has developed again.
 For many people with acute lymphoblastic leukaemia
the remission lasts indefinitely and the person is said to
be cured.
30
Leukemia
Collaborative Care
 Chemotherapeutic treatment (cont.)
– Intensification therapy
• High-dose therapy
• May be given after induction therapy
• Same drugs at higher doses and/or other
drugs
31
Leukemia
Collaborative Care
 Chemotherapeutic treatment (cont.)
– Consolidation therapy
• Started after remission is achieved
• Purpose is to eliminate remaining
leukemic cells that may not be evident
– Maintenance therapy
• Lower doses of the same drug
32
Leukemia
Chemotherapy Regimens
 Combination chemotherapy
– Mainstay treatment
– 3 purposes
• ↓ drug resistance
• ↓ drug toxicity to the patient by using
multiple drugs with varying toxicities
• Interrupt cell growth at multiple points in
the cell cycle
33
Leukemia - Bone Marrow and Stem
Cell Transplantation
 Goal
– Totally eliminate leukemic cells from
the body using combinations of
chemotherapy with or without total
body irradiation
34
Leukemia - Bone Marrow and Stem
Cell Transplantation
 Eradicates patient’s hematopoietic stem cells
 Replaced with those of an HLA-matched
(Human Leukocyte Antigen)
• Sibling (is a brother or a sister; that is, any
person who shares at least one of the same
parents )
• Volunteer
• Identical twin
• Patient’s own stem cells removed before
Treatment
 Goals
 1- Remission induction (chemo for 28 days)
 2-Response assessment ( D 28)
 3-Consolidation (chemo / SCT)
 4- Maintinence.
35
36
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lecture leukemia.ppt

  • 2. 2 Leukemia  A group of malignant disorders affecting the blood and blood-forming tissues of – Bone marrow – Lymph system – Spleen  Occurs in all age groups
  • 3. 3 Leukemia  Results in an accumulation of dysfunctional cells because of a loss of regulation in cell division  Fatal if untreated – Progressive
  • 4. 4 Leukemia  Often thought of as a childhood disease  The number of adults affected with leukemia is 10 times that of children
  • 5. 5 Leukemia Etiology and Pathophysiology  No single causative agent  Most from a combination of factors – Genetic and environmental influences
  • 6. 6 Leukemia Etiology and Pathophysiology  Associated with the development of leukemia – Chemical agents – Chemotherapeutic agents – Viruses – Radiation – Immunologic deficiencies
  • 8. 8
  • 9. Classification of leukemias Two major types (4 subtypes) of leukemias Acute leukemias Acute lymphoblastic leukemia (ALL) Acute myelogenous leukemia (AML) (also "myeloid" or "nonlymphocytic") Chronic leukemias Chronic lymphocytic leukemia (CLL) Chronic myeloid leukemia (CML) (Within these main categories, there are typically several subcategories)
  • 10. 10 Leukemia Classification  Acute versus chronic – Cell maturity • Acute: clonal proliferation of immature hematopoietic cells (the formation of blood or blood cells ) • Chronic: mature forms of WBC; onset is more gradual – Nature of disease onset
  • 11. 11 Myelogenous Leukemia  Leukemia characterized by proliferation of myeloid tissue (as of the bone marrow and spleen) and an abnormal increase in the number of granulocytes, myelocytes, and myeloblasts in the circulating blood
  • 12.  Myeloid tissue is a biologic tissue with the ability to perform hematopoiesis. It is mainly found as the red bone marrow in bones, and is often synonymous with this. However, myeloid can also be present in the liver and spleen .  A myelocyte is a young cell of the granulocytic series, occurring normally in bone marrow, but not in circulating blood (except when caused by certain diseases). 12
  • 13.  Granulocytes are a category of white blood cells characterized by the presence of granules in their cytoplasm.[1] They are also called polymorphonuclear leukocytes (PMN or PML) because of the varying shapes of the nucleus, which is usually lobed into three segments.  The myeloblast is a unipotent stem cell, which will differentiate into one of the actors of the granular series. 8/12/2009 13
  • 14. 14 Acute Myelogenous Leukemia (AML)  Leukemia characterized by proliferation of myeloid tissue (as of the bone marrow and spleen) and an abnormal increase in the number of granulocytes, myelocytes, and myeloblasts in the circulating blood  One fourth of all leukemias – 85% of the acute leukemias in adults  Abrupt, dramatic onset – Serious infections, abnormal bleeding  Uncontrolled proliferation of myeloblasts – Hyperplasia of bone marrow and spleen
  • 15. 15 Acute Lymphocytic Leukemia (ALL)  Most common type of leukemia in children  15% of acute leukemia in adults  Immature lymphocytes proliferate in the bone marrow
  • 16. 16 Acute Lymphocytic Leukemia  Signs and symptoms may appear abruptly – Fever, bleeding  Insidious with progressive – Weakness, fatigue  Central nervous system manifestations
  • 17. 17 Chronic Myelogenous Leukemia (CML)  Excessive development of mature neoplastic granulocytes in the bone marrow – Move into the peripheral blood in massive numbers – Ultimately infiltrate the liver and spleen
  • 18. 18 Chronic Myelogenous Leukemia  Philadelphia chromosome – The chromosome abnormality that causes chronic myeloid leukemia (CML) (9 &22) – Genetic marker  Chronic, stable phase followed by acute, aggressive (blastic) phase
  • 19. 19 Chronic Lymphocytic Leukemia (CLL)  Production and accumulation of functionally inactive but long-lived, mature-appearing lymphocytes  B cell involvement  Lymph node enlargement is noticeable throughout the body – ↑ incidence of infection
  • 20. 20 Chronic Lymphocytic Leukemia  Complications from early-stage CLL is rare – May develop as the disease advances – Pain, paralysis from enlarged lymph nodes causing pressure
  • 21. 21 Hairy Cell Leukemia  2% of all adult leukemias  Usually in males > 40 years old  Chronic disease of lymphoproliferation – B lymphocytes that infiltrate the bone marrow and liver
  • 22. 22 Hairy Cell Leukemia  Cells have a “hairy” appearance  Symptoms from – Splenomegaly, infection, vasculitis  Treatment – alpha-interferon, pentostatin, cladribine
  • 23. 23 Unclassified Leukemias  Subtype cannot be identified  Malignant leukemic cells may have – Lymphoid, myeloid, or mixed characteristics  Frequently these patients do not respond well to treatment – Poor prognosis
  • 24. Differential Diagnosis 1. Aplastic anemia 2. Myelodysplastic syndromes 3. Multiple myeloma 4. Lymphomas 5. Severe megaloblastic anemia 6. Leukemoid reaction
  • 25. 25 Leukemia Clinical Manifestations  Relate to problems caused by – Bone marrow failure • Overcrowding by abnormal cells • Inadequate production of normal marrow elements • Anemia, thrombocytopenia, ↓ number and function of WBCs
  • 26. 26 Leukemia Clinical Manifestations  Relate to problems caused by – Leukemic cells infiltrate patient’s organs • Splenomegaly • Hepatomegaly • Lymphadenopathy • Bone pain, meningeal irritation, oral lesions (chloromas)
  • 27. 27 Leukemia Diagnostic Studies  To diagnose and classify – Peripheral blood evaluation (CBC and blood smear) – Bone marrow evaluation  To identify cell subtype and stage – Morphologic, histochemical, immunologic, and cytogenic methods
  • 28. 28 Leukemia Collaborative Care  Goal is to attain remission (when there is no longer evidence of cancer cells in the body)  Chemotherapeutic treatment – Induction therapy • Attempt to induce or bring remission • Seeks to destroy leukemic cells in the tissues, peripheral blood, bone marrow • Patient may become critically ill – Provide psychological support as well
  • 29. 29 What is remission? The main aim of treatment for acute lymphoblastic leukaemia is to give a remission. This means that the abnormal, immature white cells or blasts can no longer be detected in the blood or bone marrow, and normal bone marrow has developed again.  For many people with acute lymphoblastic leukaemia the remission lasts indefinitely and the person is said to be cured.
  • 30. 30 Leukemia Collaborative Care  Chemotherapeutic treatment (cont.) – Intensification therapy • High-dose therapy • May be given after induction therapy • Same drugs at higher doses and/or other drugs
  • 31. 31 Leukemia Collaborative Care  Chemotherapeutic treatment (cont.) – Consolidation therapy • Started after remission is achieved • Purpose is to eliminate remaining leukemic cells that may not be evident – Maintenance therapy • Lower doses of the same drug
  • 32. 32 Leukemia Chemotherapy Regimens  Combination chemotherapy – Mainstay treatment – 3 purposes • ↓ drug resistance • ↓ drug toxicity to the patient by using multiple drugs with varying toxicities • Interrupt cell growth at multiple points in the cell cycle
  • 33. 33 Leukemia - Bone Marrow and Stem Cell Transplantation  Goal – Totally eliminate leukemic cells from the body using combinations of chemotherapy with or without total body irradiation
  • 34. 34 Leukemia - Bone Marrow and Stem Cell Transplantation  Eradicates patient’s hematopoietic stem cells  Replaced with those of an HLA-matched (Human Leukocyte Antigen) • Sibling (is a brother or a sister; that is, any person who shares at least one of the same parents ) • Volunteer • Identical twin • Patient’s own stem cells removed before
  • 35. Treatment  Goals  1- Remission induction (chemo for 28 days)  2-Response assessment ( D 28)  3-Consolidation (chemo / SCT)  4- Maintinence. 35