The document discusses leukemia, which is a group of cancers that affect the blood and bone marrow. There are four main types discussed: acute lymphocytic leukemia (ALL), acute myelogenous leukemia (AML), chronic lymphocytic leukemia (CLL), and chronic myelogenous leukemia (CML). ALL typically occurs in children and is treated with chemotherapy given in three phases: induction, consolidation, and maintenance. AML occurs more often in older adults and involves chemotherapy as well as sometimes stem cell transplantation. CLL and CML typically affect older populations and are generally managed with chemotherapy, immunotherapy, or targeted therapies depending on symptoms. Treatment for all forms aims to induce remission and prevent relapse using various protocols.

1. LEUKEMIA
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2. OVER VIEW
The stem cells are committed to
produce specific types of blood
cells. Lymphoid stem cells produce
either T or B lymphocytes.
Myeloid stem cells differentiate
into three broad cell types: RBCs,
WBCs, and platelets.
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4. Function of the bone marrow
The bone marrow is found in the inside of
bones. The marrow in the large bones of
adults produces blood cells. Approximately
4% of our total bodyweight consists of bone
marrow.
There are two types of bone marrow:
 1. Red marrow, made up mainly of myeloid
tissue.
 2. Yellow marrow, made up mostly of fat
cells.

5. Red marrow can be found in the flat
bones, such as the breast bone, skull,
vertebrae, shoulder blades, hip bone
and ribs. Red marrow can also be found
at the ends of long bones, such as the
humerus and femur.

6.  White blood cells (lymphocytes), red blood
cells and platelets are produced in the red
marrow. Red blood cells carry oxygen, white
blood cells fight diseases. Platelets are
essential for blood clotting.
 Yellow marrow can be found in the inside of
the middle section of long bones.

7.  White blood cells, which help to body fight
infection.
 Red blood cells, which carry oxygen to all
parts of the body.
 Platelets, which help in blood clot.
If a person loses a lot of blood the body can
convert yellow marrow to red marrow in
order to raise blood cell production.

8. Leukamia is a group of malignant
disorder, affecting the blood and
blood –forming tissue of the bone
marrow lymph system and spleen.
DEFINITION
The word Leukemia comes from the
Greek leukos which means "white"
and aima which means "blood".Medrockets.com

9. ETIOLOGY
 Heredity
 Infections: Human T cell leukaemia-lymphoma virus I
(HTLV-I)
 Environmental factors – Ionising radiation –
Chemical carcinogens – Certain drugs.
 Association with diseases of immunity:
Immunodeficiency diseases like AIDS and iatrogenic
immunosuppression induced by chemotherapy or
radiation,
 Congenital anomaly
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10.  The lack of control causes –
 nomal bone marrow to be replaced by
immature and undifferentiated leukocytes or
blat cells . –
 abnormal immature leukocytes then circulates
in the blood and infiltrate the blood forming
organs ( liver , spleen, lymph nodes) and other
sites throughout the body.
PATHOPHYSIOLOGY

11. LASSIFICATION OF LEUKAMIA
• French-American-British (FAB) CLASSIFICATION
– Based on morphology and cytochemistry,#
– It divides AML into 8 subtypes (M0 to M7)
• WHO CLASSIFICATION (2002)
– differs from revised FAB classification
– limited reliance on cytochemistry for making the diagnosis
of subtype of AML
– Based on clinical, cytogenetic and molecular abnormalitie

12. WHO CLASSIFICATION (2002)
 • AML with recurrent cytogenetic abnormalities
 • AML with multilineage dysplasia
 • AML and MDS (Myelodysplastic Syndrome),
therapy-related
 • AML, not otherwise categorised
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16. Classification of Lukemia

17. Usually occurs before 14 years of age peak
incidence is between 2-9 years of age, older adult
Pathophysiology
It arising from a single lymphoid stem cell, with
impaired maturation and accumulation of the
malignant cells in the bone marrow.
Acute lymphatic leukaemia (ALL)

18. Clinical features of ALL
 Anemia
 Bleeding
 Lymphaedopathy
 Infection
Fever
Pallor
Bleeding
Anorexia
Fatigue
Weakness
Bone, joint and
abdominal pain
Increase intracranial
press.
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19. Diagnosis
Low RBCs count, Hb, Hct, low platelet count , low
normal or high WBC count.
Blood smear show immature lymph blasts.
Treatment
Chemotherapeutic agent, it involve three phases
1. Induction: Using vincristine and prednisone.
2. Consolidation: Using modified course of
intensive therapy to eradicate any remaining.
3. Maintenance
ALL

20. Treatment Cont.
Prophylactic treatment of the CNS , intrathecal
administration and /or craniospinal radiation with eradicate
leukemic cells.
Eat diet that contains high in protein, fibres and fluids.
Avoid infection (hand washing, avoid crowds),injury
Take measure to decrease nausea and to promote appetite,
smoking and spicy and hot foods.
Maintain oral hygiene.
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21. Acute Myelogenous Leukamia (AML)
It occurs at any age but occurs most often at
adolescence and after age of 55
Characterized by the development of
immature myeloblasts in the bone marrow.
Clinical manifestations of AML are divided
into 2 groups due to
– Bone marrow failure
– Organ infiltration
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22. Clinical Features: Bone marrow failure
Anaemia producing pallor, lethargy, dyspnoea.
• Bleeding manifestations due to thrombocytopenia
causing spontaneous bruises, petechiae, bleeding from
gums and other bleeding tendencies.
• Infections are quite common and include those of mouth,
throat, skin, respiratory, perianal and other sites.
• Fever : no obvious source of infection can be found and
may occur in the absence of infection
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23. • due to replacement of the marrow and other tissues by
leukaemic cells.
• Pain and tenderness of bones (e.g. sternal tenderness) -
bone infarcts or subperiosteal infiltrates by leukaemic cells.
• Lymphadenopathy and enlargement of the tonsils may
occur
• Splenomegaly of moderate grade may occur – Splenic
infarction, subcapsular haemorrhages, and rarely, splenic
rupture may occur.
• Hepatomegaly
Clinical Features: Organ infiltration
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24. Laboratory Findings
The diagnosis of AML is made by a combination of routine blood
picture and bone marrow examination, coupled with cytochemical
stains and other special laboratory investigations.
• BLOOD PICTURE.
– Anaemia.
– Thrombocytopenia: moderately to severely reduced (below
50,000/μl) but occasionally it may be normal.
– White blood cells: ranges from subnormal-to-markedly elevated
values
• 25% of patients – reduced to 1,000-4,000 /μl.
• More often, however, there is progressive rise in white cell
count which may exceed 100,000/μl in more advanced disease.
• Majority of leucocytes in the peripheral blood are blasts and
there is often neutropenia due to marrow infiltration by leukaemic
cells.

25. BONE MARROW EXAMINATION
• Cellularity: Typically, the marrow is hypercellular but sometimes
a ‘blood tap’ or ‘dry tap’ occurs.
• Leukaemic cells
– generally tightly packed with leukaemic blast cells
– Romanowsky stains: cytochemical stains may be employed to
know the type of leukaemia.
Erythropoiesis.
• Erythropoietic cells are reduced.
• Megakaryocytes. They are usually reduced or absent.
• Cytogenetics: shows karyotypic abnormalities in 75% of cases
which may have a relationship to prognosis.
• Immunophenotyping. AML cells express CD13 and CD33
antigens. M7 shows CD41 and CD42 positivity.
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26. Treatment and Complications
• ANAEMIA AND HAEMORRHAGE.
– Anaemia and haemorrhage are managed by fresh blood transfusions and platelet
concentrates.
– Patients with severe thrombocytopenia (platelet count below 20,000/μl) require regular
platelet transfusions
• haemorrhage is an important cause of death in these cases
• CYTOTOXIC DRUG THERAPY
– Aim: firstly induce remission, secondly to continue therapy to reduce the hidden
leukaemic cell population by repeated courses of therapy.
– The most effective treatment of AML is a combination of 3 drugs: cytosine arabinoside,
anthracyclines (daunorubicin, adriamycin) and 6-thioguanine.
– Another addition is amsacrine (m-AMSA) administered with cytosine arabinoside, with
or without 6-thioguanine.
• BONE MARROW TRANSPLANTATION
– Bone marrow (or stem cell) transplantation from suitable allogenic or autologous donor –
The basic principle of marrow transplantation is to reconstitute the patient’s
haematopoietic system after total body irradiation and intensive chemotherapy
– kill the remaining leukemic cell
– Bone marrow transplantation has resulted in cure in about half the cases.

27. Prognosis
• Remission rate with AML is lower (50-70%)
than in ALL,
• Often takes longer to achieve remission, and
disease- free intervals are shorter.
• AML is most malignant of all leukaemia
• Survival with treatment is 12-18 months.
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28. Chronic lymphocytic Leukaemia
(CLL)
The incidence of CLl increases with age and is rare under
the age of 35.It is common in men.
It is characterized by proliferation of small, abnormal ,
mature B lymphocytes, often leading to decreased
synthesis of immunoglobulin and depressed antibody
response.
The number of mature lymphocytes in peripheral
blood smear and bone marrow are greatly increased
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29. Clinical Manifestation
Usually there is no symptoms.
Chronic fatigue , weakness , anorexia,
splenomegaly , lymphadenopathy, hepatomegaly.
Signs and Symptoms
Pruritic vesicular skin lesions .
Anaemia
Thrombocytopenia.
The WBC count is elevated to a level between
20,000 to 100,000.
Increase blood viscosity and clotting episode.
CLL
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30. I. Treatment is only when there are symptoms, particular anaemia ,
thrombocytopenia , enlarged lymph nodes and spleen appear.
I. Chemotherapy agents such as chlorambucil , and the
glucocorticoids.
Management
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31. Chronic Myelogenous Leukaemia(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
Occurs between 25-60 years of age. Peak 45 year
It is caused by benzene exposure and high doses of radiation.
It is associated with Philadelphia chromosome
Philadelphia chromosome is the chromosome abnormality
that causes chronic myeloid leukemia
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32. There is usually no symptoms.
The classic symptoms, include:
Fatigue, weakness, fever.
Weight loss, joint & bone pain.
Massive splenomegaly
 The accelerated phase of disease(blostic phase) is characterized
by increasing number of granulocytes in the peripheral blood.
There is a corresponding anaemia and thrombocytopenia.
Clinical Manifestation
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33. Laboratory Findings
• The diagnosis of CML is generally possible on blood picture alone. However, bone
marrow, cytochemical stains and other investigations are also useful
• BLOOD PICTURE – Anaemia. Anaemia is usually of moderate degree and is
normocytic normochromic in type.
– White blood cells. Characteristically, there is marked leucocytosis (approximately
200,000/μl or more at the time of presentation).
The natural history of CML consists of 3 phases—chronic, accelerated, and blastic.
• Chronic phase: begins as a myeloproliferative disorder and consists of excessive
proliferation of myeloid cells of intermediate grade (i.e. myelocytes and
metamyelocytes) and mature segmented neutrophils.
• Accelerated phase: increasing degree of anaemia, blast count in blood or marrow
between 10-20%, marrow basophils 20% or more, and platelet count falling below
1,00,000/μl.
• Blastic phase or blast crisis: blood or marrow blasts >20%.
Myeloid blast crisis in CML is more common and resembles AML.
– Auer rods are not seen in myeloblasts of CML in blast crisis.
– Platelets. Platelet count may be normal but is raised in about half the cases.

34. • Cellularity: hypercellularity with total or partial replacement of fat spaces by
proliferating myeloid cells.
• Myeloid cells: predominate in the bone marrow with increased myeloid-
erythroid ratio. The differential counts of myeloid cells in the marrow show
similar findings as seen in the peripheral blood with predominance of
myelocytes.
• Erythropoiesis: normoblastic but there is reduction in erythropoietic cells.
• Megakaryocytes: are conspicuous but lare usually smaller in size than normal.
• Cytogenetics: the characteristic chromosomal abnormality called Philadelphia
(Ph) chromosome (90-95%)
• CYTOCHEMISTRY
• The only significant finding on cytochemical stains is reduced scores of
neutrophil alkaline phosphatase (NAP)
• These helps to distinguish CML from myeloid leukaemoid reaction in which
case NAP scores are elevated
• OTHER INVESTIGATIONS
• Elevated serum vitamin B 12 and vitamin B12 binding capacity.
• Elevated serum uric acid (hyperuricaemia).
BONE MARROW EXAMINATION

35. Knowledge of molecular mechanism of CML has brought about major changes
in its therapy.
• The approach of modern therapy in CML is targetted at removal of all
malignant clones of cells bearing BCR/ABL fusion protein,
• So that patient reverts back to prolonged non-clonal haematopoiesis.
• This is achievable by the following approaches
– Imatinib oral therapy
– Allogenic bone marrow (stem cell) transplantation.
– Interferon-α.
– Chemotherapy
– Others: splenic irradiation, splenectomy and leucopheresis.
• The most common cause of death (in 80% cases) in CML is disease
acceleration and blastic transformation
The commonly drugs are hydroxyurea and busulfan
The only potential curative therapy of CML is the bone marrow transplant.
Treatment
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36.  The type of leukemia (acute or chronic)
 Age
 Whether leukemia cells were found in
cerebrospinal fluid
Treatment of Leukamia depends
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37. watchful waiting,
chemotherapy,
 targeted therapy,
 radiation therapy, and
stem cell transplant.
MANAGEMENT
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38. chemotherapy
 People with acute leukemia need to be
treated right away.
 The goal of treatment is to destroy signs of
leukemia in the body and make symptoms
go away. This is called a remission.
 After people go into remission, more
therapy may be given to prevent a relapse.
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39. The 3 phases of treatment protocols are
 Induction phase; the usual criteria for complete remission
are 5% of the bone marrow cells and normal peripheral
blood counts. Once remission completes the consolidation
phase begins.
 Consolidation phase; modified course of intensive
chemotherapy are given to eradicate any remaining disease.
Usually a higher dose of one or more chemotherapeutic
agents are administered.
 Maintenance phase; small dose of different combination of
chemotherapeutic agents are given every 3 to 4 weeks. This
phase may continue for a year or longer and is structured to
allow the client to live as normal life as possible

40. Targeted therapy
 This affects only tumor cells and spare normal cells. hence
decreasing the associated toxicities. Gemtuzumab
ozofamicin (mylotarg) is an anti D33nmonoclonal antibody
linked to calicheamicin, which is potent cytotoxic agent.
STEM CELL TRANSPLANT
Goal;
 Totally eliminate leukemic cells from the body using combinations of
chemotherapy with or without total body irradiation
 Eradicates patient’s hematopoietic stem cells
 Replaced with those of an HLA-matched (Human Leukocyte Antigen)
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41. THANK YOU
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