2. LUKEMIAS
Leukemia is a type of cancer of blood or
bone marrow
Characterized by an abnormal of
increased immature white blood cell
called blasts
luka means white , emia means blood
3. Definition
A group of malignant diseases in
which genetic abnormalities in a
hematopoietic cell give rise to
unregulate clonal proliferation of
cells.
4. Cont..
Leukemia is the most common type of
childhood malignancy characterised by
persistent and uncontrolled production of
immature and abnormal white blood cells. It is
a disease of abnormal proliferation and
maturation of bone marrow which interferes
the production of normal RBCS and WBCs
and Platelets.
5. History of luekemia
1845- Craig and Bennet described as case
as suppuration of the blood
1855-Ernest Neumann discovered that the
bone marrow was the likely origin of
Leukemia
6. 1946- Sidney farber used antifolate to treat
leukemia in children
1960’s Addition of vincristine and steroids
used in regimen- survival rates increased
over 50%
7.
8. `also called leucocyte count
Mobile units of the body’s protective system
Formed partially in bone marrow (granulocytes
and monocytes and few lymphocytes) and
partially in lymph tissue( lymphocytes and
plasma cells)
After formation, they are transported in the
blood to different parts of the body where they
are needed
9. General characteristics of leucocytes
Types of WBC
Six types of WBC are normally present in blood
Polymorphonuclear neutrophils
Polymorphonuclear eosinophils
Polymorphonuclear basophils
Monocyte
Lymphocyte
Occasionally plasma cells
12. Genesis of WBC
Two major lineages of WBCs are formed, the
myelocytic and the lymphocytic lineages, beginning
with the myeloblast; the lymphocytic linege , beginning
with the lymphoblast
WBC formed in the bone marrow and stored within the
marrow untill they are needed in the circulatory system
13. When need arises, various factors cause them to
release
Lymphocytes stored in lymphoid tissue
Megakaryocytes formed in bone marrow, the small
fragments known as platelets( or thrombocytes),
then pass in to the blood
14.
15.
16.
17.
18. Incidence
Most common malignant neoplasm in
children
31% of all malignancies occur in children
ALL-11%
CML-2-3%
Juvenile myelomonocytic Leukemia-1-2%
19. Males are commonly than females
Whites more than blacks
More commonly in Downs syndrome
20. Different types of leukemia
It may be acute or chronic
Acute leukemia gets worse very fast and may
make feel sick right away
Chronic leukemia gets worse slowly and may
not cause symptoms for years
22. Classification
Cell type Acute Chronic
Lymphocytic or
Lymphoblastic
leukemia
Acute
lymphoblastic
leukemia (ALL)
Chronic
lymphoblastic
leukemia (CLL)
Myelogenous
leukemia or also
called myeloid or
non lymphocytic
Acute
Myelogenous
leukemia (AML)
Chronic
Myelogenous
leukemia (CML)
30. Pathophysiology
Neoplastic proliferation of immature of WBC
in blood forming tissues of the body
Pathology and clinical manifestation due
infiltration and replacement of any body
tissues with non functional leukemic cells
Immature WBC circulate in the blood
31. Immature WBC do not directly attack or
destroy normal blood cells
Destruction of normal blood cells occurs
due to competition for nutrients
33. Uncontrolled proliferation of leucocyte
precursors
Competition for nutrients, infiltration of organs and
replacement of normal cells with leukemic cells
Bone marrow dysfunction reticulous endothelium
generalised hyper metabolism CNS
35. Effect of leukemia in body
Metastatic growth of leukemic cells in
abnormal areas of the body
Leukemic cells from the bone marrow
may reproduce and invade
surrounding bones pain
Bone fracture
36. Leukaemia spreads to spleen,liver and
other vascular regions
Development of infection
Severe anemia
Bleeding tendency caused by
thrombocytopenia
These effects results mainly from the
normal bone marrow an lymphoid cells by
the non function of leukemic cells
37. Acute lymphocytic leukemia
ALL is a primary disorder of bone marrow in
which the bone marrow elements are
replaced by immature or undifferentiated
blast cells. It is characterized by anaemia,
thrombocytopenia and neutropenia
39. EPIDEMOLOGY
ALL is diagnosed as 300 children and
adolescence < 20yr in united states each
year
2-3 yr of age
It occurs in boys than in girls at all ages
The disease more common in children with
any chromasomal abnormalities
Identical twins- risk to develop second twin
40. ETIOLOGY
Exact etiology is unknown
Genetic abnormalities
Environmental factors
Post conception somatic mutations in
lymphoid cells
Association between B cell ALL
Epstein Barr virus infection
42. WHO Classification
B lymphoblastic leukemia
(85%precusor B-ALL or pre-B ALL)
T- lymphoblastic leukemia
Mature B cell ALL or Burkitt
Leukemia ( rare)
43.
44.
45.
46. acute lymphoblastic leukemia is caused by a series of acquired
genetic aberrations.
Malignant transformation usually occurs at the pluripotent stem cell
level, although it sometimes involves a committed stem cell with
more limited capacity for self-renewal.
Abnormal proliferation, clonal expansion, aberrant differentiation,
and diminished apoptosis (programmed cell death) lead to
replacement of normal blood elements with malignant cells.
Pathophysiology
49. Joint swelling
Bone or joint pain
Pallor
Exercise intolerance ,bruising
Oral mucosal bleeding or epistaxis
fever
Disease
progress
50. Due to organ infiltration
Lymphadenopathy
Hepatospleenomegaly
Testicular enlargement
Central nervous system
involvement(cranial neuropathies,
headache,seizures)
54. CBC ( anemia, thrombocytopenia)
Many patient with ALL present with total leucocyte
count of <10,000 U/L
Bone marrow examination- leukemic marrow is
hyper cellular with 60-100% immature WBC and
normal marrow components.
Bone marrow aspirate
(morphology,immunophenotype,cytogenetics and
FISH)
55. Reduced marrow elements and replacement by lymphoblast. Neoplastic
lymphoblast are slightly larger than lymphocytes and have scant, faintly
basophilic cytoplasm and round or convoluted nuclei with inconspicuous
nucleoli and fine chromatin often in a smudged appearance
56. CSF examination- increased CSF leucocyte count
(younger than 1 yr- 0-30 mm3
age 1-4 years- 0-20mm3
age 5 yrs to puberty-0-10mm3)
Radiological studies- presence of mediastinal mass
Coagulation profile
Lumbar puncture
57. LFT , RFT, elecrolytes
hyperuricemia, hyperphosphatemia, hyperkalemia,
hypocalcemia, and elevated lactate dehydrogenase
(LDH), which indicate a tumor lysis syndrome.
Elevated serum hepatic transaminases or creatinine,
and hypoglycemia may also be present
62. Consolidation( intesification)phase
Focus on intensive CNS therapy in
combination with continued intensive
systemic therapy – to prevent CNS relapses
Intrathecal chemotherapy- LP
Prophylactic treatment of CNS with cranial
irradiation or intrathecal administration of
methotrexate
63. corticosteroid such as dexamethasone/predinsolone
Danomycin at weekly interval
CNS disease- radiation therapy
73. On laboratory findings
Hb- low( anemia)
Platelet count –low (thrombocytopenia)
Bone marrow examination- leukemic cells are
hyper cellular with 60-100% immature WBC
and normal marrow components.
LFT and RFT
74. Peripheral blood smear- bone marrow
failure
CSF examination- elevate leucocyte
count(younger than 1 yr- 0-30 mm3
age 1-4 years- 0-20mm3
age 5 yrs to puberty-0-10mm3)
75. Acute pain related to infiltration of
leukemic cells, hepatospleenomegaly
Nursing order
Administer analgesics ( acetaminophen ) as per
order
Check vital signs
Place in position of comfort and support joints and
extremitties with pillows or padings
Provide diversional activities(play therapy)
76. Ineffective tissue perfusion
related to anemia
Nursing orders
Blood transfusion with PRBC (raisedto Hb
level above 10gm/dl)
Administer oxygen
Recheck blood investigation( Hb,Hct,
Peripheral smear)
77. Risk for infection related to abnormal
bone marrow function
Antibiotic therapy as per order
Adequate protein and calorie rich ,low fat
foods included in diet( egg, milk,fish, poultry,
and lean meats, whole grains, vegetables etc)
Avoid live vaccine (measles, mumps,
rubella, varicella) to leukemic children
Universal precautions
To send blood, urine stool culture
78. Risk for haemorrhage related to abnormal
bone marrow function
Nursing order
Administer platelet concentrates as per
order
Use soft toothbrush toys without sharp
edges
Shot cut nails
provide soft foods
Children are kept away from activities that
might cause injury
79. Imbalance nutrition less than body
requirements related to anorexia,nausea,
vomiting and gingival ulcer
Nursing order
Mild to moderate vomiting- antiemetics
( promethazine, chlorpromazine)
Severe- metoclopramide
Antiemetics given before30 mts-1 hr of
chemotherapy
81. Disturb body image related to alopecia
as side effects of chemotherapy
Hair should be cut short and wear surgical cap
Purchase wig for child before hairfall occurs
Reassured that hair will grow again after the
treatment stops
82. Activity intolerance related to
anemia or pain
Calm and quiet environment
Rest and sleep
Assist in ADL
Promote hygenic care
Correct anemia
Relieve pain by administer
analgesics(morphine)
83. Parentral anxiety related to disease and
treatment regimen
Emotional support
Encourage to express their feelings
Given community resources and social support
84. Knowledge deficit related to continuation
of long term care and side effects of
chemotherapy
Health maintenance
Regular blood test
Chemotherapy management
Management of side effects of chemotherapy
85. It includes
Nausea and vomiting
Anorexia
Mucosal ulceration
Neuropathy
Haemorrhagic cystitis
Alopecia
Mood changes
86. Prognosis
Hypodiploidy
Philadelphia chromosome positivity
T cell ALL
MLL rearrangement
IKZF1 gene deletion
age< 1 yr
Age>10yr
Leucocyte count>50000/cu mm
Presence of CNS disease
poor
87. Favourable prognostic factors are
Age 3 to 9 years
WBC count < 25,000/mcL (< 25 × 109/L) or
< 50,000/mcL (< 50 × 109/L) in children
Leukemic cell karyotype with high hyperdiploidy (51 to
65 chromosomes), t(1;19), and t(12;21)
No CNS disease at diagnosis
88. Acute Myeloid Leukemia
It also known as
o Acute myelocytic leukemia
o Acute myelogeneous leukemia
o Acute non lymphocytic leukemia
89. Stem cell disorder characterized by clonal
expansion of myeloid precursor cells with
reduced capacity to differentiate. That is
MATURATION ARREST
90. epidemiology
AML accounts for 11% of the cases of
childhood leukemia in United states
Diagnosed in approximately 370 children
annually
94. pathophysiology
Genetic mutation in FLT3,oncogenic Ras,BCR/ABL
Mutation and translocation fusion products that
impair differentiation and apoptosis
95. Includes PML/RAR∞ fusion from t(15:17), AML-
1/ETO fusion from t(8:12) and MLL rearrangements
Presence of both type of genetic changes in the
hematopoeitic precursor cells leads to AML
102. Headache, vision changes, non focal
neurologic abnormalities
DIC
Discrete masses known as chloromas or
granulocytic sarcomas
Chloromas also may be seen in the orbit and
epidural space
103. Diagnosis
Bone marrow aspiration
Flow cytometry and special stains
Some chromosomal abnormalities and molecular
genetic markers are the characteristics of specific
subtype of disease
WBC – can be normal, low or high
RBC features- severe anemia
Platelet count low
104. Treatment
Chemotherapy
Cytosine- arabinoside continous IV infusion for 7
days
IV daunorubicin for 3 days
Over 70% of the cases show remission with these
drugs
Intrathecal CNS prophylaxis may be indicated in
case of CNS involvement
105. Stem transplantation is recommended only
after a relapse
Arsenic tromide is an effective noncytotoxic
therapy for APL( acute promyelocytic
leukemia)
106. Supportive care
Blood and platelet transfusion
Iv antibiotic therapy
Cranial irradiation and bone marrow
transplantation
107. Chronic Myelocytic Leukemia
CML is characterised by increased number of
myeloid cells in all stages of maturation both in
blood and bone marrow
CML is a clonal disorders of the hematopoietic
tissue that accounts for 2-3% of all cases of
childhood leukemia
108. Approximately 99% of the cases are characterised by
specific translocation (t(9;22), q 34; q11)known as the
philadelphia chromasome, resulting in a BCR-ABL
fusion protein.
CML accounts for 15% of all cases leukemia
109. The annual incidence of CML s 1.5 cases per
100,000 individuals.
Male female ratio – 1.6:1
No familial association in CML exposure to
ionizing radiation has increased risk of CML
110. Clinical features
Presenting symptoms of CML are non specific
Fever
Fatigue
Weight loss
Anorexia
Spleenomegaly
Other features includes arthritis, priapism,
retinopathy, skin infiltration and unexplained fever
111. Diagnostic features
Blood examination- anaemia, thrombocytosis
and excess leucocyte count
Bone marrow examination shows hyperplasia
Cytogenetic and molecular studies- presence
of Philadelphia chromosome
112.
113. Treatment
Adult type CML is done with hydroxyurea or
bursurfan to keep the WBC count below
100,000/cmm
Spleenic radiation, interferon and bone
marrow transplantation are also indicated for
treatment of CML
117. Acute leukemia in early childhood
Acute leukemia in early childhood is biologically and clinically distinct. The particular
characteristics of this malignancy diagnosed during the first months of life have
provided remarkable insights into the etiology of the disease. The pro-B, CD10 negative
immunophenotype is typically found in infant acute leukemia, and the most common
genetic alterations are the rearrangements of the MLL gene. In addition,
the TEL/AML1 fusion gene is most frequently found in children older than 24 months. A
molecular study on a Brazilian cohort (age range 0-23 months) has
detected TEL/AML1+ve (N = 9), E2A/PBX1+ve (N = 4), PML/RARA+ve (N = 4),
and AML1/ETO+ve (N = 2) cases. Undoubtedly, the great majority of genetic events
occurring in these patients arise prenatally. The environmental exposure to damaging
agents that give rise to genetic changes prenatally may be accurately determined in
infants since the window of exposure is limited and known. Several studies have shown
maternal exposures that may give rise to leukemogenic changes.
119. Siblings (brothers and sisters) of children with
leukemia have a slightly increased chance of
developing leukemia, but the overall risk is
still low. The risk is much higher among
identical twins. If one twin develops childhood
leukemia, the other twin has about a 1 in 5
chance of getting leukemia as well.
120. Lifestyle-related risk factors for some adult
cancers include smoking, being overweight,
drinking too much alcohol, and getting too
much sun exposure. These types of factors
are important in many adult cancers, but they
are unlikely to play a role in most childhood
cancers.
121. Other factors that have been studied for a possible link to
childhood leukemia include:
Exposure to electromagnetic fields (such as living near
power lines)
Living near a nuclear power plant
Infections (especially from viruses) early in life
Mother’s age when child is born
Parent’s smoking history
Fetal exposure to hormones such as diethylstilbestrol (DES)
or birth control pills
Father’s workplace exposure to chemicals and solvents
Chemical contamination of ground water
122. Food Consumption by Children and
the Risk of Childhood Acute Leukemia
The authors’ objective was to determine what
particular foods consumed early in life (first 2
years) are associated with risk of childhood
leukemia
These results suggest that fruits or fruit juices that
contain vitamin C and/or potassium may reduce
the risk of childhood leukemia, especially if they
are consumed on a regular basis during the first 2
years of life.
