Anemia in Children

Noorhaswati Izura 42788

Noorul Fatimah 42791
Normazwin 42933
Esther Symbah 45548
Fatin Nabila 45570

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 Definition

• Anemia is defined as reduced haemoglobin level

below the normal range
• Anemia according to age
- Neonate : Hb < 14 g/dl
- 1-12 m.o: Hb < 10 g/dl
- 1-12 y.o: Hb <11 g/dl
• Generally cause by ↓ / impaired RBC
production, ↑ destruction or blood loss

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Types of anemia based on MCV value/size of RBC

Microcytic Normocytic Macrocytic

• Thalessemia • Chronic • Folate
• Iron disease deficiency
deficiency • Chronic • B12
anemia inflammation deficiency
• Lead • Malignancy • Congenital
poisoning • Acute aplasticc
• Sideroblastic bleeding anemia
anemia • Hypersplenis • Trisomy 21
• Copper m antibody • Hypothyroidis
deficiency mediated m
• Hb E and C hemolysis 3
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 History taking and P.E
• Age, sex, race
• Diet, medication, chronic disease, infection, travel hx
• Family hx of anemia
• Clinical features (only apparent when Hb <7-8 g/dl)
i. Pallor
ii. Sleepiness
iii. Feeding slowly
iv. Irritability
v. Reduced exercise tolerance
vi. Weakness
vii. Tachypnea
viii. Tachycardia
ix. Cardiac flow murmur
x. Cardiac dilatation
xi. Associated sx based on associated disorders

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 Iron deficiency anemia

• Most common type of anemia

• Causes of IDA:
1. Inadequate intake
*Additional iron is needed for ↑ blood volume, growth and to build up
iron stores, iron requirement is about 1mg/kg/day in children

Source of iron in children:

Breast milk: 1.5 g/L, 50% absorbed
Infant formula: 5-9 g/L, 10% absorbed
Cow’s milk: 0.5 g/L, 10% absorbed
Mixed diet: 4-9 g/L, 10-15% absorbed

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• Inadequate intake may be cause by
➢ Delay in introducing mixed feeding beyond 6 m.o
➢ Insufficient iron-rich foods
➢ Consumption of large amount of cow’s milk (child
became full quickly and refuse to eat)

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2. Malabsorption
➢ Due to parasitic infestation in the intestine
➢ Consumption of tea (contain tannin)

3. Chronic blood loss

➢ Bleeding from lesion in GIT (peptic ulcer, Meckel
diverticulum, polyp, hemagioma, IBD)

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 Clinical feature
• Lethargy
• Feeding more slowly
• Pallor – conjunctivae, palm
• Irritability
• Anorexia
• Systolic flow murmur
• Tachycardia
• High output cardiac failure may occur
• Sx of iron deficiency:
- Pica (desire to ingest non-food materials; soil, chalk, foam
rubber)
- Pagophabia: desire to ingest ice

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 Investigation
Test Expected result
Full blood count ➢Low haemoglobin level than normal
value
➢Low MCV (microcytic)
➢Low MCH (hypochromic)
➢Normal WBC, platelet
Peripheral blood smear Microcytic hypochromic RBC
Reticulocyte count Normal
Serum iron ↓
Serum ferritin (iron-storage) ↓
Total iron binding capacity ↑
Stool culture for occult blood/parasite To exclude blood loss/malabsorption
as the cause of IDA

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 Differential diagnosis

• Thalassemia
• Hemoglobin C and E disease
• Anemia of chronic disease ( rare to cause microcytic
anemia)
• Lead poisoning
• Rare microcytic anemia (sideroblastic anemia)

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 Treatment
Nutritional counseling
• Maintain breastfeeding.
• Use iron fortified cereals.

Oral iron medication

• Give 6 mg/kg/day of elemental iron in 3 divided doses,
continue for 6-8 weeks after haemoglobin level is restored
to normal.
• Syrup FAC (Ferrous ammonium citrate): the content of
elemental iron per ml
depends on the preparation available.
• Ferrous fumarate 200 mg has 66 mg of elemental iron
per tablet.
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Consider the following if failure to response to oral iron:
• Non-compliance.
• Inadequate iron dosage.
• Unrecognized blood loss.
• Impaired GI absorption.
• Incorrect diagnosis.

Blood transfusion
• No transfusion required in chronic anaemia unless signs of
decompensation
(e.g. cardiac dysfunction) and the patient is otherwise debilitated.
• In severe anaemia (Hb < 4 g/dL) give low volume packed red
cells (< 5mls/kg).
• If necessary over 4-6 hours with IV Frusemide (1mg/kg) midway.

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 Epidemiology
• Most often occur in people from the
– Indian subcontinent, Mediterranean, Middle East, Greek Cypriots

• In Malaysia, the carrier rate estimation,

– β-thalassaemia: 3-5%.
– α-thalassaemia 1.8-7.5%
– Haemoglobin E (HbE): 5-46%

• β-thalassaemia carrier interacts with a HbE carrier may result in the

birth of a patient with HbE/β-thalassaemia or thalassaemia
intermedia with variable clinical severity;
– Mild forms (asymptomatic),
– Moderate to severe (behave like β-thalassaemia major patients)
Hb types in newborns and adults

Newborn HbF (74%), HbA (25%), HbA2

(1%)
Children >1 year old and HbA(97%), HbA2 (2%)
adult
β Thalassemia: What is it?
Inherited haemoglobin production disorder:
Point mutations in β–globin genes on chromosome
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β chain
HbA (97%), HbA2 (2%)
x
α2β2 α2δ2
production

absence (β0) reduced (β+)

Various combination:
(eg β+/β+ , β0/β0 Or β+/
β0)
 Types of β Thalassemia
β Thalassemia minor/ β Thalassemia β Thalassemia
trait/ carrier intermedia major
β-globin β/β+ (heterozygous) β+/β+ or co- βo/βo
inheritance of β No β globin chain
thalassemia trait with No HbA
another
heamoglobinopathy (eg,
sickle-cell β+
thalassemia)
Symptoms None or mild, well Moderate anemia
tolerated anemia
which may be worsen
by pregnancy
Misdiagnosed as iron-
def anemia??
Clinical signs Low MCV & MCH ± splenomegaly
HbA2 >3.5%
Slight increase in HbF
(1-3%)
Need of - -
β Thalassemia major/ Cooley’s Anemia

- Clinical features
Presented at 4-6 months
of age
▪ Pale skin
Severe anemia ▪ Fatigue
(no β , excess α globin:
▪ Weakness
unstable - hemolysis)
▪ Protruding abdomen
Jaundice
Blood transfusion dependent from 3-6
months of age
▪ Failure to thrive/
growth failure
▪ Extramedullary
haemopoiesis Must be regular to prevent
▪ Hepatosplenomegaly
▪ Bone marrow
expansion
β Thalassemia major/ Cooley’s Anemia

- Clinical features

Classical facies
▪ Skull bossing
▪ Maxillary overgrowth
“Hair on end” appearance in X-ray due to increase marrow activity
(L- normal, R– thalassemia)

Peripheral blood film:

▪ Hypochromic (Low MCH)
▪ Microcytic cell (Low MCV)
▪ Target cells
▪ Nucleated RBCs
Prenatal diagnosis:

DNA analysis by chorionic villus sampling at 9-11 weeks
period of gestation
 α thalassemia
• Normal = 4 α globin genes
• Manifestation depends on the number of functional α
globin genes that have been deleted
• Deletions of the alpha-globin gene is most frequently
encountered in Southeast Asian origin populations.
Types
 α thalassemia major 

(Hb Barts hydrop fetalis)
• Deletion of all 4 α globin genes ! fetal
anemia (present in mid-trimester)
• Usual effect? Any possible survivor??
• Dx: USG, Hb electrophoresis or Hb high
performance liquid chromatography
(HPLC)
The only long term survivors of Hb Barts
are those who received monthly
intrauterine transfusion followed by
lifelong monthly transfusion after birth
Cont.. α thalassemia major 

(Hb Barts hydrop fetalis)

➢ Odema and ascites (severe

abdominal swelling) from fetal
anemia
➢ Swollen liver
 PBF of α thalassemia

• Howell-Jolly bodies
– A type of inclusion containing DNA, removed by splenic macrophage
– Can be seen when RBC fails to mature or functional spleen is absent
 Investigation for diagnosis

1. FBC (Hb typically <7mmol/dL)

2. Peripheral blood film
3. Haemoglobin electrophoresis (for Hb analysis): HbF
↑↑, HbA <97% or absent, HbA2 variable/ high
4. Serum ferritin (To rule out iron deficiency anemia vs β
thalassemia trait)
5. DNA analysis (ideal)
 Management

1. Blood transfusion complications iron chelation

therapy
2. Bone marrow transplantation
3. Splenectomy
4. Patients and parents support groups
 Complications of chronic iron overload
in Thalassaemics over 10 years (CEH)

• Cardiac: arrhythmias, pericarditis, cardiac failure.

• Endocrine: growth retardation, impaired glucose

tolerance, pubertal delay, hypothyroidism,
hypoparathyroidism and diabetes mellitus.

• Hepatic: liver cirrhosis

 Investigation for management
• Before first transfusion
– Red cell phenotyping (ideal)
– Infection screen: HIV, Hep B&C, VDRL screen (before
first transfusion)
• After few transfusion:
– Liver function test, etc
• Bone marrow transplantation:
– HLA typing (for all patient with unaffected siblings)
 Management:

Iron chelation therapy
• Goal: To prevent iron overload in
transfusion dependent thalassemia
• Iron chelators:
– Subcutaneous: Desferrioxamine (Desferal®)
• When to start? Complications?
– Orally: Deferiprone, Deferasirox
 Management: Bone marrow
transplantation
• To consider this option, patient should be classified into
Pesaro risk groups based on the presence of 3 risk factors
– Hepatosplenomegaly >2cm
– Presence of liver cirrhosis
– Irregular iron chelation
▪ Best results if performed at the earliest age as possible in Class 1
patient
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 Haemolytic anemia

• Increased red cell destruction

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• • Reduced red cells lifespan due to increased red cell
destruction in the circulation (intravascular hemolysis) or
liver or spleen (extravascular hemolysis)

• • Normal red cells lifespan : 120 days

• • In haemolysisà red cell survival maybe reduced to few

days but bone marrow production can increase about 8-
fold.

• • Hemolysis only lead to anaemia when the bone marrow

is no longer able to compensate for the premature
destruction of red cells.

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 Haemoglobinopathies
• Inherited Hb abnormalities

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• - Reduced / absent production of HbA (α &-

β- thalassaemias)
• - Production of abnormal Hb (e.g sickle cell
disease)

Haemolytic anemia

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 Thalassemia
• β-thalasssemia & α-thalassemia

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 Sickel Cell Disease
• Autosomal recessive

• Irregular shaped cell stuck in blood vessels, slow or block blood flow and O2 to bosy.

• Exacerbated by low oxygen tension, cold, dehydration

• Main clinical features are:

• Anaemia
• Sickle cell crisis- pain at peripheral d/t vaso-occlusive at the tissue (swollen,irritate nerve
ending)

• Infection (affect spleen fx as filter bacteria & virus in blood)

• Splenomegaly
• Growth failure
• Liver disease (kupffer cell erythrophagocytosis and engorgement of sinusoids by aggregates sickle
cell)

• Jaundice & Gallstones (Chronic hemolysis-high bilirubin turnover-high pigment gallstone

formation)

• Priapism (persistent and painful erection of penis in teenage boys) 42

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Complication
Management
• prophylactic penicillin and
immunisation(since 2month- 5y.o.);
folic acid; maintain good hydration

Treat crises
• analgesia, hydration, antibiotics,
exchange or blood transfusion as
indicated

Long term
• hydroxyurea(reduce need of blood
transfusion and painful crisis by
stimulate production of fetal Hb) or bone
marrow transplant
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46
 Hereditary Spherocytosis & Hereditary
Elliptocytosis

• Autosomal dominant with spontaneous mutation Ø

• Lifespan 10-30 days
• Splenomegaly in 75% of patients
• Both conditons have a defect in red cell membrane protein (spectrin, ankyrin,
band 3) ( +protein4.1, glycophorin C) that underlies the RBC lipid bilayer.
• Function: Provide stability of the membrane shape.

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Clinical features Complication

• Anemia • Haemolytic crisis

• Jaundice • Aplastic megaloblastic crisis

(parvovirus infection)
• Splenomegaly
• Erythroblastopenic crisis
• Haemolytic crisis

• Megaloblastic crisis Dramatic fall in hemoglobin level

and reticulocyte count
• Aplastic crisis with parvovirus19
infection

• Pigmented gallstones in
adolescents

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 Investigations
1) Osmotic fragility test 2) Flow cytometric (dye-binding) test
• measure of the resistance of erythrocytes
to hemolysis by osmotic stress. • Deficiency or abnormality of Band 3
• Median Corpuscular Fragility may result in decreased fluorescence.
(MCF) is the concentration of sodium This is seen in HS red cells and has
chloride solution causing 50% lysis. also been observed in cases of South-
Normal MCF range is 4.0-4.45 g/L. east Asian elliptocytosis.

3) Peripheral blood film

• elliptocytes,
spherocytes,
fragmented RBCs,
and striking
microcytosis

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 Management
• Oral folic acid
•ØMild chronic haemolytic anaemia d/t raised folic acid demand
secondary to increased RBC production.

• Splenectomy

•ØNormalizes RBC survival in hereditary spherocytosis, but the

morphologic abnormalities persist.
•ØShould be deferred until age 5 year to minimize the risk of
overwhelming postsplenectomy sepsis and to maximize the antibody
response to the polyvalent pneumococcal vaccine.
• Blood transfusions

• Cholecystectomy

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 G6PD

• X-linked recessive inheritance

• abnormality in the pentose monophosphate shunt pathway of glycolysis that

results in the depletion of reduced NADPH and the inability to regenerate
reduced glutathione.

• NADPH maintain glutathione in reduced form(acts as scavenger for dangerous

oxidative metabolites).Pentose monophosphate pathway is the only source for
NADPH in RBC. Failed in pentose monophosphate pathway of glucose
metabolism make more vulnerable to oxidative stress and lead to hemolytic.

• When exposed to oxidant stress, haemoglobin will oxidize and form Heinz
body

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Pathophysiology

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 Acquired haemolytic anemia

Immune Non-immune

• Isoimmune hemolytic • Mechanical damage to RBC

anemia/ Transfusion 
 • Alteration in the plasma lipid
reaction
• Toxin
• Autoimmune hemolytic
anemia • Vitamin E deficiency

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• Isoimmune

• • Caused by active maternal immunization against

fetal antigens that the mother’s erythrocyte do not express

• • Examples : ABO and Rh incompatibility

• • Presentation varies based on severity. There may

be no clinical manifestations, or the infant may exhibit
jaundice, severe anemia and hydrop fetalis

• • Positive Coombs test in infant RBC confirm

diagnosis

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• Autoimmune Hemolytic Anemia

•Causes:
• - Post infection : Mycoplasma, EBV, or others
• - Chronic autoimmune disease : SLE,
lymphoproliferative disorder or immunodeficiency 

- Drug : Penicillin, Quinidine, alpha-methyldopa

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• Mechanical damage

• • In thrombotic microangiopathy, RBCs are trapped by fibrin strands in the

circulation and physically broken down shear stress as they pass through these strands

• • Causes :
• - Hemolytic Uraemic Syndrome
• - Disseminated Intravascular Coagulopathy
• - Thrombotic Throbocytopenic Purpura
• - Malignant Hypertension
• - Hyperacute renal graft rejection
• • Other example of mechanical injury:
• - Exposure to nonendothelialized surface e.g artifical heart valves
• - Giant hemangiomas/ Kasabach Merritt syndrome

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• Alteration in the Plasma lipids

• • Especially cholesterol
• • Lead to damage to RBC membrane and shorten RBC survival
• • Lipids in the plasma are in equilibrium with lipids in the
RBC membrane

• • High cholesterol levels increase the membrane cholesterol

and the total membrane surface without affecting the volume
of the cell
• • This condition produces spur cells that may be seen in
abetalipoproteinemia and liver diseases

• • Hemolysis occurs in the spleen, where poor RBC

deformability results in erythrocyte destruction
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• Toxins

• • Circulating toxin e.g snake venoms and heavy

metals that bind sulfhydryl groups may damage
the RBC membrane and induce hemolysis

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• Vitamin E deficiency

• • As a result of abnormal sensitivity of membrane

lipids to oxidant stress
• • May occur in premature infants who are not being
supplemented with vitamin E or who have
insufficient nutrition, in infants with severe
malabsorption syndrome e.g cystic fibrosis, and in
infants with transfusional iron overload, which can
lead to severe oxidant stress

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• Treatment and Prognosis

• • Management including administration of

corticosteroid and intravenous immunoglobulin
• • In drug induced hemolysis, removal of drugs
usually leads to resolution of hemolytic process
• • More than 80% of children with autoimmune
hemolytic anemia recover spontaneously

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Bone marrow failure
Aplastic anemia
Leukemia
Lymphoma

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 Aplastic anemia

Most common cause:

1) Congenital hypoplastic anemia (Diamond-Blackfan
Anemia)
• Rare condition, 90% recognized at 1st year of life
• Etiology: gene mutation causing defect of erythroid
progenitor cell resulting in ↑ apoptosis. 40% of cases are
dominant in inheritance.
• clinical feature:
- Pallor in the neonatal period, more prominent at 2-6 m.o
- Growth retardation (short stature)
- Congenital malformations
* Most common: craniofacial abnormalities; snub nose &
hypertelorism
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• Laboratory finding:
1. Macrocytic RBC (but no hypersegmented neutrophils)
2. Elevated HbF
3. Elevated erythrocyte adenosine deaminase activity
(distinguish feature from transient erythroblastopenia
of childhood)
4. Decrease reticulocyte count
5. Decrease RBC precursor in bone marrow (other
precursors are normal)

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Treatment
• Corticosteroids therapy, initially 2mg/kg/24 hour
• If does not respond to corticosteroid therapy: undergo
transfusion at 4-8 weeks interval

Differential diagnosis
• TEC
• Parvovirus infection
• Other macrocytic BM failure: Fanconi anemia,
Swachman-Diamond syndrome

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Fanconi anemia
• Inherited in autosomal recessive manner
• Etilogy: mutant gene proteins cause genomic instability,
chromosomal instability and fanconi anemia (due to
increase marrow cell cell apoptosis)
• CF: hyperpigmentation in trunk, neck, intertriginous
area
café-au-lait spot, short stature, growth failure,
underdeveloped sex organs, microcephaly, small eyes,
upper limb deformities
• Lab findings: thrombocytopenia, granulopenia,
macrocytic anemia, hypocellular and fatty marrow,
chromosome fragility

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2) Transient erythroblastopenia of childhood
• More common than DBA
• Severe, transient hypoplastic anemia in previously
healthy children btween 6 m.o – 3 y.o.
• Etiology: IgG, IgM, cell-mediated immune mechanism.
Familial cases also had been reported
• Laboratory finding: ↓ reticulocyte, normal MCV
(normocytic), normal HbF level, normal RBC ADA level
• All children recover within 1-2 months

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3) Parvovirus B19 infection
• Common infectious agent which cause erythema
infectiosum
• Common cause of RBC aplasia in immunodeficient and
chronic hemolysis patient and fetus in utero
• Etiology: virus is infective and cytotoxic to bone marrow
progenitor cells, specifically to P antigen on RBC
• Lab finding: nuclear inclusion in erythroblasts, giant
pronormoblasts from BMA specimen
• Usually recover in < 2 weeks except in immunodeficient
child

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 Lymphoma 



-defined as cancer of the lymph system (or lymphatic system), which is part of our immunity. It is
characterized by the formation of solid tumors in the immune system. The cancer affects immune
cells called lymphocytes, which are white blood cells.

• 3rd most common malignancy in childhood

• 2 major types Hodgkin disease and Non
Hodgkin Lymphoma
• Etiology unknown but many cases
suggests there is involvement of Epstein
Barr virus
 Clinical manifestation
• Painless, firm lymphadenopathy
(supraclavicular and cervical nodes)
• Mediastinal lymphadenopathy(producing cough
or shortness of breath)
• Fever more than 38 degree
• Drenching night sweats
• Unintentional weight loss
• Lack of energy
• Itchiness
 Non Hodgkins Lymphoma
• Malignancies of the cell in immune system
• Clinical features represent the pattern of migration of normal
lymphoid cells
• T cell malignancies represent like ALL or NHL(mediastinal mass with
varying degrees of bone marrow infiltration)
• B cell malignancies present as NHL and localised lymph node
disease usually in neck head or abdomen
• Abdominal diseases present with pain, a palpable mass or even
intussusception
 Hodgkin’s disease
• Uncommon in prepubertal children
• Presents as painless lymphadenopathy(neck)
• Lymph nodes are much larger and firmer.
• Systemic symptoms(sweating, pruritus, weight loss and
fever)
 Lab studies
• Blood count
• ESR
• Chest x ray
• Measurement of serum
electrolytes,calcium, phosphorus, lactate
dehydrogenase,uric acid
• Bone marrow aspiration(staging)
Ann Arbor Staging
 Treatment
• Combination of chemotherapy and low
dose, involved field radiation therapy
 Complication
• Immunosuppression
• Nausea and vomiting
• Alopecia
• Second malignant neoplasm
• Hypothyroidism
• Impaired soft tissue
• Bone growth
• Cardiac dysfunction
Leukaemia
 Definition
➢Is a malignant disorder of hematopoietic
stem cells characteristically associated
with increase number of white cells in
bone marrow or/and peripheral blood
 Epidemiology
• Acute lymphoblastic leukemia peaks
among 2-5 years old children
• Acute myeloid leukaemia has the lowest
incidence in young adult life and there is
striking rise over the age of 50
• Chronic lymphoblastic leukaemia and
chronic myeloid leukaemia mainly in
middle and old age.
 Classifications of Leukaemias

Cell type Acute Chronic

Lymphocytic Acute Chronic

Leukemia Lymphoblastic Lymphoblastic
Leukemia Leukemia

Myelogenous Acute Myelogenous Chronic

Leukemia Leukemia Myelogenous
Leukemia
Haemopoesis 

Classifications Acute Acute Chronic Chronic
Lymphoblastic Myelogenous Lymphoblastic Myelogenous
leukaemia Leukemia leukaemia leukaemia
Features

Age Group Predominantly in Older adults; Most common Adults between

children and median age is 50 leukemia in 25-60 years. Peaks
young adults years. adults. in the fourth and
Children : Peak fifth decades of
age 2-5 years old. life.

Pathogenesis 1.Due to Mutations in genes 1. Tumour cells Presence of BCR-

mutations of BCR- encoding contain high levels ABL fusion gene
ABL fusion gene trancription of BCL2, protein (9;22)
created by a factors. Mutation that inhibit translocation. The
(9;22) interfere with apoptosis. growth factor
chromosome myeloid cells 2. Immune dependence of
translocation. differentiations. dysregulation. CML progenitors
Thus, allow B (15;17) Patients have decrease by
cells proliferation translocations, autoantibodies signals generated
2. In T-ALLs, induce the against Rbcs and by BCL-ABL that
NUP214-ABL neoplastic platelets-thus, mimic the effect
fusion gene promyelocytes impair immune of growth factor
differentiate into tolerance. receptor
 Features of Acute Leukemias
➢ Abrupt, stormy onset. Most patients present for medical
attention within 3 months of the onset of symptoms.
➢ Clinical signs and symptoms related to suppressed marrow
function, including :-
▪ fatigue (due to anaemia)
▪ fever (reflecting infections due to neutropenia)
▪ bleeding (petechiae, ecchymoses, epistaxis, gum bleeding)
secondary to thrombocytopenia.
▪ Bone pain and tenderness due to marrow expansion and
infiltration of the subperiosteum
▪ Generalized lymphodenopathy, splenomegaly, and
hepatomegaly, due to dissemenation of the leukemic cells
▪ Central nervous system manifestations, including headache,
vomiting, and nerve palsies resulting from meningeal spread
Acute Lymphoblastic Leukaemia
Presentations :
• Signs and symptoms which reflect bone marrow infiltration
causing anaemia, neutropenia, thrombocytopenia and extra-
medullary disease.
• Pallor and easy bleeding – common
• Non remitting fever.
• Lymphadenopathy.
• Hepatosplenomegaly.
• Bone pains - not to be misdiagnosed as Juvenile Idiopathic
Arthritis (JIA).
• Uncommon at presentation: CNS involvement e.g. headache,
nausea and vomiting, lethargy, irritability, seizures or spinal
mass causing signs and symptoms of spinal cord compression.
• Testicular involvement, usually as a unilateral painless testicular
enlargement.
• Skin manifestations e.g. skin nodules.
 Investigations
• Full Blood Count (FBC) and Peripheral Blood Film
(PBF) - Anaemia and thrombocytopenia.
-Total White Count (TWC) can be normal, low or high.
-Occasionally PBF may not show presence of blast
cells.
• Bone marrow aspirate (BMA) and trephine biopsy.
• Bone marrow for flowcytometry analysis
(immunophenotyping).
• Bone marrow cytogenetics.
• Bone marrow/Blood for molecular studies wherever
possible.
 Investigations
• Cerebral Spinal Fluid (CSF) examination
for blast cells.
• CXR to evaluate for mediastinal masses.
 Differential Diagnosis
• For Acute leukaemia can be non-malignant and
malignant
• Non-malignant can be infections like EBV, CMV
• Non infectious can be aplastic anemia, ITP, juvenile
rheumatic arthritis-neutropenia,anaemia
• Malignant can be neuroblastoma, rhabdomyosarcoma,
Ewing sarcoma
• Fanconi Anaemia – decreased production of all types
blood cell
• Transient myoproleferative disorder-Leukocytosis,
anaemia, thrombocytopenia
• Non Hodgkin Lymphoma
 

Treatment 


➢ The regimes or treatment protocols used vary

according to originator groups/ institutions from
the various countries (BFM – Germany, MRC – UK,
CCG/COG – USA) but generally consists of
induction, central nervous system treatment/
prophylaxis, consolidation/intensification and
maintenance therapy.
 Guidelines of Treatment
• Check height, weight and calculate surface area (m2) every 3
months and adjust drug dosages accordingly.
• Check full blood count every 2 weeks for the first 1- 2 months after
starting maintenance chemotherapy and monthly thereafter if
stable.
• Bone marrow aspiration should be considered if counts are
repeatedly low or if there is clinical suspicion of relapse. Majority
of relapse (>2/3) would occur within the first year of stopping
treatment.
• CNS disease would present itself usually with headache, vomiting,
abnormal sensorium or hypothalamic symptoms (e.g. Hyperphagia
and abnormal weight gain).
• Testicular relapse present as a painless unilateral swelling.
• Cotrimoxazole is routinely used as prophylaxis against Pneumocystis
carinii pneumonia (PCP) and continued until the end of therapy. In
the event of chronic cough or unexplained tachypnoea, CXR is
required.
 Maintenance of Chemotherapy
• Check the TWC and Absolute Neutrophil Count
(ANC) threshold levels of the various
protocols:
• As a general rule, chemotherapy is adjusted to
maintain TWC at 2 - 3 X10^9/L and ANC at or
more than 0.75 X 10^9/L.
• If TWC drop to levels of 1-2 X10^9/L and ANC
to levels of 0.5 -0.75 x 10^9 /L or platelet
level at 50-100 x 10^9/L, reduce tablet 6-
Mercaptopurine (6MP) and oral methotrexate
(MTX) normal dose by 50%.
 Complications
Complications considered as oncologic emergencies can be seen
before, during and after treatment. These include:
❖ Hyperleucocytosis at presentation.
❖ Superior vena caval obstruction.
❖ Tumor lysis syndrome leading on to renal failure.
❖ Sepsis.
❖ Bleeding.
❖ Thrombosis.
❖ Typhlitis.
❖ CNS manifestations: Cord compression, neuropathy, encephalopathy
and seizures.
❖ Bone Marrow Suppression caused by chemotherapy
❖ Bleeding and significant anaemia.
❖ Bacterial and fungal infections
 Prognosis
• Overall cure rates for childhood ALL are now over 80% but it
depends among others on the prognostic groups, clinical and
laboratory features, treatment in centres with paediatric oncologist
and special diagnostics, use of standard treatment protocols and
also the level of supportive care available.
• Unfavourable if:
Clinical features indicating high risk:
- Age > 10 years old and infants.
-WBC count at diagnosis > 50000/mL.
• Molecular characteristics of the leukaemic blasts, e.g. Presence of
abnormal cytogenetics with oncogenes producing abnormal fusion
proteins e.g. Philadelphia chromosome t(9;22)(q34;q11); BCR-
ABL;P185BCR-ABL tyrosine kinase.
• Poor response to the induction chemotherapy
- Day 8 peripheral blast cell count > 1000 x 10^9/L.
-Day 33 BMA not in remission