Oncology & Haematology - ALL/Anaemia

Question 1

How common is childhood malignancy?

Answer 1

1 in 500 by 15 years old

Question 2

What are the common cancers in children?

Answer 2

leukaemia (all ages) - 32%
brain and spinal tumours - 24%
lymphomas (peak in adolescence and early life) - 10% 
neuroblastoma (under 6 years) - 7% 
soft tissue sarcomas - 7% 
wilms tumour (under 6 years) - 6% 
bone tumour - 4%
retinoblastoma - 3%

Question 3

What are the common presenting symptoms and signs of ALL?

Answer 3

general - malaise and anorexia
bone marrow infiltration - anaemia (lethargy), neutropenia (infection), thrombocytopenia (bruising, petechiae, nose bleeds) and bone pain
reticulo-endothelial infiltration - hepatosplenomegaly, lymphadenopathy and uncommonly superior mediastinal obstruction

Question 4

What investigations should be carried out when establishing a diagnosis of ALL?

Answer 4

FBC - low haemoglobin, thrombocytopenia and evidence of circulating leukemic blast cells

Bone marrow examination is essential to confirm diagnosis

Chest x-ray to identify mediastinal masses in T cell disease

Question 5

What are the 5 stages of treatment for ALL?

See diagram for more detail

Answer 5

1) Induction
2) Consolidation and CNS protection
3) Interim maintenance
4) Delayed intensification
5) Continuing maintenance (up to 3 years from diagnosis)

Question 6

How else is ALL managed alongside the chemotherapy?

Answer 6

correct anaemia
give platelets
treat infections
protect kidneys with allopurinol and fluids

Question 7

What is the common age for leukaemia to present?

Answer 7

80% presents at 2-5 years

Question 8

How are relapses treated?

Answer 8

high dose chemotherapy

total body irradiation and bone marrow transplantation as an alternative to conventional chemotherapy

Question 9

What are the poor prognostic factors in leukaemia?

Answer 9

Age <1 or >10
Tumour load >50x10^9/L
MLL rearrangement
Speed of response to initial chemo (persistence of leukaemic blast cells)
High minimal residual diseases assessment
Male gender
Spread to CNS

Question 10

What are the normal physiological changes affecting blood count between neonate and an adolescent?

Answer 10

haemopoiesis is the process that maintains lifelong production of haemopoietic blood cells

main site is the liver in fetal life and bone marrow in post natal life

Question 11

How is anaemia defined in infants?

Answer 11

neonate: Hb<14 (high Hb to compensate for low oxygen concentration in the fetus)
1-12 months: Hb<10
1-12years: Hb<11

Question 12

How do WCC and platelets vary in childhood?

Answer 12

WCC in neonates is higher compared with older children

Platelet count is similar to adult

Question 13

Why does iron deficiency anaemia occur in infants?

Answer 13

because addition iron is required for increase in blood volume accompanying growth and to build up the child’s stores
iron can come from breast milk

Question 14

How does iron deficiency present?

Answer 14

will not usually present until below 6-7 g/dl
child will tire easily and feed slowly
appears pale
pica

Question 15

How is iron deficiency managed?

Answer 15

dietary advice
oral supplementation
if no gain malabsorption needs to be investigated
need for blood transfusion is rare

Question 16

What occurs in folate deficiency?

Answer 16

folate is vital as provides consituents to produce red cells
macrocytic megaloblastic anaemia occurs when deficient

Question 17

Why is B12 important?

Answer 17

vital for DNA synthesis

deficiency will present in a similar way to folate deficiency

Question 18

How does malignant disease generally affect WCC?

Answer 18

drop in WCC

Question 19

How does haemolytic anaemia present?

Answer 19

reticuloendothelial hyperplasia - leading to hepatosplenomegaly
unconjugated bilirubin increase
increased urinary bilinogen

Question 20

What is haemolytic anaemia?

Answer 20

reduced red cell lifespan due to increased intravascular and extravascular (spleen and liver) destruction of RBC

Question 21

What causes haemolytic anaemia?

Answer 21

hereditary spherocytosis - mutation in the genes encoding RBC skeletal proteins

G6PD deficiency - X linked condition. Neonatal jaundice in first 3 days or acute haemolysis precipitated by infection, drugs, broad beans

Pyruvate kinase deficiency - decrease ATP causing cell to become more rigid

Question 22

What are the three main types of sickle cell disease?

Answer 22

sickle cell anaemia
HbSC disease
Sickle B-thalassaemia
Sickle trait

Question 23

What mutations of haemoglobin lead to sickle cell disease?

Answer 23

HbS mutation causes a change in aa from glut to valine - causes it to polymerise within RBC forming rigid tubular spiral bodies which deforms the red cells into a sickle shape, they have a reduced life span and become trapped in microcirculation

HbC mutation causes a change in aa from glutamic acid to lycine

Question 24

What are the clinical features of sickle cell disease?

Answer 24

• Anaemia with clinically detectable jaundice
• Infection - increased susceptibility to pneumococci and H.influenze
• Painful crises - most commonly on hands and feet
• Acute anaemia - sudden drop in haemoglobin due to haemolytic crisis
• Priapism - needs to be treated promptly
• Splenomegaly - more common in young children

Question 25

What are the homozygous and heterozygous forms sickle cell disease?

Answer 25

Sicke cell anaemia - HbS + HbS
HbSC disease - HbS + HbC
Sickle cell thalassaemia - HbS + B-thalassaemia trait
Sickle cell trait - HbS + normal B-globin gene

Question 26

How does sickle cell disease present through population screening?

Answer 26

Gurthrie test (neonatal) - early diagnosis allows penicillin prophylaxis started early infection 
Prenatal diagnosis by CVS at the end of the first trimester if parents wish to prevent birth of affected child

Question 27

What are the long term problems of sickle cell disease?

Answer 27

• short stature, delayed puberty
• stroke and cognitive problems
• adenotonsillar hypertrophy
• cardiac enlargement (from chronic anaemia)
• heart failure (from uncorrected anaemia)
• renal dysfuction
• pigmented gallstones
• leg ulcers (uncommon in children)

Question 28

How is sickle cell managed?

Answer 28

• prophylaxis with full immunisation and daily oral penicillin throughout childhood
• once daily folic acid
  avoid cold, dehydration, exercising excessively, undue stress and hypoxia
• treat acute crises with analgesia, good hydration, oxygen

Question 29

What are the two main types of B-thalassaemia?

Answer 29

1) B-thalassaemia - most severe form of disease, HbA cannot be produced because of abnormal B-globin gene
2) B-thalassaemia intermedia - milder and variable severity, B-globin mutations allow small amount of HbA and large amount of HbF
3) B thalassaemia trait - usually asymptomatic, hypochromia and microcytic red cells, mild or no anaemia

Question 30

What are the clinical features of beta thalassaemia?

Answer 30

• severe anaemia, transfusion dependent from 3-6 months of age
• failure to thrive/growth failure
• extramedullary haemopoiesis - if not treated with regular blood transfusions the hepatosplenomegaly and bone marrow expansion

Question 31

How is B-thalassaemia treated?

Answer 31

• lifelong monthly blood trasnfusions
• aim to keep haemoglobin >10 g/dl to reduce growth failure and prevent bone deformation
• repeat transfusions can cause chronic iron overload which leads to cardiac failure, liver cirrhosis, diabetes, infertility and growth failure
• all patients treated with iron chelation from 2-3 years
• if compliant 90% reach 40 years
• alternatively a bone marrow transplant is curative

Question 32

What is the cause and presentation of alpha thalassemia?

Answer 32

• alpha thalassaemia major - no alpha-globin genes
• presents in mid trimester as fetal hydrops from fetal anaemia
• fatal in utero or within hours of delivery