Oncology & Haematology - ALL/Anaemia Flashcards
How common is childhood malignancy?
1 in 500 by 15 years old
What are the common cancers in children?
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%
What are the common presenting symptoms and signs of ALL?
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
What investigations should be carried out when establishing a diagnosis of ALL?
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
What are the 5 stages of treatment for ALL?
See diagram for more detail
1) Induction
2) Consolidation and CNS protection
3) Interim maintenance
4) Delayed intensification
5) Continuing maintenance (up to 3 years from diagnosis)
How else is ALL managed alongside the chemotherapy?
correct anaemia
give platelets
treat infections
protect kidneys with allopurinol and fluids
What is the common age for leukaemia to present?
80% presents at 2-5 years
How are relapses treated?
high dose chemotherapy
total body irradiation and bone marrow transplantation as an alternative to conventional chemotherapy
What are the poor prognostic factors in leukaemia?
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
What are the normal physiological changes affecting blood count between neonate and an adolescent?
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
How is anaemia defined in infants?
neonate: Hb<14 (high Hb to compensate for low oxygen concentration in the fetus)
1-12 months: Hb<10
1-12years: Hb<11
How do WCC and platelets vary in childhood?
WCC in neonates is higher compared with older children
Platelet count is similar to adult
Why does iron deficiency anaemia occur in infants?
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
How does iron deficiency present?
will not usually present until below 6-7 g/dl
child will tire easily and feed slowly
appears pale
pica
How is iron deficiency managed?
dietary advice
oral supplementation
if no gain malabsorption needs to be investigated
need for blood transfusion is rare
What occurs in folate deficiency?
folate is vital as provides consituents to produce red cells
macrocytic megaloblastic anaemia occurs when deficient
Why is B12 important?
vital for DNA synthesis
deficiency will present in a similar way to folate deficiency
How does malignant disease generally affect WCC?
drop in WCC
How does haemolytic anaemia present?
reticuloendothelial hyperplasia - leading to hepatosplenomegaly
unconjugated bilirubin increase
increased urinary bilinogen
What is haemolytic anaemia?
reduced red cell lifespan due to increased intravascular and extravascular (spleen and liver) destruction of RBC
What causes haemolytic anaemia?
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
What are the three main types of sickle cell disease?
sickle cell anaemia
HbSC disease
Sickle B-thalassaemia
Sickle trait
What mutations of haemoglobin lead to sickle cell disease?
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
What are the clinical features of sickle cell disease?
- 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
What are the homozygous and heterozygous forms sickle cell disease?
Sicke cell anaemia - HbS + HbS
HbSC disease - HbS + HbC
Sickle cell thalassaemia - HbS + B-thalassaemia trait
Sickle cell trait - HbS + normal B-globin gene
How does sickle cell disease present through population screening?
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
What are the long term problems of sickle cell disease?
- 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)
How is sickle cell managed?
- 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
What are the two main types of B-thalassaemia?
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
What are the clinical features of beta thalassaemia?
- 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
How is B-thalassaemia treated?
- 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
What is the cause and presentation of alpha thalassemia?
- 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
