A(2)

Question 1

What is anaemia of prematurity?

Answer 1

Normocytic, normochromic, hyporegenerative anaemia in an infant associated with low serum EPO.

Question 2

What are the aetiologies of AOP?

Answer 2

Low EPO
Short RBC lifespan
Low Fe stores and blood loss intrpartum/ blood sampling induced
Rare causes: haemolysis (HODN or haemoglobinopathies), BM Suppression (Infection/ renal failure) BM failure (aplastic anaemia/ malignancy)

Question 3

How do low EPO and short RBC lifespan cause AOP?

Answer 3

EPO is initially produced in foetal liver, moves to the kidney in later stages. Liver production stimulation requires higher degree of hypoxia and anaemia than kidney production. Preterm liver is still main source -> low EPO

Short RBC lifespan: foetal RBCs with foetal Hb have shorter lifespan by 50-66%. This is because they have lower metabolism and are more sensitive to peroxidation.

Question 4

What is the epidemiology of AOP?

Answer 4

Frequency is inversely related to gestational age and BW. (50% of <32wk)

Question 5

What are the examination/ history findings of AOP?

Answer 5

Low activity which is improved by transfusion

Poor weight gain despite high calorie intake

Tachypnea, tachycardia, pallor and flow murmurs

If severe, respiratory depression, episodes of aopnea

Question 6

What are the investigations in AOP?

Answer 6

Bloods: Hb <10g/dl, normochromic normocytic normal Pl/WCC

Film: low reticulocyte count (low EPO) abnormal RBC forms, RC fragmentation.

Blood typing: check ABO/RH compatibility for transfusio

Question 7

What is the management of AOP?

Answer 7

Transfusion if any of the following: Hb<8, fail to thrive, CVS/Resp compromise, Coexisting pathologies.

Fe supplementation. NB: Recombinant EPO NOT ADVISED.

Question 8

What is the complications and prognosis of AOP?

Answer 8

Transfusion acquired reaction or infection, fluid overload, electrolyte imbalances.

Preterm infants usually started on Fe therapy for 2-3/12. Resolves by 6/12 usually.

Question 9

What is ALL?

Answer 9

Malignant clonal disease of proliferation of B and T cell progenitors.

Question 10

What is the cause of ALL?

Answer 10

Genetic lesions in leukemic clone. Karyotype 80% abnormal. B cell most common. FAB classification.

Cytogenetic abnormalities: TEL-AML1 fusion gene most common/best pgc– t(12:21). Ph chromosome in some but more common in CML. NOTCH1 mutations

Associated w/ Trisomy 21, FA, achondroplasia, ataxia tenelgectasia, xeroderma pigmentosum, X glinked agammablobulinaemia, sibling association.

Question 11

What is the epidemiology of ALL?

Answer 11

30 million/yr.

Question 12

What is the history/ exam of ALL?

Answer 12

BM failure: anaemia, infections, bruising, bleeding gums, infections.

Organ infiltration: Thymic mass, hepatsplenomegaly, testes mass, meningeal involvement causing headache nausea and CN palsies, tender bones, mediatinal compression in T cell ALL with dyspnea, lymphadenopathy.

Question 13

What are the investigations in ALL?

Answer 13

Bood: low Hb normocytic, low Pl, high WCC, high Uric acid, high LDH.

BM aspirate/biopsy: hypercellular >30%, lymphoblasts, histochemical stains, flow cytometry, cytogenetics. (Karyotype, translocations with PAS stain, acid phosphatase for T lineage).

LP for CSF analysis, CXR for mediastinal involvement, bone XR for ‘punched out’ lesions.

Question 14

What is the management of ALL?

Answer 14

Chemotherapy: remission induction phase (reduce marrow infiltration by 99%), insensification or consolidation phase (remove drug resistant residues), continuation therapy (2-2.5y).

Allogenic SCT: if Ph+ or low initial response to tx.

CNS directed radiation: only in HIGH risk.

Supportive care: antiemetics, infection prophylaxis (cotrimox for PCP) blood products/gf.

Question 15

What are the complications of ALL?

Answer 15

VTE secondary to chemotherapy. Cardiotoxicity, fertility issues, secondary malignancy (esp intracranial tumors and NHL) and relapse.

60-80% 5y survival. Poor pgx with Ph, WCC>100, T cell ALL, CNS involvement.

Question 16

What is AML?

Answer 16

Malignancy of primitive myeloid lineage white blood cells (myeloblasts) with proliferation in the BM and blood.

Question 17

How is AML classified?

Answer 17

. Classified as the following FAB:

· M0: myeloblastic with no maturation

· M1: myeloblastic with little proliferation

· M2: myeloblastic with proliferation t(8;21)

· M3: promyelocytic with coarse cytoplasmic granules (associated with DIC)

· M4: Granulocyte and monocyte differentiation (Eos: Inv(16) )

· M5: Monoblastic differentiation

· M6: Erythroblastic differentiation

· M7: Megakaryoblastic differentiation

Question 18

What is the aetiology of AML?

Answer 18

Myeloblasts, arrested at early development, with varying genetic abnormalities, hyperproliferate in the BM and blood leading to crowdout of other BM cells and BM failure.

Question 19

When may AML occur?

Answer 19

Occurs primary or secondaty to previous chemotherapy/myelodysplasia. 80% children have chromosomal abnnroamlities. 11q23 most common (MLL gene),

Associations: trisomy 21, Sweet syndrome (acute febrile neutrophilic dermatitis), constitutional trisomy 8, Swachman Diamond syndrome, FA, Toxin exposure (Ethanol, pesticides, toposisomerase III inhibitors)

Question 20

What is the epidemiology of AML?

Answer 20

More often in adults. Risk increases with age. 17% of childhood leukemias.

Question 21

What is the history and exam of AML?

Answer 21

Symptoms of BM failure: bleeding, infection, anaemic symptoms

Symptoms of tissue infiltration: Gum swelling and bleeding, lymph nodes large and pale, CNS involvement (esp. M4M5), coagulopathy

BM failure: Pallor, cardiac flow murmur, tachycardia, dyspnea. Ecchymoses, bleeding, signs of infection.

Tissue infiltration: Gum hypertrophy, skin rashes, choloma (deposit of leukemic blasts in the eye), deposits in tongue and bones.

Question 22

What investigations are done in AML?

Answer 22

Blood: FBC (low Hb, low platelets, variable WCC)

High uric acid, high LDH. Clotting studies, fibrinogen and D dimers (if DIC is suspected as per M3 form)

Blood film: AML myelocytes show cytoplasmic Auer rods.

BM film: crowdout of cells in BM, hypercellular BM 30%+blasts.

Immunophenotyping: antibodies against surface antigen for lineage.

Cytogenetics: prognostic information

Immunocytochemistry: myeloblast granules positive for Sudan black, chloroacetate esterase and myeloperoxidase. Monobladts are positive for non specific and butyrate esterase.

Question 23

What is the management of AML?

Answer 23

Emergency (DIC): FFP and platelet transfusion.

Chemotherapy: Remission induction with CNS prophylaxis –/ Consolidation à intensification –. With or without maintenance stage.

Stem cell transplant

Supportive care: central venous access, blood transfusion, infection prophylaxis.

Question 24

What are the complications of AML?

Answer 24

Relapse. Squelae of chemotherapy: infertility, cardiotoxicity.

Tumor lysis syndrome TLS: rapid cell death with initiation of chemotherapy resulting in hyperkalaemia, hyperphosphataemia, hyperuricaemia, with secondary hypocalcaemia. This leads to renal failure.

Prevention of TLS includes screening for G6PD deficiency, good hydration, Rasurbicase in high risk patinets (with high WCC>50). Allopurinol for intermediate risk (WCC 10-50)

Question 25

What is the prognosis of AML?

Answer 25

Prognosis depends on age. 50% cure rate in <60y (may be higher with stem cell transplant).

Good prognosis: t(8,21) in M2, t(15,7) M3, Inversion 16 in M4 (70-90% cure rate)

Bad prognosis: monosomy 5/7 and complex karyotypes (10-30% cure rate)