Paediatric Haematology and Paediatric Haematology and

OncologyOncology

All in One hour!All in One hour!

Dr Nigel CoadDr Nigel Coad

Anaemia Anaemia

Normal RangesNormal Ranges

AnaemiaAnaemia

CausesCauses�� PhysiologicalPhysiological

–– Normal babies, more marked in Normal babies, more marked in PrematuresPrematures

�� Impaired ProductionImpaired Production

–– Reduced Haematinics (Reduced Haematinics (IRONIRON, B12, , B12, FolateFolate) )

–– Bone marrow failureBone marrow failure

�� DyserythropoesisDyserythropoesis ieie ThalassaemiaThalassaemia

�� AplasiaAplasia, Leukaemia,, Leukaemia,

�� Anaemia of chronic diseaseAnaemia of chronic disease

�� Increased Breakdown Increased Breakdown ieie HaemolysisHaemolysis

�� Increased LossIncreased Loss--unusualunusual

Iron deficiencyIron deficiencyFeaturesFeatures

Presents in Infancy and ToddlersPresents in Infancy and Toddlers

AsiansAsians

Pallor, Lethargy, PicaPallor, Lethargy, Pica

InfectionsInfections

Poor school performancePoor school performance

InvestigationInvestigation

Low Low HbHb, MCV, , MCV, film,Ferritinfilm,Ferritin

Exclude other causes of Exclude other causes of

microcytosismicrocytosis

Iron deficiencyIron deficiency

�� DIETRYDIETRY

–– Infants and Toddlers, Infants and Toddlers, espesp AsiansAsians

�� fussy eatersfussy eaters

�� high milk intakehigh milk intake

�� high requirementshigh requirements

�� prematurityprematurity

�� MalabsorptionMalabsorption

�� Increased lossIncreased loss

–– GIT bleeding, menstruationGIT bleeding, menstruation

Management of Iron DeficiencyManagement of Iron Deficiency

�� Advice re DietAdvice re Diet

�� Give Iron supplements and continueGive Iron supplements and continue

�� Follow up to check responseFollow up to check response

�� Investigate underlying pathology?Investigate underlying pathology?

–– malabsorptionmalabsorption

–– blood lossblood loss

�� Rarely need transfusion or Rarely need transfusion or parenteralparenteral

IronIron

HaemolysisHaemolysis

�� Congenital or Congenital or AquiredAquired

�� Intrinsic or ExtrinsicIntrinsic or Extrinsic

FeaturesFeatures

Anaemia, Jaundice, Anaemia, Jaundice, SplenomegalySplenomegaly, ,

Increased Increased reticulocytereticulocyte countcount

Level of Level of HbHb depends on balance between Production depends on balance between Production

(marrow activity and haematinic supply) and breakdown(marrow activity and haematinic supply) and breakdown

Causes of HaemolysisCauses of Haemolysis

IntrinsicIntrinsic

�� Membrane defectsMembrane defects–– Hereditary Hereditary SpherocytosisSpherocytosis, ,

ElliptocytosisElliptocytosis

�� Abnormal HaemoglobinAbnormal Haemoglobin–– Sickle cellSickle cell

–– ThalassaemiaThalassaemia

�� Enzyme defectEnzyme defect–– G6PDG6PD

–– PyruvatePyruvate KinaseKinase deficiencydeficiency

ExtrinsicExtrinsic

�� Haemolytic Disease of Haemolytic Disease of

NewbornNewborn

�� AutoimmuneAutoimmune

�� Drug inducedDrug induced

�� Haemolytic Haemolytic UraemicUraemic

syndromesyndrome

Hereditary Hereditary SpherocytosisSpherocytosis

�� AutosomalAutosomal dominantdominant

�� Chronic Anaemia, Jaundice and Chronic Anaemia, Jaundice and

SplenomegalySplenomegaly

�� Crises precipitated by infectionCrises precipitated by infection

�� Management:Management:

–– FolateFolate supplementssupplements

–– SplenectomySplenectomy�� benefits and hazardsbenefits and hazards

Sickle cell AnaemiaSickle cell Anaemia�� Mainly African, Middle East, AsiaMainly African, Middle East, Asia

�� Sickle Haemoglobins S, C, D, E Sickle Haemoglobins S, C, D, E

�� Substitutions in Substitutions in ßß globinglobin chainchain

�� AutosomalAutosomal RecessiveRecessive

�� Normal Normal AAAA

�� Carrier/Trait Carrier/Trait AS, ACAS, AC

�� Homozygous Sickle AnaemiaHomozygous Sickle Anaemia

–– SS, SC, SDSS, SC, SD

–– Sickle/Sickle/thalthal

–– Minor variantsMinor variants CC, DD, EE CC, DD, EE

Sickle cell AnaemiaSickle cell Anaemia�� HeterozygotesHeterozygotes AsymptomaticAsymptomatic

�� Sickle PresentationSickle Presentation

–– Antenatal/Newborn screeningAntenatal/Newborn screening

–– Chronic anaemia 6Chronic anaemia 6--8g/dl8g/dl

–– CrisesCrises

�� PAIN limbs, chest or abdomen precipitated byPAIN limbs, chest or abdomen precipitated by

Cold, Hypoxia, Infection, Dehydration, AcidosisCold, Hypoxia, Infection, Dehydration, Acidosis

�� Falling Falling HbHb

�� Other types of crisisOther types of crisis

–– AplasticAplastic, , SplenicSplenic sequestrationsequestration

Sickle cell Anaemia Sickle cell Anaemia

ComplicationsComplications�� Anaemia usually 6Anaemia usually 6--8g/dL8g/dL

–– Poor growthPoor growth

–– Delayed pubertyDelayed puberty

�� Recurrent painful crises Recurrent painful crises

�� SplenicSplenic infarction infarction

–– hyposplenismhyposplenism

–– Infection overwhelming sepsisInfection overwhelming sepsis

�� 10% Stroke10% Stroke

�� Aseptic necrosis of femoral head Aseptic necrosis of femoral head

�� PriapismPriapism

Sickle cell AnaemiaSickle cell Anaemia

ManagementManagement

�� Prevention Prevention

–– AN diagnosisAN diagnosis

�� ProphylaxisProphylaxis

–– FolateFolate

–– Antibiotics, ImmunizationAntibiotics, Immunization

–– Education avoid cold, infection, dehydrationEducation avoid cold, infection, dehydration

–– Self management at homeSelf management at home

�� CrisesCrises

–– IV fluids, Antibiotics, AnalgesiaIV fluids, Antibiotics, Analgesia

Bruising and BleedingBruising and Bleeding

�� TraumaTrauma-- Accidental and NonAccidental and Non--AccidentalAccidental

�� Vascular Vascular

�� PlateletsPlatelets

�� Coagulation systemCoagulation system

Bleeding DisordersBleeding Disorders

Vascular HSP, Scurvy,

Erlers Danlos

Bruising, Purpura

Epistaxes, GIT bleeds,

stop on pressure

Platelets ITP, Leukaemia

Von Willibrands

Aspirin

Bruising, Purpura

Epistaxes, GIT bleeds,

stop on pressure

Coagulation Haemorrhagic Disease of Newborn

Haemophilia

Delayed bleeding

Deep bleeds

Muscle, joints

Pressure fails to stop

Bleeding DisordersBleeding Disorders

HistoryHistory

�� Pattern of Bruising/bleedingPattern of Bruising/bleeding

–– Recurrent Recurrent epistaxesepistaxes commoncommon

–– Easy bruising non specificEasy bruising non specific

–– Most children have limb bruisesMost children have limb bruises

�� Incidents recalled Incidents recalled

–– cicumcisioncicumcision, tonsillectomy, dental , tonsillectomy, dental

extractionextraction

�� Family historyFamily history

�� DrugsDrugs

�� Recent InfectionRecent Infection

Bleeding DisordersBleeding Disorders

ExaminationExamination

�� Sick or wellSick or well

�� Pattern of Pattern of petechiae/purpura/bleedingpetechiae/purpura/bleeding

�� Congenital MalformationsCongenital Malformations

�� SkinSkin

�� SplenomegalySplenomegaly

InvestigationsInvestigations

�� Platelet Count+ FBCPlatelet Count+ FBC

�� PTTPTT

–– Factors XII, XI, X, IX, VIII, V, IIFactors XII, XI, X, IX, VIII, V, II

�� PTPT

–– Factors X, VII, V, IIFactors X, VII, V, II

�� Bleeding TimeBleeding Time

Immune Immune ThrombocytopaenicThrombocytopaenic

PurpuraPurpura (ITP)(ITP)�� Usually young childrenUsually young children

�� Post viralPost viral

�� Recover spontaneouslyRecover spontaneously-- weeks to weeks to

monthsmonths

�� Rarely dangerous, but looks dramaticRarely dangerous, but looks dramatic

�� Nothing else abnormal Nothing else abnormal

–– No spleen, anaemia or No spleen, anaemia or neutropaenianeutropaenia

�� No treatmentNo treatment

–– Rarely need steroids, Immunoglobulin or Rarely need steroids, Immunoglobulin or

SplenectomySplenectomy

HaemophiliaHaemophilia

�� Deficiency of Factor VIII, Abnormal PTTDeficiency of Factor VIII, Abnormal PTT

�� X linked recessiveX linked recessive-- boysboys

�� Prolonged bleedingProlonged bleeding

�� Muscle bleedsMuscle bleeds

�� Joint bleeds > Arthritis and deformityJoint bleeds > Arthritis and deformity

�� Treatment Factor VIIITreatment Factor VIII

–– Complications of treatmentComplications of treatment

Cancer in ChildrenCancer in Children

Incidence 1500 children yearly in UKIncidence 1500 children yearly in UK

150 yearly in W Midlands150 yearly in W Midlands

Prevalence 1 in 600 childrenPrevalence 1 in 600 children

ieie approximately 100 children in Coventryapproximately 100 children in Coventry

Causes of death in UK childrenCauses of death in UK children

CauseCause BoysBoys GirlsGirls TotalTotal

No.No. %% No.No. %% No.No. %%

CancerCancer 151151 1919 109109 1717 260260 1818

AccidentAccident 155155 1919 8383 1313 238238 1717

CNS diseaseCNS disease 106106 1313 8686 1414 192192 1313

Malformations etcMalformations etc 6969 99 6868 1111 137137 1010

Respiratory systemRespiratory system 7070 99 5454 99 124124 99

InfectionsInfections 4646 66 4242 77 8888 66

CardiovascularCardiovascular 4343 55 4242 77 8585 66

OtherOther 171171 2121 144144 2323 319319 2222

TotalTotal 812812 100100 628628 100100 14401440 100100

http://info.cancerresearchuk.org/cancerst

ats/childhoodcancer

23

AetiologyAetiology

Unknown for most childrenUnknown for most children

The Knudson 2 hit hypothesisThe Knudson 2 hit hypothesis

GeneticGenetic Familial cancer syndromesFamilial cancer syndromes

NeurofibromatosisNeurofibromatosis

WilmsWilms

TwinsTwins

EnviromentalEnviromental-- RadiationRadiation

InfectionsInfections--HTLV, EBVHTLV, EBV

Incidence of common tumoursIncidence of common tumours

Childhood Cancer SurvivalChildhood Cancer Survival

Reasons for improved survivalReasons for improved survival

Not just about the drugs!Not just about the drugs!

Aim to maximise survival and minimise side effectsAim to maximise survival and minimise side effects

Referral to Regional Paediatric Oncology CentresReferral to Regional Paediatric Oncology Centres

Networks with shared care centresNetworks with shared care centres

Large multiLarge multi--centre trialscentre trials

Better and more individualised chemotherapy, Better and more individualised chemotherapy,

radiotherapy and surgeryradiotherapy and surgery

Improved supportive treatmentImproved supportive treatment

Nutrition, Antibiotics, Blood productsNutrition, Antibiotics, Blood products

Education of medical and nursing staffEducation of medical and nursing staff

Acute Side EffectsAcute Side Effects

Supportive CareSupportive Care

�� VomitingVomiting

�� NutritionNutrition

�� PancytopaeniaPancytopaenia

–– Febrile Febrile NeutropaeniaNeutropaenia�� Circulatory supportCirculatory support

�� IV fluidsIV fluids

�� IV broad spectrum antibioticsIV broad spectrum antibiotics

–– Blood and Platelet TransfusionsBlood and Platelet Transfusions

Long Term Side EffectsLong Term Side Effects

The cost of cureThe cost of curePsychologicalPsychological

Family and socialFamily and social

RadiotherapyRadiotherapy

Growth particularly CNS RTGrowth particularly CNS RT

Intellectual Intellectual

EndocrineEndocrine

Puberty Puberty

FertilityFertility

SurgerySurgery--CNS and boneCNS and bone

Second malignancies 4%Second malignancies 4%

Chemotherapy specific Chemotherapy specific

SteroidsSteroids

Cardiac and RenalCardiac and Renal

FertilityFertility

LymphadenopathyLymphadenopathy

�� ““Thank you for seeing this 5 year old with Thank you for seeing this 5 year old with

lump on her neck left side. The lump gets lump on her neck left side. The lump gets

bigger and smaller but doesnbigger and smaller but doesn’’t disappeart disappear””

LymphadenopathyLymphadenopathyGrowth of lymphoid system maximum in preschool childrenGrowth of lymphoid system maximum in preschool children

�� Physiological/ReactivePhysiological/Reactive�� Variable in size, bigger with infectionsVariable in size, bigger with infections

�� May be local infectionMay be local infection

�� Painful, tenderPainful, tender

�� MobileMobile

�� PathologicalPathological�� Hard, fixed, non tender, progressive enlargementHard, fixed, non tender, progressive enlargement

�� Possible ALL, Possible ALL, HodgkinsHodgkins, and Non , and Non HogkinsHogkins LymphomaLymphoma

�� May need FBC, May need FBC, MonospotMonospot, Chest XR, , Chest XR, MantouxMantoux

�� Distinguish by biopsyDistinguish by biopsy

Acute Lymphoblastic Acute Lymphoblastic

LeukaemiaLeukaemiaMost common malignancy in childhood Most common malignancy in childhood

Peak age 4Peak age 4--7yrs7yrs

Prognosis 80% curePrognosis 80% cure

Clinical FeaturesClinical Features

–– AnaemiaAnaemia

–– InfectionInfection

–– BleedingBleeding

–– Bone painBone pain

–– LymphadenopathyLymphadenopathy

–– HepatosplenomegalyHepatosplenomegaly

ALLALL-- Making the diagnosisMaking the diagnosis

Blood countBlood count

AnaemiaAnaemia

WCC up or downWCC up or down

NeutropaeniaNeutropaenia

ThrombocytopaeniaThrombocytopaenia

Blast cellsBlast cells

MarrowMarrow

LPLP

ALL ALL -- TreatmentTreatmentGood Prognostic factorsGood Prognostic factors

Age 2Age 2--1010

FemaleFemale

WCC<50WCC<50

No CNS diseaseNo CNS disease

Classified also on cell type: Common, B and T cellClassified also on cell type: Common, B and T cell

Allocated into risk groups based on prognostic featuresAllocated into risk groups based on prognostic features

Treatment escalatedTreatment escalatedPoor initial responsePoor initial response

Presence of Presence of ‘‘Minimal Residual DiseaseMinimal Residual Disease’’

4 main treatment phases:4 main treatment phases:InductionInduction

Consolidation and CNS treatmentConsolidation and CNS treatment

IntensificationIntensification

MaintenanceMaintenance Girls 2 yrsGirls 2 yrs

Boys 3 yrsBoys 3 yrs

Brain TumoursBrain Tumours

Most common solid Most common solid

tumourtumour

Peak age 5Peak age 5--9 yrs9 yrs

Usually primary and Usually primary and

infratentorialinfratentorial

Prognosis variablePrognosis variable

usually about 70%usually about 70%

High residual morbidityHigh residual morbidity

Brain Tumour Symptoms and SignsBrain Tumour Symptoms and Signs�� Raised Intracranial PressureRaised Intracranial Pressure

Early morning/night Early morning/night

HeadacheHeadache

VomitingVomiting

PapillodemaPapillodema

DrowsinessDrowsiness-- latelate

School FailureSchool Failure-- subtlesubtle

�� Focal signs/symptomsFocal signs/symptoms

Ataxia, slurred speechAtaxia, slurred speech

HemiplegiaHemiplegia

DiplopiaDiplopia

ConvulsionsConvulsions

Precocious PubertyPrecocious Puberty

Brain TumourBrain Tumour-- SitesSites

Juvenile Juvenile AstrocytomaAstrocytoma

CraniopharygiomaCraniopharygioma

Primitive Primitive NeuroectodermalNeuroectodermal

Tumours:Tumours:

((EpendymomaEpendymoma))

((MedulloblastomaMedulloblastoma))

Brainstem Brainstem GliomaGlioma

Cervical Cervical GliomaGlioma

Brain Tumour TreatmentBrain Tumour Treatment

Early diagnosis and urgent referralEarly diagnosis and urgent referral

Emergency treatment Emergency treatment DexamethasoneDexamethasone

Surgery Surgery -- can be difficultcan be difficult

RadiotherapyRadiotherapy-- side effectsside effects

ChemotherapyChemotherapy--limited valuelimited value

ThalassaemiaThalassaemia

�� Reduced Reduced globinglobin chain synthesischain synthesis

–– Normal Normal αα2 2 ββ22

–– ββ ThalThal HbHb F (F (αα and and γγ) and ) and HbHb A2 (A2 (αα and and δδ))

–– αα ThalThal 4 4 allesalles

�� loss 1 or 2 loss 1 or 2 asymtomaticasymtomatic

�� loss 3or 4 loss 3or 4 HbHb H H ββ44

ββ ThalassaemiaThalassaemia

�� ββ Thalassaemia MinorThalassaemia Minor

–– asyptomaticasyptomatic

–– Mild anaemia, low MCV, Raised Mild anaemia, low MCV, Raised HbHb A2A2

�� ββ Thalassaemia MajorThalassaemia Major

–– Progressive Severe Anaemia, low MCV, Progressive Severe Anaemia, low MCV, HbHb F F

and A2and A2

–– Jaundice (Jaundice (splenomegalysplenomegaly))

–– Failure to thriveFailure to thrive

–– Skeletal DeformitySkeletal Deformity

–– Delayed pubertyDelayed puberty

–– Death early teens/adulthoodDeath early teens/adulthood

ββ ThalassaemiaThalassaemia

ManagementManagement

�� Genetic Counselling, AN diagnosisGenetic Counselling, AN diagnosis

�� Regular blood transfusionRegular blood transfusion

�� Complications of Iron overload Complications of Iron overload

–– Liver, Heart, Pancreas, Liver, Heart, Pancreas, EndocrinopathyEndocrinopathy

�� Iron Iron chelationchelation

�� Bone Marrow TransplantationBone Marrow Transplantation

Von Von WillibrandWillibrand’’ss DiseaseDisease�� AutosomalAutosomal dominantdominant

�� Less severe than haemophilia, possibly 1% of Less severe than haemophilia, possibly 1% of

populationpopulation

�� VW FactorVW Factor

–– secreted by endothelium /plateletssecreted by endothelium /platelets

–– Carrier for FVIII:CCarrier for FVIII:C

–– Facilitates platelet adhesionFacilitates platelet adhesion

�� TestsTests

–– Prolonged Bleeding time, PTT, Prolonged Bleeding time, PTT,

–– Low FVIII:C, Low FVIII:C, vWFvWF, , RistocetinRistocetin Cofactor AssayCofactor Assay

�� TreatmentTreatment

–– DDAVP, Factor VIIIDDAVP, Factor VIII

Non HodgkinNon Hodgkin’’s Lymphomas Lymphoma

Tumour of lymphoid tissueTumour of lymphoid tissue

70% cure70% cure

Prognosis depends on stagePrognosis depends on stage

T and B cell TypesT and B cell Types

LymphadenopathyLymphadenopathy

Chest Chest mediastinalmediastinal nodes, pleural nodes, pleural

effusionseffusions

HepatosplenomegalyHepatosplenomegaly

AscitesAscites

Treatment ChemotherapyTreatment Chemotherapy

HodgkinHodgkin’’s Diseases Disease

Tumour of Lymphoid tissueTumour of Lymphoid tissue

Prognosis 50Prognosis 50--95% depending in stage95% depending in stage

Most children present early and have excellent Most children present early and have excellent

prognosisprognosis

Cervical Cervical lymphadenopathylymphadenopathy

Night sweats, fever, weight lossNight sweats, fever, weight loss

BiopsyBiopsy

Staging importantStaging important-- CT Chest and Abdomen CT Chest and Abdomen

Combination chemotherapyCombination chemotherapy-- most childrenmost children

RadiotherapyRadiotherapy-- for localised or advanced diseasefor localised or advanced disease

NeuroblastomaNeuroblastoma

Tumour of sympathetic chainTumour of sympathetic chain

Arises in chest or abdomen,adrenals rarely in neck Arises in chest or abdomen,adrenals rarely in neck

or eyeor eye

Highly malignant spread to bone, liver and locallyHighly malignant spread to bone, liver and locally

Prognosis depends on stage,most present latePrognosis depends on stage,most present late

Typically about 25% survivalTypically about 25% survival

Unwell toddler bone pain, abdominal swellingUnwell toddler bone pain, abdominal swelling

Massive abdominal massMassive abdominal mass

Diagnosis Abdominal ultrasoundDiagnosis Abdominal ultrasound

Urine Urine CatecholaminesCatecholamines

Combination chemotherapy, surgery and

WilmWilm’’ss TumourTumour

Renal tumourRenal tumour-- NephroblastomaNephroblastoma

Toddlers 2Toddlers 2--5yr old5yr old

Excellent prognosis >80% cureExcellent prognosis >80% cure

Most localised to kidneyMost localised to kidney

Spread locally,invades veins, rarely to lungsSpread locally,invades veins, rarely to lungs

Presents as a well child with abdominal mass, Presents as a well child with abdominal mass,

pain or pain or haematuriahaematuria

Treatment depends on stageTreatment depends on stage

Surgery or chemotherapy occasionally Surgery or chemotherapy occasionally

radiotherapyradiotherapy