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

AnaemiaAnaemiaCausesCauses

PhysiologicalPhysiological Impaired ProductionImpaired Production

– Bone marrow failureBone marrow failure Dyserythropoesis ie ThalassaemiaDyserythropoesis ie Thalassaemia Aplasia, Leukaemia,Aplasia, Leukaemia, Anaemia of chronic diseaseAnaemia of chronic disease

– Reduced Haematinics (Iron, B12, Folate)Reduced Haematinics (Iron, B12, Folate) Increased Breakdown ie HaemolysisIncreased Breakdown ie Haemolysis Increased Loss-unusualIncreased Loss-unusual

Iron deficiencyIron deficiencyFeaturesFeatures

Presents in Infancy and ToddlersPresents in Infancy and Toddlers

AsiansAsians

Pallor, Lethargy, PicaPallor, Lethargy, Pica

Risk of InfectionRisk of Infection

Poor school performancePoor school performance

Functional murmerFunctional murmer

InvestigationInvestigation

Low Hb, MCV, FerritinLow Hb, MCV, Ferritin

Exclude other causes of Exclude other causes of microcytosismicrocytosis

Iron deficiencyIron deficiency

DietaryDietary– Infants and Toddlers, esp AsiansInfants and Toddlers, esp Asians

fussy eatersfussy eaters high milk intakehigh milk intake high requirementshigh requirements prematurityprematurity

MalabsorptionMalabsorption Increased lossIncreased loss

– GIT bleeding, menstruationGIT bleeding, menstruation

Treatment of Iron deficiencyTreatment 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 pathologyInvestigate underlying pathology

– malabsorptionmalabsorption– blood lossblood loss

Rarely need transfusion or parenteral Rarely need transfusion or parenteral IronIron

HaemolysisHaemolysis

Congenital or AquiredCongenital or Aquired Intrinsic or ExtrinsicIntrinsic or Extrinsic

FeaturesFeaturesAnaemia, Jaundice, Splenomegaly, BilirubinuriaAnaemia, Jaundice, Splenomegaly, Bilirubinuria

Increased ReticsIncreased ReticsLevel of Hb depends on balance between Production (marrow Level of Hb depends on balance between Production (marrow

activity and haematinic supply) and breakdownactivity and haematinic supply) and breakdown

Causes of HaemolysisCauses of Haemolysis

IntrinsicIntrinsic Membrane defectsMembrane defects

– Hereditary Spherocytosis, Hereditary Spherocytosis, ElliptocytosisElliptocytosis

Abnormal HaemoglobinAbnormal Haemoglobin– Sickle cellSickle cell– ThalassaemiaThalassaemia

Enzyme defectEnzyme defect– G6PDG6PD– Pyruvate Kinase deficiencyPyruvate Kinase deficiency

ExtrinsicExtrinsic Haemolytic Disease of Haemolytic Disease of

NewbornNewborn AutoimmuneAutoimmune Drug inducedDrug induced Haemolytic Uraemic Haemolytic Uraemic

syndromesyndrome

Hereditary SpherocytosisHereditary Spherocytosis

Anaemia, Jaundice and SplenomegalyAnaemia, Jaundice and Splenomegaly Autosomal dominantAutosomal dominant Crises precipitated by infectionCrises precipitated by infection Folate supplementsFolate supplements Splenectomy Splenectomy

– benefits and hazardsbenefits and hazards

Sickle cell AnaemiaSickle cell Anaemia Mainly African, Middle East, AsiaMainly African, Middle East, Asia substitutions in ß globin chainsubstitutions in ß globin chain Autosomal RecessiveAutosomal Recessive

Normal Normal AAAA Carrier/Trait Carrier/Trait AS, ACAS, AC Sickle AnaemiaSickle Anaemia SS, SC, SDSS, SC, SD Sickle ThalSickle Thal VariantsVariants CC, DD, EE CC, DD, EE

Sickle cell AnaemiaSickle cell Anaemia Heterozygotes AsymptomaticHeterozygotes Asymptomatic

Sickle PresentationSickle Presentation– screeningscreening– anaemia 6-8g/dlanaemia 6-8g/dl– CrisesCrises

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

Hypoxia, Infection, Dehydration, AcidosisHypoxia, Infection, Dehydration, Acidosis

Other types of crisisOther types of crisis– Aplastic, Splenic sequestrationAplastic, Splenic sequestration

Sickle cell Anaemia Sickle cell Anaemia ComplicationsComplications

AnaemiaAnaemia Splenic infarction hyposplenismSplenic infarction hyposplenism Infection overwhelming sepsisInfection overwhelming sepsis 10% Stroke10% Stroke Aseptic Necrosis of Femoral Head Aseptic Necrosis of Femoral Head Poor Growth, delayed pubertyPoor Growth, delayed puberty PriapismPriapism Leg UlcersLeg Ulcers

Sickle cell AnaemiaSickle cell AnaemiaManagementManagement

Prevention Prevention – AN diagnosisAN diagnosis

ProphylaxisProphylaxis– FolateFolate– Antibiotics, ImmunizationAntibiotics, Immunization– Avoid Cold infection dehydrationAvoid Cold infection dehydration

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

Bruising and BleedingBruising and Bleeding

TraumaTrauma- Accidental and Non-Accidental- Accidental and Non-Accidental

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 DisordersHistoryHistory

Pattern of Bruising/bleedingPattern of Bruising/bleeding– Recurrent epistaxes commonRecurrent epistaxes common

– Easy bruising non specificEasy bruising non specific

– Most children have limb bruisesMost children have limb bruises

Incidents recalled Incidents recalled – cicumcision, tonsillectomy, dental extractioncicumcision, tonsillectomy, dental extraction

Family historyFamily history DrugsDrugs Recent InfectionRecent Infection

Bleeding DisordersBleeding DisordersExaminationExamination

Sick or wellSick or well Pattern of petechiae/purpura/bleedingPattern of petechiae/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 Thrombocytopaenic Immune Thrombocytopaenic Purpura (ITP)Purpura (ITP)

Usually young childrenUsually young children Post viralPost viral Recover spontaneously- weeks to monthsRecover spontaneously- weeks to months Rarely dangerous, but looks dramaticRarely dangerous, but looks dramatic Nothing else abnormal Nothing else abnormal

– No spleen, anaemia or neutropaeniaNo spleen, anaemia or neutropaenia

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 recessive- boysX linked recessive- boys 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

ie approximately 100 children in Coventryie approximately 100 children in Coventry

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

Incidence of common tumoursIncidence of common tumours

Improved SurvivalImproved Survival

Reasons for improved survivalReasons for improved survival

Referral to Regional Paediatric Oncology CentresReferral to Regional Paediatric Oncology Centres

What are the benefits?What are the benefits?

Improved understanding of disease and Improved understanding of disease and complicationscomplications

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

radiotherapy and surgeryradiotherapy and surgery

Large multi-centre trialsLarge multi-centre trials

Improved supportive treatmentImproved supportive treatment

Education of medical and nursing staffEducation of medical and nursing staff

Improved shared care with joint care standardsImproved shared care with joint care standards

Long Term Side Effects Long Term Side Effects

PsychologicalPsychological

Family and socialFamily and social

Growth particularly CNS RTGrowth particularly CNS RT

EndocrineEndocrine

Puberty Puberty

FertilityFertility

IntellectualIntellectual

Second malignanciesSecond malignancies

Chemotherapy specific Chemotherapy specific

Acute Lymphoblastic Acute Lymphoblastic LeukaemiaLeukaemia

Most common malignancyMost common malignancy

Peak age 4-7yrsPeak age 4-7yrs

Prognosis 80% curePrognosis 80% cure

Good Prognostic factorsGood Prognostic factors

Age 2-10Age 2-10

FemaleFemale

WCC<50WCC<50

No CNS diseaseNo CNS disease

Classified also on cell type Classified also on cell type Common, Common,

B and T cellB and T cell

ALL- Clinical FeaturesALL- Clinical Features

AnaemiaAnaemia

InfectionInfection

BleedingBleeding

Bone painBone pain

LyphadenopathyLyphadenopathy

HepatosplenomegalyHepatosplenomegaly

ALL- Making the diagnosisALL- Making the diagnosis

Blood countBlood countAnaemiaAnaemia

WCC up or downWCC up or down

NeutropaeniaNeutropaenia

ThrombocytopaeniaThrombocytopaenia

Blast cellsBlast cells

MarrowMarrow

LPLP

ALL - TreatmentALL - Treatment

Stratified into risk groups A B CStratified into risk groups A B C

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 5-9 yrsPeak age 5-9 yrs

Usually primary and Usually primary and

infratentorialinfratentorial

Prognosis variablePrognosis variable

usually about 50%usually about 50%

Brain Tumour SymptomsBrain Tumour Symptoms Raised Intracranial PressureRaised Intracranial Pressure

Early morning/night Early morning/night

HeadacheHeadache

VomitingVomiting

DrowsinessDrowsiness

School FailureSchool Failure Focal signs/symptomsFocal signs/symptoms

Ataxia, slurred speechAtaxia, slurred speech

HemiplegiaHemiplegia

DiplopiaDiplopia

ConvulsionsConvulsions

Precocious PubertyPrecocious Puberty

Brain Tumour- SitesBrain Tumour- Sites

Juvenile AstrocytomaJuvenile Astrocytoma

CraniopharygiomaCraniopharygioma

Primitive Neuroectodermal Primitive Neuroectodermal Tumours:Tumours:

(Ependymoma)(Ependymoma)

(Medullobastoma)(Medullobastoma)

Brainstem GliomaBrainstem Glioma

Cervical GliomaCervical Glioma

Brain Tumour TreatmentBrain Tumour Treatment

Surgery - can be difficultSurgery - can be difficult

Radiotherapy- side effectsRadiotherapy- side effects

Chemotherapy-limited valueChemotherapy-limited value

ThalassaemiaThalassaemia

Reduced globin chain synthesisReduced globin chain synthesis– Normal Normal 2 2 22 Thal Hb F (Thal Hb F ( and and ) and Hb A2 () and Hb A2 ( and and )) Thal 4 alles Thal 4 alles

loss 1 or 2 asymtomaticloss 1 or 2 asymtomatic loss 3or 4 Hb H loss 3or 4 Hb H 44

ThalassaemiaThalassaemia Thalassaemia Minor Thalassaemia Minor

– asyptomaticasyptomatic– Mild anaemia, low MCV, Raised Hb A2Mild anaemia, low MCV, Raised Hb A2

Thalassaemia MajorThalassaemia Major– Progressive Severe Anaemia, low MCV, Hb F and A2Progressive Severe Anaemia, low MCV, Hb F and A2– Jaundice (splenomegaly)Jaundice (splenomegaly)– Failure to thriveFailure to thrive– Skeletal DeformitySkeletal Deformity– Delayed pubertyDelayed puberty– Death early teens/adulthoodDeath early teens/adulthood

ThalassaemiaThalassaemiaManagementManagement

Genetic Counselling, AN diagnosisGenetic Counselling, AN diagnosis Regular blood transfusionRegular blood transfusion Complications of Iron overload Complications of Iron overload

– Liver, Heart, Pancreas, EndocrinopathyLiver, Heart, Pancreas, Endocrinopathy

Iron chelationIron chelation Bone Marrow TransplantationBone Marrow Transplantation

Von Willibrand’s DiseaseVon Willibrand’s Disease Autosomal dominantAutosomal dominant Less severe than haemophilia, possibly 1% of populationLess severe than haemophilia, possibly 1% of population

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, vWF, Ristocetin Cofactor AssayLow FVIII:C, vWF, Ristocetin Cofactor Assay

TreatmentTreatment– DDAVP, Factor VIIIDDAVP, Factor VIII

Non Hodgkin’s LymphomaNon Hodgkin’s LymphomaTumour 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 mediastinal nodes, pleural effusionsChest mediastinal nodes, pleural effusions

HepatosplenomegalyHepatosplenomegaly

AscitesAscites

Treatment ChemotherapyTreatment Chemotherapy

Hodgkin’s DiseaseHodgkin’s DiseaseTumour of Lymphoid tissueTumour of Lymphoid tissue

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

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

Cervical lymphadenopathyCervical lymphadenopathy

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

BiopsyBiopsy

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

Combination chemotherapy- most childrenCombination chemotherapy- most children

Radiotherapy- for localised or advanced diseaseRadiotherapy- for localised or advanced disease

Neuroblastoma Neuroblastoma Tumour of sympathetic chainTumour of sympathetic chain

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

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 CatecholaminesUrine Catecholamines

Combination chemotherapy, surgery and radiotherapyCombination chemotherapy, surgery and radiotherapy

Wilm’s TumourWilm’s TumourRenal tumour- NephroblastomaRenal tumour- Nephroblastoma

Toddlers 2-5yr oldToddlers 2-5yr 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 haematuriapain or haematuria

Treatment depends on stageTreatment depends on stage

Surgery or chemotherapy occasionally Surgery or chemotherapy occasionally radiotherapyradiotherapy