Paed Haematology and Oncology Lecture - · PDF filePaediatric Haematology and ... Second...
Transcript of Paed Haematology and Oncology Lecture - · PDF filePaediatric Haematology and ... Second...
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