paediatric haematology and oncology all in one hour! dr nigel coad
TRANSCRIPT
Paediatric Haematology and Paediatric Haematology and OncologyOncology
All in One hour!All in One hour!
Dr Nigel CoadDr Nigel Coad
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
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