英Acute Lymphoblastic Leukemia.ppt

ChildhoodAcuteLymphoblasticLeukemia:RiskStratificationinDevelopingCountries,ShripadBanavaliMD(Med;Bom),BC(Ped;USA),BE(Hem-Onc;USA)TataMemorialHospitalbanavali_2000,AcuteLymphoblasticLeukemia,Mostcommonformofchildhoodcancer.TreatmentofALListruesuccessstoryofmodernoncology.,KeyComponentsofSuccessfulTherapy,Clinicaltrials;Co-operativegroupsEmpiricmulti-agentCNStherapyPre-symptomaticCNStherapyPost-inductionintensificationAnti-metabolitetherapyRe-induction/re-consolidationRiskadaptedtherapy,ALL:L1,L2,L3,PAS,MultiplexRT-PCRinBlineageALL,MORPHOLOGICALREMISSION(98%)MorphologycannotdiscriminatebetweenpatientswithHRorLRofrelapse.Moresensitivetechniquesneededtodetectsmallnumbersofmalignantcellsduringandaftertreatment.DetectionofMRD(IPandRT-PCR).MOLECULARREMISSION(?%),WhatisdetectionofMRD,WhatisdetectionofMRD,Itisnothingbutdetectionoftheclonesofcellsresistanttothechemotherapygiven.,MRD:StudyofResistanceinALL,Resistancecanalsobestudiedby:-(1)MTTin-vitroAssayPred+Asp+VCRDrugresistanceprofile3yrDFS100%Mostsensitiveprofile(20%pts)84%Inter.sensitiveprofile(40%pts)43%Leastsensitiveprofile(40%pts),MRD:StudyofResistanceinALL,Resistancecanalsobestudiedin-vivoby:-(2)D7blastcountpostexposuretoPred+1doseofIT-MTX(3)D15BMblast%,EstimationofMRD,Flowcytometry:(2)RT-PCR:,TreatmentofChildhoodALL,TOPPRIORITYPREVENTIONOFRELAPSE,ALL-ChallengesForDevelopedCountriesClinicaltrials,Despitesuccess,25%ofchildrenrelapse.Intensifytherapyforthosewhoneedorwillbenefitfromit.Manyofthosewhoarecuredareover-treatedMinimizesideeffectsLittleprogresshasbeenmadeinthetreatmentofcertainveryhighriskgroups(Ph+,infantsandrelapse)Developnewtreatmentoptions,PEDIATRICONCOLOGY:FACTS,IndiaU.S.A.Newcases/yr44,00012,400Rx,curativeintent25%100%Curerate,adequ.Rxed50%70%Overallcurerate12%70%RxedonCo-opGroups1%98%,HematologicalcancersinIndiaAverageAnnualAgestandardizedincidencerateper100,000persons(1990-1996),RegionLymphoidleukemiaMyeloidleukemiaMFMFDelhi1.9Mumbai1.6Bangalore1.7Chennai1.71.01.41.2Bhopal1.4Barshi1.0,MedicalOncology,vol.19,141-150,2002,RxofALL:THETMHEXPERIENCE,V+P1-22%V+P+DoxoorL-Asp2-32%VACP3-30%1.Advanietal:AmJHematol15:35,19832.Advanietal:IndJCancer26:180,19893.Advanietal:AmJHematol39:242,19924.Advanietal:AnnOnc10:167,1999,Advanietal.AnnOncol1999,Advanietal.AnnOncol1999,Clinicalcharacteristicsinrelationshiptoeventfreesurvivalbyparticipatingcenter.Resultsofmulti-variateanalysis.,CALLA+ACUTELYMPHOBLASTICLEUKEMIACHANGINGINCIDENCEOVER3DECADES,T-ACUTELYMPHOBLASTICLEUKEMIACHANGINGINCIDENCEOVER3DECADES,FrequenciesofthemajorsubgroupsofPrecursorBcellALLinIndianchildrendifferfromtherest.SirajAK,etal.Leukemia2003;17:1192-93,n=259India(%)USA(%)Europe(%)TEL-AML-172223mBCR-ABL*52.21.8ELA-PBX173.81.6MLL-AF401.21.6,*GuiterrezMI,etal.JMolDiagnostics2005;7:40-47,CHENNAI,DELHI,xMUMBAI,ChildhoodAcuteLymphoblasticLeukemiaResultsofMCP-841inotherCentres,ALL:FUTUREPLANSCLINICAL,NewALLprotocolCollaborationwithINCTRSalientfeaturesMoreContinuousCTMoreChemoin1styearBothInj.Iggenerearrangements;knowntranslocations.Individualprimers.Expertisenotavailableatallcentres.,CantherebeasimplewaytoestimateMRD?,RealTimeAnalysisofTerminalDeoxyTransferaseGeneExpression:AconvenientmarkerforMinimalResidualLeukemiaBuR,BelgaumiA,TimsonG,BanavaliS,AlMahir,BhatiaK,GutierrezMI.,TDTexpressionbyallALLblastsNotexpressednormallyinPBEstimationofTDTinPBbyRealtimePCR,ALL:“CoreBiology”LabAssessmentOfComponentsOfCureInDevelopingCountries,Realtimereferencelaboratorysystemforriskbasedclassification.MRDstudies:usingsingleparameter,e.g.TDTUsingPBAtdiagnosis;Atweek4&6(8),ALL:“CoreBiology”LabAssessmentOfComponentsOfCureInDevelopingCountries,Allsamplestobesenttoacentrallabbycourier.MRDstudiesbasedonsingleparameter,e.g.TDT.5-7dayturnaroundtime.Resultssentbye-mail.Remainingsampletobestoredforfuturestudies.,WhatIsTheBestWayToRiskStratifyChildrenWithALLInDevelopingCountries?,Oneparameter(Notmultiplelikeclinical,IP,DI,Cytogen,Mol,MRD)MRDEstimationSimplestversionusingsingleparameterFunctionalassay,ManagementofChildhoodALL,CommonStandardRem.IndProtocol,EstimationofMRDatD29/D43,0.01%,1%,?LessintensiveRx?Shorterduration,D.D.I,Allo.BMTInvestigationalTherapies,ChildhoodCancersareCURABLEPROVIDEDTHEYARE.diagnosedearlydiagnosedproperlytreatedappropriately,ALLTEAM,ClinicalLabStudiesINCTRCollaborationDr.S.D.BanavaliDr.C.N.NairDr.IanMagrathDr.P.A.KurkureDr.AshokKumarMs.MelissaAddeDr.B.AroraMr.SashikantDr.KishoreBhatiaDr.S.K.PaiDr.A.ChouguleDr.MarinaGutierrezDr.P.M.ParikhDr.P.M.ParikhDr.R.BhagwatDr.S.BarbhayaMSWDept.Dr.A.VoraDr.S.KamathMr.M.A.P