白血病英文課件

THECHILDHOODLEUKEMIA

THECHILDHOODLEUKEMIA1LeukemiaLeukemiaisadiseasecharacterizedbyproliferationofimmaturewhitecellsandisthemostcommonmalignancyofchildhood.Acuteleukemiasaccountforthemajority(97%)ofcases.LeukemiaLeukemiaisadisease2LeukemiaTheleukemiasareclassifiedaccordingtothewhitebloodcelllineinvolved:

Acutelymphocyticleukemia(ALL)-----cellsoflymphoidlineage

Acutenon-lymphocyticleukemia(ANLL)-----cellsofgranulocyticormonocyticlineage.LeukemiaTheleukemiasar3Acutelymphocyticleukemia

ALLaccountfor80%ofchildhoodleukemiaandhasapeakinincidencebetweenage3and6years.Itisslightlymorecommoninboysthangirls.Acutelymphocyticleukemia

ALL4AcutelymphocyticleukemiaChildrenwithDownsyndrome,Fanconianemia,andataxiatelangiectasiaareatparticularriskofALL.Siblings,especiallytwins,ofchildrenwithleukemiaareapproximatelytwiceaslikelytohaveleukemiathanisthegeneralpopulation..AcutelymphocyticleukemiaChil5AcutelymphocyticleukemiaSomecasesofchildhoodALLmayrelatetohereditaryoracquiredmutationinthep53gene.Takenintotal,however,thesepredisposingcircumstancesorrelationshipsaccountforonlyasmallpropotionofcasesAcutelymphocyticleukemiaSome6ClinicalfeaturesInmostchildrenwithALL,thereisanacuteonsetofsymptomsandsignsarsingfrominfiltrationofthebonemarroworotherorganswithleukemicblastcells.Mostwillhaveoneormoreofthefollowing:ClinicalfeaturesInmostchild7Clinicalfeatures

“4Ps”

Pallor----anemia.Pyrexia----concomitantinfectionorthedeseaseitself.Purpura----thrombocytopeniaPain----Bonepain(pelvis,vertebralbodies,legs),duetoexpansionofmarrowcavity.

Abdominalpain,duetoliverandspleendistension.Clinicalfeatures

“4Ps”8ExpansionofmarrowcavityExpansionofmarrowcavity9ClinicalfeaturesasymtomaticlymphadenopathyandhepatosplenomegalytheCNS,testesandthekidneys----themostcommonlyaffectedextramedullarysites

Infection

----duetoneutropeniaClinicalfeaturesasymtomaticl10ClinicalfeatureHepatosplenomegalyreticuloendotheelialcellinfiltration.ClinicalfeatureHepatosplenome11白血病英文課件12Investigations

Peripheralbloodinvestigationsreveal:Anemia----normocytic,normochromic.Thombocytopenia.Neutropenia----totalWBCmaybelow,normal,orhigh.Blastcells.Investigations

Peripheralbloo13InvestigationsBonemarrowexaminationreveals:Replacementofnormalelementsbyleukemiccells.Adiagnosisofleukemiashouldalwaysbeconfirmedbybonemarrowaspiration.InvestigationsBonemarrowexam14MorphologiesandhistochemicalclassificationUnderlightmicroscope,thesystemdevelopedbyFABdivideslymphablastsinto3categories:L1:small,scantycytoplasmandinconspicuousnucleoli.(85%ofcases)L2:generallylarger,moreprominentnucleoliandabundantcytoplasm.L3

:large,deepcytoplasmicbasophilicandprominentcytoplasmicvacuolation,identicaltothecellsofBurkittlymphoma.(1-2%)Morphologiesandhistochemical15ALL-L1ALL-L2ALL-L3ALL-L1ALL-L2ALL-L316DifferentialdiagnosisInfectiousmononcleosisHistiocytosisXHypoplasticandaplasticanemiaJuvenilerheumatoidarthritisITP

DifferentialdiagnosisInfectio17TreatmentSurportivetherapySpecifictherapyPreventionofCNSLTreatmentofTLTransplantationofhemopoieticstemcellTreatmentSurportivetherapy18SpecifictreatmentInduction

(VDLP/CODPL)Consolidation(CAT/VM26+A)Prevetionofextramedullaryleukemia(HDMTX)Maintenance(6-MP+MTX)IntensifySpecifictreatmentInduction(V19SurportivetreatmentTreatmentofinfection.TransfusedbloodandplateletG-CSFandGM-CSFPrevetionoftumorlysissyndromeAlkalinizationofurineHydrationAllopurinolTheotherSurportivetreatmentTreatment20PrevetionofextramedullaryleukemiaintrathecalMTX,Ara-CandDXMHDMTX+CFPrevetionofextramedullaryle21TreatmentofCNSLintrathecalMTX,Ara-CandDXM(三聯(lián)鞘內注射法)HDMTX+CF(大劑量甲氨蝶呤-四氫葉酸鈣)cranialirradiation(顱腦放射治療）TreatmentofCNSLintrathecalM22Induction4weeksofcombinationchemotherapy:VDPL/CODPLDNR(柔紅霉素）L-asparaginase（左旋門冬酰氨）Vincristine(長春新堿）Prednisolone（潑尼松）CODPL

Induction4weeksofcombinatio23Maintenance

chemotherapycontinuesfor2yearsfromdiagnosis:6-MPor6-TG（硫鳥嘌呤）+MTXFormerinductiontherapyshouldbecarriedonPeriodicallyMaintenancechemotherapyconti24Consolidationcontinuedsystemictherapywithblocksof“intensification”therapyforselectedpatients.VM-26+Ara-c/VDP/VDPLCAM(T)CTX（甲氨蝶呤）Ara-c（阿糖胞苷）6MP（巰嘌呤)(6-TG)

Consolidationcontinuedsystemi25PrognosisThechildrencangetmuchbetterprognosisthanthetheadult.Their5-yearsurvivalrateis70-80%,whiletheircounterpartis20-30%.ANLL:5-yearsurvivalrateis40-50%PrognosisThechildrencanget26白血病細胞的遺傳學特征染色體數目50的超二倍體急淋細胞97%以上含有3~4條21號染色體，21號染色體上有編碼還原型四氫葉酸轉運蛋白的拷貝基因，這種轉運蛋白的高表達導致甲氨蝶呤的活性代謝產物多聚谷氨酰甲氨蝶呤在細胞內的高度累積，因此超二倍體急淋細胞對基于甲氨蝶呤的化療異常敏感，這類病人的預后非常好，5年EFS為75%~90%。白血病細胞的遺傳學特征染色體數目50的超二27白血病細胞的遺傳學特征美國COG組研究顯示4、10和17三體也是獨立的預后良好指標，這類病人7年EFS90%，機理尚不清楚。白血病細胞的遺傳學特征美國COG組研究顯示428白血病細胞的遺傳學特征t(12;21)(p13;q22)易位形成的融合基因TEL/AML1見于25%急淋患兒。研究表明這類白血病細胞對L-ASP高度敏感。stJude兒童研究醫(yī)院用含有L-ASP的強化療治療t(12;21)陽性的ALL患兒獲得較好效果。一般認為t(12;21)陽性患兒首次完全緩解期長且早期復發(fā)率低，但部分患兒晚期復發(fā)，復發(fā)后對化療依然敏感，易獲二次緩解。白血病細胞的遺傳學特征t(12;21)(p1329白血病細胞的遺傳學特征

t(1;19)(q23;q13)易位形成的E2A/PBX1融合基因多見于胞漿重鏈陽性的前B急淋。過去認為t(1;19)陽性急淋患兒發(fā)病時常伴有高白細胞數、高LDH及高CNS白血病發(fā)病率，預后不佳。但近年來強烈化療已使其成為兒童急淋中預后最良好型之一，這部分患兒的5年EFS接近90%。白血病細胞的遺傳學特征t(1;19)(q2330白血病細胞的遺傳學特征位于11q23的MLL基因可與30多種基因發(fā)生易位，統(tǒng)稱MLL基因重排，見于6%的急淋患兒，其中最常見的為t(4;11)(q21;q23)易位形成的融合基因MLL/AF4，絕大多數嬰兒白血病表達該融合基因。最近一個大宗病例統(tǒng)計顯示任何MLL基因重排的ALL患兒預后都不好，長期EFS只有20%~25%，尤其MLL基因重排的嬰兒比1歲以上患兒預后更差。t(4;11)陽性嬰兒白血病細胞對阿糖胞苷相對敏感。白血病細胞的遺傳學特征位于11q23的MLL31白血病細胞的遺傳學特征

t(9;22)(q34;q11)易位形成的融合基因BCR/ABL見于3%~5%的兒童急淋，為預后最差的一類，尤其初診白細胞≥50109/L、發(fā)病年齡≥10歲或強的松反應不良的患兒建議第一次緩解后即行異基因造血干細胞移植，以減少復發(fā)，提高總體生存率。

白血病細胞的遺傳學特征t(9;22)(q332THECHILDHOODLEUKEMIA

THECHILDHOODLEUKEMIA33LeukemiaLeukemiaisadiseasecharacterizedbyproliferationofimmaturewhitecellsandisthemostcommonmalignancyofchildhood.Acuteleukemiasaccountforthemajority(97%)ofcases.LeukemiaLeukemiaisadisease34LeukemiaTheleukemiasareclassifiedaccordingtothewhitebloodcelllineinvolved:

Acutelymphocyticleukemia(ALL)-----cellsoflymphoidlineage

Acutenon-lymphocyticleukemia(ANLL)-----cellsofgranulocyticormonocyticlineage.LeukemiaTheleukemiasar35Acutelymphocyticleukemia

ALLaccountfor80%ofchildhoodleukemiaandhasapeakinincidencebetweenage3and6years.Itisslightlymorecommoninboysthangirls.Acutelymphocyticleukemia

ALL36AcutelymphocyticleukemiaChildrenwithDownsyndrome,Fanconianemia,andataxiatelangiectasiaareatparticularriskofALL.Siblings,especiallytwins,ofchildrenwithleukemiaareapproximatelytwiceaslikelytohaveleukemiathanisthegeneralpopulation..AcutelymphocyticleukemiaChil37AcutelymphocyticleukemiaSomecasesofchildhoodALLmayrelatetohereditaryoracquiredmutationinthep53gene.Takenintotal,however,thesepredisposingcircumstancesorrelationshipsaccountforonlyasmallpropotionofcasesAcutelymphocyticleukemiaSome38ClinicalfeaturesInmostchildrenwithALL,thereisanacuteonsetofsymptomsandsignsarsingfrominfiltrationofthebonemarroworotherorganswithleukemicblastcells.Mostwillhaveoneormoreofthefollowing:ClinicalfeaturesInmostchild39Clinicalfeatures

“4Ps”

Pallor----anemia.Pyrexia----concomitantinfectionorthedeseaseitself.Purpura----thrombocytopeniaPain----Bonepain(pelvis,vertebralbodies,legs),duetoexpansionofmarrowcavity.

Abdominalpain,duetoliverandspleendistension.Clinicalfeatures

“4Ps”40ExpansionofmarrowcavityExpansionofmarrowcavity41ClinicalfeaturesasymtomaticlymphadenopathyandhepatosplenomegalytheCNS,testesandthekidneys----themostcommonlyaffectedextramedullarysites

Infection

----duetoneutropeniaClinicalfeaturesasymtomaticl42ClinicalfeatureHepatosplenomegalyreticuloendotheelialcellinfiltration.ClinicalfeatureHepatosplenome43白血病英文課件44Investigations

Peripheralbloodinvestigationsreveal:Anemia----normocytic,normochromic.Thombocytopenia.Neutropenia----totalWBCmaybelow,normal,orhigh.Blastcells.Investigations

Peripheralbloo45InvestigationsBonemarrowexaminationreveals:Replacementofnormalelementsbyleukemiccells.Adiagnosisofleukemiashouldalwaysbeconfirmedbybonemarrowaspiration.InvestigationsBonemarrowexam46MorphologiesandhistochemicalclassificationUnderlightmicroscope,thesystemdevelopedbyFABdivideslymphablastsinto3categories:L1:small,scantycytoplasmandinconspicuousnucleoli.(85%ofcases)L2:generallylarger,moreprominentnucleoliandabundantcytoplasm.L3

:large,deepcytoplasmicbasophilicandprominentcytoplasmicvacuolation,identicaltothecellsofBurkittlymphoma.(1-2%)Morphologiesandhistochemical47ALL-L1ALL-L2ALL-L3ALL-L1ALL-L2ALL-L348DifferentialdiagnosisInfectiousmononcleosisHistiocytosisXHypoplasticandaplasticanemiaJuvenilerheumatoidarthritisITP

DifferentialdiagnosisInfectio49TreatmentSurportivetherapySpecifictherapyPreventionofCNSLTreatmentofTLTransplantationofhemopoieticstemcellTreatmentSurportivetherapy50SpecifictreatmentInduction

(VDLP/CODPL)Consolidation(CAT/VM26+A)Prevetionofextramedullaryleukemia(HDMTX)Maintenance(6-MP+MTX)IntensifySpecifictreatmentInduction(V51SurportivetreatmentTreatmentofinfection.TransfusedbloodandplateletG-CSFandGM-CSFPrevetionoftumorlysissyndromeAlkalinizationofurineHydrationAllopurinolTheotherSurportivetreatmentTreatment52PrevetionofextramedullaryleukemiaintrathecalMTX,Ara-CandDXMHDMTX+CFPrevetionofextramedullaryle53TreatmentofCNSLintrathecalMTX,Ara-CandDXM(三聯(lián)鞘內注射法)HDMTX+CF(大劑量甲氨蝶呤-四氫葉酸鈣)cranialirradiation(顱腦放射治療）TreatmentofCNSLintrathecalM54Induction4weeksofcombinationchemotherapy:VDPL/CODPLDNR(柔紅霉素）L-asparaginase（左旋門冬酰氨）Vincristine(長春新堿）Prednisolone（潑尼松）CODPL

Induction4weeksofcombinatio55Maintenance

chemotherapycontinuesfor2yearsfromdiagnosis:6-MPor6-TG（硫鳥嘌呤）+MTXFormerinductiontherapyshouldbecarriedonPeriodicallyMaintenancechemotherapyconti56Consolidationcontinuedsystemictherapywithblocksof“intensification”therapyforselectedpatients.VM-26+Ara-c/VDP/VDPLCAM(T)CTX（甲氨蝶呤）Ara-c（阿糖胞苷）6MP（巰嘌呤)(6-TG)

Consolidationcontinuedsystemi57PrognosisThechildrencangetmuchbetterprognosisthanthetheadult.Their5-yearsurvivalrateis70-80%,whiletheircounterpartis20-30%.ANLL:5-yearsurvivalrateis40-50%PrognosisThechildrencanget58白血病細胞的遺傳學特征染色體數目50的超