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(nèi)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(mén)冬酰氨）Vincristine(長(zhǎng)春新堿）Prednisolone（潑尼松）CODPL

Induction4weeksofcombinatio23Maintenance

chemotherapycontinuesfor2yearsfromdiagnosis:6-MPor6-TG（硫鳥(niǎo)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(xì)胞的遺傳學(xué)特征染色體數(shù)目50的超二倍體急淋細(xì)胞97%以上含有3~4條21號(hào)染色體，21號(hào)染色體上有編碼還原型四氫葉酸轉(zhuǎn)運(yùn)蛋白的拷貝基因，這種轉(zhuǎn)運(yùn)蛋白的高表達(dá)導(dǎo)致甲氨蝶呤的活性代謝產(chǎn)物多聚谷氨酰甲氨蝶呤在細(xì)胞內(nèi)的高度累積，因此超二倍體急淋細(xì)胞對(duì)基于甲氨蝶呤的化療異常敏感，這類(lèi)病人的預(yù)后非常好，5年EFS為75%~90%。白血病細(xì)胞的遺傳學(xué)特征染色體數(shù)目50的超二27白血病細(xì)胞的遺傳學(xué)特征美國(guó)COG組研究顯示4、10和17三體也是獨(dú)立的預(yù)后良好指標(biāo)，這類(lèi)病人7年EFS90%，機(jī)理尚不清楚。白血病細(xì)胞的遺傳學(xué)特征美國(guó)COG組研究顯示428白血病細(xì)胞的遺傳學(xué)特征t(12;21)(p13;q22)易位形成的融合基因TEL/AML1見(jiàn)于25%急淋患兒。研究表明這類(lèi)白血病細(xì)胞對(duì)L-ASP高度敏感。stJude兒童研究醫(yī)院用含有L-ASP的強(qiáng)化療治療t(12;21)陽(yáng)性的ALL患兒獲得較好效果。一般認(rèn)為t(12;21)陽(yáng)性患兒首次完全緩解期長(zhǎng)且早期復(fù)發(fā)率低，但部分患兒晚期復(fù)發(fā)，復(fù)發(fā)后對(duì)化療依然敏感，易獲二次緩解。白血病細(xì)胞的遺傳學(xué)特征t(12;21)(p1329白血病細(xì)胞的遺傳學(xué)特征

t(1;19)(q23;q13)易位形成的E2A/PBX1融合基因多見(jiàn)于胞漿重鏈陽(yáng)性的前B急淋。過(guò)去認(rèn)為t(1;19)陽(yáng)性急淋患兒發(fā)病時(shí)常伴有高白細(xì)胞數(shù)、高LDH及高CNS白血病發(fā)病率，預(yù)后不佳。但近年來(lái)強(qiáng)烈化療已使其成為兒童急淋中預(yù)后最良好型之一，這部分患兒的5年EFS接近90%。白血病細(xì)胞的遺傳學(xué)特征t(1;19)(q2330白血病細(xì)胞的遺傳學(xué)特征位于11q23的MLL基因可與30多種基因發(fā)生易位，統(tǒng)稱(chēng)MLL基因重排，見(jiàn)于6%的急淋患兒，其中最常見(jiàn)的為t(4;11)(q21;q23)易位形成的融合基因MLL/AF4，絕大多數(shù)嬰兒白血病表達(dá)該融合基因。最近一個(gè)大宗病例統(tǒng)計(jì)顯示任何MLL基因重排的ALL患兒預(yù)后都不好，長(zhǎng)期EFS只有20%~25%，尤其MLL基因重排的嬰兒比1歲以上患兒預(yù)后更差。t(4;11)陽(yáng)性嬰兒白血病細(xì)胞對(duì)阿糖胞苷相對(duì)敏感。白血病細(xì)胞的遺傳學(xué)特征位于11q23的MLL31白血病細(xì)胞的遺傳學(xué)特征

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

白血病細(xì)胞的遺傳學(xué)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(nèi)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(mén)冬酰氨）Vincristine(長(zhǎng)春新堿）Prednisolone（潑尼松）CODPL

Induction4weeksofcombinatio55Maintenance

chemotherapycontinuesfor2yearsfromdiagnosis:6-MPor6-TG（硫鳥(niǎo)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(xì)胞的遺傳學(xué)特征染色體數(shù)目50的超