白血病英文课件

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白血病英文课件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(三联鞘内注射法)HDMTX+CF(大剂量甲氨蝶呤-四氢叶酸钙)cranialirradiation(颅脑放射治疗）TreatmentofCNSLintrathecalM22Induction4weeksofcombinationchemotherapy:VDPL/CODPLDNR(柔红霉素）L-asparaginase（左旋门冬酰氨）Vincristine(长春新碱）Prednisolone（泼尼松）CODPL

Induction4weeksofcombinatio23Maintenance

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

Consolidationcontinuedsystemi25PrognosisThechildrencangetmuchbetterprognosisthanthetheadult.Their5-yearsurvivalrateis70-80%,whiletheircounterpartis20-30%.ANLL:5-yearsurvivalrateis40-50%PrognosisThechildrencanget26白血病细胞的遗传学特征染色体数目50的超二倍体急淋细胞97%以上含有3~4条21号染色体，21号染色体上有编码还原型四氢叶酸转运蛋白的拷贝基因，这种转运蛋白的高表达导致甲氨蝶呤的活性代谢产物多聚谷氨酰甲氨蝶呤在细胞内的高度累积，因此超二倍体急淋细胞对基于甲氨蝶呤的化疗异常敏感，这类病人的预后非常好，5年EFS为75%~90%。白血病细胞的遗传学特征染色体数目50的超二27白血病细胞的遗传学特征美国COG组研究显示4、10和17三体也是独立的预后良好指标，这类病人7年EFS90%，机理尚不清楚。白血病细胞的遗传学特征美国COG组研究显示428白血病细胞的遗传学特征t(12;21)(p13;q22)易位形成的融合基因TEL/AML1见于25%急淋患儿。研究表明这类白血病细胞对L-ASP高度敏感。stJude儿童研究医院用含有L-ASP的强化疗治疗t(12;21)阳性的ALL患儿获得较好效果。一般认为t(12;21)阳性患儿首次完全缓解期长且早期复发率低，但部分患儿晚期复发，复发后对化疗依然敏感，易获二次缓解。白血病细胞的遗传学特征t(12;21)(p1329白血病细胞的遗传学特征

t(1;19)(q23;q13)易位形成的E2A/PBX1融合基因多见于胞浆重链阳性的前B急淋。过去认为t(1;19)阳性急淋患儿发病时常伴有高白细胞数、高LDH及高CNS白血病发病率，预后不佳。但近年来强烈化疗已使其成为儿童急淋中预后最良好型之一，这部分患儿的5年EFS接近90%。白血病细胞的遗传学特征t(1;19)(q2330白血病细胞的遗传学特征位于11q23的MLL基因可与30多种基因发生易位，统称MLL基因重排，见于6%的急淋患儿，其中最常见的为t(4;11)(q21;q23)易位形成的融合基因MLL/AF4，绝大多数婴儿白血病表达该融合基因。最近一个大宗病例统计显示任何MLL基因重排的ALL患儿预后都不好，长期EFS只有20%~25%，尤其MLL基因重排的婴儿比1岁以上患儿预后更差。t(4;11)阳性婴儿白血病细胞对阿糖胞苷相对敏感。白血病细胞的遗传学特征位于11q23的MLL31白血病细胞的遗传学特征

t(9;22)(q34;q11)易位形成的融合基因BCR/ABL见于3%~5%的儿童急淋，为预后最差的一类，尤其初诊白细胞≥50109/L、发病年龄≥10岁或强的松反应不良的患儿建议第一次缓解后即行异基因造血干细胞移植，以减少复发，提高总体生存率。

白血病细胞的遗传学特征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白血病英文课件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(三联鞘内注射法)HDMTX+CF(大剂量甲氨蝶呤-四氢叶酸钙)cranialirradiation(颅脑放射治疗）TreatmentofCNSLintrathecalM54Induction4weeksofcombinationchemotherapy:VDPL/CODPLDNR(柔红霉素）L-asparaginase（左旋门冬酰氨）Vincristine(长春新碱）Prednisolone（泼尼松）CODPL

Induction4weeksofcombinatio55Maintenance

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

Consolidationcontinuedsystemi57PrognosisThechildrencangetmuchbetterprognosisthanthetheadult.Their5-yearsurvivalrateis70-80%,whiletheircounterpartis20-30%.ANLL:5-yearsurvivalrateis40-50%PrognosisThechildrencanget58白血病细胞的遗传学特征染色体数目50的超