白血病英文课件.ppt

1、THE CHILDHOOD LEUKEMIA LeukemiaLeukemia is a disease c h a r a c t e r i z e d b y proliferation of immature white cells and is the most common malignancy of childhood.Acute leukemias account for the majority(97%)of cases.Leukemia The leukemias are classified according to the white blood cell line i

2、nvolved:Acute lymphocytic leukemia(ALL)-cells of lymphoid lineage A c u t e n o n-l y m p h o c y t i c leukemia(ANLL)-cells of granulocytic or monocytic lineage.Acute lymphocytic leukemiaALL account for 80%of childhood leukemia and has a peak in incidence between age 3 and 6 years.It is slightly mo

3、re common in boys than girls.Acute lymphocytic leukemiaChildren with Down syndrome,Fanconi anemia,and ataxiatelangiectasia are at particular risk of ALL.Siblings,especially twins,of children with leukemia are approximately twice as likely to have leukemia than is the general population.Acute lymphoc

4、ytic leukemiaSome cases of childhood ALL may relate to hereditary or acquired mutation in the p53 gene.Taken in total,however,these predisposing circumstances or relationships account for only a small propotion of casesClinical featuresIn most children with ALL,there is an acute onset of symptoms an

5、d signs arsing from infiltration of the bone marrow or other organs with leukemic blast cells.Most will have one or more of the following:Clinical features“4 Ps”Pallor-anemia.Pyrexia-concomitant infection or the desease itself.Purpura-thrombocytopeniaPain-Bone pain(pelvis,vertebral bodies,legs),due

6、to expansion of marrow cavity.Abdominal pain,due to liver and spleen distension.Expansion of marrow cavityClinical featuresasymtomatic lymphadenopathy and hepatosplenomegaly the CNS,testes and the kidneys-the most commonly affected extramedullary sites Infection-due to neutropeniaClinical featureHep

7、atosplenomegaly reticuloendotheelial cell infiltration.InvestigationsPeripheral blood investigations reveal:Anemia-normocytic,normochromic.Thombocytopenia.Neutropenia-total WBC may be low,normal,or high.Blast cells.InvestigationsBone marrow examination reveals:Replacement of normal elements by leuke

8、mic cells.A diagnosis of leukemia should always be confirmed by bone marrow aspiration.Morphologies and histochemical classificationUnder light microscope,the system developed by FAB divides lymphablasts into 3 categories:L1:small,scanty cytoplasm and inconspicuous nucleoli.(85%of cases)L2:generally

9、 larger,more prominent nucleoli and abundant cytoplasm.L3:large,deep cytoplasmic basophilic and prominent cytoplasmic vacuolation,identical to the cells of Burkitt lymphoma.(1-2%)ALL-L1ALL-L2ALL-L3Differential diagnosisInfectious mononcleosisHistiocytosis XHypoplastic and aplastic anemiaJuvenile rhe

10、umatoid arthritisITP TreatmentSurportive therapySpecific therapyPrevention of CNSLTreatment of TLTransplantation of hemopoietic stem cellSpecific treatmentInduction(VDLP/CODPL)Consolidation(CAT/VM26+A)Prevetion of extramedullary leukemia(HDMTX)Maintenance(6-MP+MTX)IntensifySurportive treatmentTreatm

11、ent of infection.Transfused blood and plateletG-CSF and GM-CSFPrevetion of tumor lysis syndromeAlkalinization of urineHydrationAllopurinolThe otherPrevetion of extramedullary leukemiaintrathecal MTX,Ara-C and DXMHDMTX+CFTreatment of CNSLintrathecal MTX,Ara-C and DXM(三联鞘内注射法)HDMTX+CF(大剂量甲氨蝶呤-四氢叶酸钙)cr

12、anial irradiation(颅脑放射治疗）Induction4 weeks of combination chemotherapy:VDPL/CODPLDNR(柔红霉素）柔红霉素）L-asparaginase（左旋门冬酰氨）左旋门冬酰氨）Vincristine(长春新碱）长春新碱）Prednisolone（泼尼松）泼尼松）CODPLMaintenance chemotherapy continues for 2 years from diagnosis:6-MP or 6-TG（硫鸟嘌呤）硫鸟嘌呤）+MTXFormer induction therapy should be carri

13、ed on Periodically Consolidationcontinued systemic therapy with blocks of“intensification”therapy for selected patients.VM-26+Ara-c/VDP/VDPLCAM(T)CTX（甲氨蝶呤）甲氨蝶呤）Ara-c（阿糖胞苷）阿糖胞苷）6MP（巯嘌呤巯嘌呤)(6-TG)PrognosisThe children can get much better prognosis than the the adult.Their 5-year survival rate is 70-80%

14、,while their counterpart is 20-30%.ANLL:5-year survival rate is 40-50%染色体数目 50的超二倍体急淋细胞97%以上含有34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%。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EFS 90%，机理尚不清楚。t(12;21)(p13;q22)易位形成的融合基因

15、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。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%。位于11q

16、23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。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。