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1、THE CHILDHOOD LEUKEMIA,站,Leukemia,Leukemia is a disease characterized by 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 involve
2、d: Acute lymphocytic leukemia (ALL) - cells of lymphoid lineage Acute non-lymphocytic leukemia (ANLL) - cells of granulocytic or monocytic lineage.,Acute lymphocytic leukemia,ALL account for 80% of childhood leukemia and has a peak in incidence between age 3 and 6 years. It is slightly more common i
3、n boys than girls.,Acute lymphocytic leukemia,Children 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 lympho
4、cytic leukemia,Some 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 cases,Clinical features,In most children with ALL , there is an acute onset of
5、symptoms and 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 - thrombocytopenia Pain - Bone pain (pelvi
6、s , vertebral bodies , legs ), due to expansion of marrow cavity . Abdominal pain , due to liver and spleen distension .,Expansion of marrow cavity,Clinical features,asymtomatic lymphadenopathy and hepatosplenomegaly the CNS , testes and the kidneys - the most commonly affected extramedullary sites
7、Infection - due to neutropenia,Clinical feature,Hepatosplenomegaly reticuloendotheelial cell infiltration.,Investigations,Peripheral blood investigations reveal : Anemia - normocytic , normochromic . Thombocytopenia . Neutropenia - total WBC may be low , normal , or high. Blast cells .,Investigation
8、s,Bone marrow examination reveals : Replacement of normal elements by leukemic cells. A diagnosis of leukemia should always be confirmed by bone marrow aspiration.,Morphologies and histochemical classification,Under light microscope , the system developed by FAB divides lymphablasts into 3 categorie
9、s: L1 : small ,scanty cytoplasm and inconspicuous nucleoli .(85% of cases ) L2 : generally 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-L1,ALL-L2,ALL-L3
10、,Differential diagnosis,Infectious mononcleosis Histiocytosis X Hypoplastic and aplastic anemia Juvenile rheumatoid arthritis ITP,站,Treatment,Surportive therapy Specific therapy Prevention of CNSL Treatment of TL Transplantation of hemopoietic stem cell,Specific treatment,Induction (VDLP/CODPL) Cons
11、olidation(CAT/VM26+A) Prevetion of extramedullary leukemia(HDMTX) Maintenance(6-MP+MTX) Intensify,Surportive treatment,Treatment of infection. Transfused blood and platelet G-CSF and GM-CSF Prevetion of tumor lysis syndrome Alkalinization of urine Hydration Allopurinol The other,Prevetion of extrame
12、dullary leukemia,intrathecal MTX, Ara-C and DXM HDMTX+CF,Treatment of CNSL,intrathecal 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) cranial irradiation(颅脑放射治疗）,Induction,4 weeks of combination chemotherapy: VDPL/CODPL DNR (柔红霉素） L-asparaginase（左旋门冬酰氨） Vincristine (长春新碱） Prednisolone（泼尼松） CODP
13、L,Maintenance,chemotherapy continues for 2 years from diagnosis : 6-MP or 6-TG（硫鸟嘌呤）+ MTX Former induction therapy should be carried on Periodically,Consolidation,continued systemic therapy with blocks of “intensification” therapy for selected patients. VM-26+Ara-c/VDP/VDPL CAM(T) CTX（甲氨蝶呤） Ara-c（阿糖
14、胞苷） 6MP（巯嘌呤)(6-TG),Prognosis,The children can get much better prognosis than the the adult. Their 5-year survival rate is 70-80%, while their counterpart is 20-30%. ANLL: 5-year survival rate is 40-50%,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
15、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,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。,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。st Jude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
16、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(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,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,t(9;22) (q34;q11)易位形成的融合基因BCR/ABL 见于3%5%的儿童急
