Leukemia (白血病).ppt

1、2020/10/8,xie Yi,Hua Shan Hospital,1,Leukemia (白血病),谢毅（Xie yi） Dep.Hematology，Huashan Hospital,2020/10/8,xie Yi,Hua Shan Hospital,2,Concept of leukemia,Definition It is the results of the tumor proliferation of heamotopoietic stem cells.（造血干细胞） Leukemia is a malignant blood disorder. (not solid tumo

2、r),2020/10/8,xie Yi,Hua Shan Hospital,3,Heamatopoietic stem cell,reproduction HSC lymphoid HSC HSC differentiation early progenitor CFU-GEMM myeloid HSC Heamatopoietic Stem Cell (HSC) is the primary cell of Heamatopoietic system and immune system.,2020/10/8,xie Yi,Hua Shan Hospital,5,Tumor prolifera

3、tion of HSC,Differentiation of HSC is blocked. Leukemia cells are stopped on a differentiation stage of HSC 21)(q22;q22),(AML1/ETO) AML with t(15;17)(q22;q12),(PML/RAR) AML with inv(16)(p13;q22) or t(16;16)(p13;q22) ,CBF/MYH11 AML with 11q23 (MLL) abnormalities,2020/10/8,xie Yi,Hua Shan Hospital,10,

4、WHO classification (2001),(2), AML with multilineage dysplasia With prior myelodysplastic syndrome Without prior myelodysplastic syndrome (3),AML and myelodysplastic syndrome, therapy related Alkylating agent related Topoisomerase ll inhibitor-related,2020/10/8,xie Yi,Hua Shan Hospital,11,WHO classi

5、fication (2001),(4) AML not otherwise categorized AML minimally differentiation AML without maturation AML with maturation Acute myelomonocytic leukemia Acute monoblastic and monocytic leukemia Acute erythroid leukemia Acute megakaryoblastic leukemia Acute basophilic leukemia Acute panmyelosis with

6、myelofibrosis Myeloid sarcoma (5) Acute leukemia of ambiguous lineage,2020/10/8,xie Yi,Hua Shan Hospital,12,WHO classification (2001),2, chronic myeloid leukemia (1), chronic myeloproliferative disease chronic myelogenous leukemia Chronic neutrophilic leukemia Chronic eosinophilic leukemia/hypereosi

7、nophilic syndrome (2), myelodysplastic/myeloproliferative disease Chronic myelomonocytic leukemia Atypical chronic myeloid leukemia Juvenile myelomonocytic leukemia,2020/10/8,xie Yi,Hua Shan Hospital,13,WHO classification (2001),3, B-cell neoplasms (1), Precursor B-cell neoplasm Precursor B lymphobl

8、astic leukemia (2), Mature B-cell neoplasm Chronic lymphocytic leukemia/Small lymphocytic lymphoma (CLL/SLL) B-cell prolymphocytic leukemia Hairy cell leukemia Burkitt lymphoma/leukemia,2020/10/8,xie Yi,Hua Shan Hospital,14,WHO classification (2001),4, T-cell and NK-cell neoplasms (1), Precursor T-c

9、ell neoplasm Precursor T lymphoblastic leukemia (2), Mature T-cell and NK-cell neoplasms T-cell prolymphocytic leukemia T-cell large granular lymphocytic leukemia Aggressive NK leukemia/lymphoma Adult T-cell leukemia/lymphoma,2020/10/8,xie Yi,Hua Shan Hospital,15,Epidemiology : incidence,3/105 ， inc

10、rease with years? acutechronic , AMLALL Special distribution: Sex man：female2：1 Age ALL, adolescent 8020y; AML, adult CML, 2050 years old; CLL ,5070 years old Area adult T lymphocytic leukemia CML, eastern countries CLL, western countries,2020/10/8,xie Yi,Hua Shan Hospital,16,Epidemiology: mortality

11、,2.51/105 Area city the countryside ChinaSingaporeJapanUSAunited Kingdom Sweden(7.59/105) In order of the mortality of malignant tumors in114y，leukemia is most high in1544y，leukemia is third high(stomach Ca liver Ca) in all person, leukemia is sixth or eighth high,2020/10/8,xie Yi,Hua Shan Hospital,

12、17,Etiology,radiation 1、atom bomb （长 崎）1Km 1.5km 2km 100 22 2.6 2、high dose X radiation、32P therapy,2020/10/8,xie Yi,Hua Shan Hospital,18,Etiology,chemicals benzene Therapy-related leukemia 47/440000,2020/10/8,xie Yi,Hua Shan Hospital,19,virus ATLV ，1981，Japan(鹿儿岛) electric microscope：virus C The se

13、rum antibody titer of ATLV decrease with the distance from 鹿儿岛,Etiology,2020/10/8,xie Yi,Hua Shan Hospital,20,Genetics twin(same egg ) 0.20.25 sibling 10/105 Downs syndrome (21+) 4060/105 Fanconi anemia 4/66,Etiology,2020/10/8,xie Yi,Hua Shan Hospital,21,from other blood disorders Myeloproliferative

14、 Disease chronic myeloid leukemia(CML) polycythemia vera(PV) primary thrombocythemia(PT) myelofibrosis(MF) myelodysplastic syndrome(MDS) paroxysmal nocturnal hemoglobinuria(PNH) lymphoma or myeloma,Etiology,2020/10/8,xie Yi,Hua Shan Hospital,22,Mechanism,Radiation, chemicals, virus, genetics 21) t(6

15、;9) M3 t(15;17) M4 inv(16) M5 t(4;11), t(8;16) M6 M7,ALL t(9;22) (B) t(8;14),2020/10/8,xie Yi,Hua Shan Hospital,34,Fusion gene molecular,AML1/ETO PML/RAR CBF/MYH11 MLL abnormalites BCR/ABL,2020/10/8,xie Yi,Hua Shan Hospital,35,MICM TYPING DIAGNOSIS,We could use traditional typing diagnosis as what F

16、AB asked. If the situation permit, we could use FCM, chromosome, PCR or FISH in a WHO typing diagnosis way.,2020/10/8,xie Yi,Hua Shan Hospital,36,Differential Diagnosis,Myelodysplastic syndrome (MDS) refractory anemia or pancytopenia, BM: dysplasia, blasts30% Leukemoid reaction mature leukocytes pro

17、liferative would play a main role, NAP, if progenitor increase, only shortly on time CML: mature progenitors E、B， NAP=0, ph()，bcr-abl(+) Stomatitis，Infectious mononucleosis，ITP, AA，agranulocytopenia There is no blasts in bone marrow,principle: early，combine，full，interval，by stages,why early ? The ov

18、er hyperplasia sternal tenderness WBC 101000109/L Granulocytes at all stages of development are present in blood, NAP0 BM proliferate ,Granulopoiesis is dominent blast10%， B & E and Erythropoiesis megakaryocytopeoiesis and reticulin fibrosis ph1(+) ,bcr-abl (+),CML by stages,Chronic phase accelerati

19、ve phas blast phase Asymptomatic, anemia,hemorrhage, like as acute splenomegaly splenomegaly leukemia eosinophilia basophilic cell basophlia 20% blast blast blast 20% PLT 1000109/L,2020/10/8,xie Yi,Hua Shan Hospital,71,CML:differentiation diagnosis,1、leukemoid reaction： infection,cancer etc WBC ,the

20、re isnt splenomegaly NAP ，absence of Blast, ph1, bcrabl 2、myelofibrosis： WBC biopsy：collagen fibrosis,2020/10/8,xie Yi,Hua Shan Hospital,72,CML:differentiation diagnosis,3、acute leukemia ph1 in 2% AML ph1 in 525% ALL 4、acute abdomen Absence of splenomegaly and the fricative in left hypochondrial reg

21、ion,2020/10/8,xie Yi,Hua Shan Hospital,73,CML : treatment,1, keep WBC 4.010.0109/L (1) Hydroxyurea (羟基脲) 0.52.0 tid Busulfan (马利兰)110mg qd 当归芦荟丸青黛靛玉红甲异靛 (2)Interferon -2b 500万u H qd Ara-C 25mg H qd 1421天 (3) Grivec (Greevec,格列卫 ,STI 571 ) 400600mg/d,2020/10/8,xie Yi,Hua Shan Hospital,74,CMLs THERAPY

22、,2, WBC200109/L, Leukostasis therapeutic luekopheresis 3, Blast Phase Like as acute leukemia , difficultly 4, Allo-BMT, Allo- PBSCT, CBT) curabale,2020/10/8,xie Yi,Hua Shan Hospital,75,Chronic lymphocytic leukemia(CLL),CLL is neoplastic disease The apoptosis of lymphocyte is inhibited Accumulation o

23、f small mature appearing CD5+ B lymphocytes in blood ，marrow and lymphoid tissues immunodeficiency incidence 20/ 105 in western country, 2/ 105 in China 90%50y male :female=2:1,2020/10/8,xie Yi,Hua Shan Hospital,76,CLL:diagnosis,25% patients are asymptomatic Maybe nontender lymphadenopathy, splenome

24、galy and hepatomegaly Unexplained absolute lymphcytosis WBC 10200, lymphocytes 50%， 5109/L (5000/mm3 ) , 4 weeks BM lymphocytes 40%,2020/10/8,xie Yi,Hua Shan Hospital,77,CLL:diagnosis,Lymphocyte surface immunologic marker can determine monoclonality immunophenotyping B，surface or cytoplasmic immunoglobuline ， or light chains ，CD