白血病ppt课件

Leukemia （白血病）,陈方平,Leukemia,Therapy and Prognonis,Contents,Outline,Classification,Clinical features,Diagnosis,Acute leukema,Chronic leukema,,What Is Leukemia?,Cancer of the white blood cells Acute or Chronic Affects ability to produce normal blood cells Bone marrow makes abnormally large number of immature white blood cells called blasts,Definition,Abnormality of WBC,Marrow failure,Infiltration of tissues,Hematopoietic stem cell malignancies,Malignant proliferation of leukemic cells,Development of Leukemia in the Bloodstream,Legend,White Cell,Red Cell,Platelet,Blast,Germ,Sources from Leukemia, by D. Newton and D. Siegel,History,Means “white blood” in Greek Discovered by Dr. Alfred Velpeau in France, 1827 Named by pathologist Rudolf Virchow in Germany, 1845,Results in China（N/100,000）,Morbility in adults,2.0,1.0,ANLL,ALL,CML,CLL,1.62,0.69,0.36,0.05,Morbility,Etiology,Virus Radiation Chemicals Inheritance Other kinds of hematopoietic disease,Classification of leukemia,Acute,Chronic,Myeloid origin,Lymphoid origin,Acute Myeloid Leukemia (AML),Acute Lymphoblastic Leukemia (ALL),Chronic Myeloid Leukemia (CML),Chronic Lymphocytic Leukemia (CLL),Hematopoietic Stem Cell,Years,Months,Weeks, Days,Lifespan,Decades,Years,Months,Weeks, Days,Red blood cells,White blood cells,Platelets,Hematopoietic Stem Cell,Red blood cells,White blood cells,Platelets,Hematopoietic Stem Cell,Red blood cells,White blood cells,Platelets,Hematopoietic Stem Cell,Acute Leukemia,Hematopoietic Stem Cell,Hematopoietic Stem Cell,Chemotherapy,Hematopoietic Stem Cell,Remission,differentiation block,enhanced proliferation,Acute Leukemia,+,Gain of function mutations of tyrosine kinases eg. FLT3, c-KIT mutations N- and K-RAS mutations BCR-ABL TEL-PDGFbR,Loss of function of transcription factors needed for differentiation eg. AML1-ETO CBFb-SMMHC PML-RARa,Two-hit model of leukemogenesis,Classification of acute leukemia,ALL mainly children M F curable in 70% of children curable in minority of adults,AML mainly adults M F curable in minority of adults,Clinical features (一),Malignant proliferation of leukemic cells,Marrow failure,Infiltration of tissues,Anemia,Fever,Bleeding,Acute leukemia,Clinical features (二),Acute leukemia,Anemia (progressive, weakness, pale) Fever (mostly by infection) Common Severe Uncontrolled Pathogen：G-、G+、virus、fungus et.al,Clinical features (三),Acute leukemia,Bleeding Common、progressive locus：skin and mucous （purpura、ecchymosis ） Bleeding of internal organs,petechia,ecchymosis,purpura,Clinical features (三),Acute leukemia,Infiltration of tissues/organs Lymph node, enlargement of liver and spleen Bone pain CNSL（中枢神经系统白血病） Mouth、 skin 、eye（Granulocytic sarcoma ） Other（testis）,Infiltration of tissues (gum),Infiltration of tissues (skin),lymphadenopathy,Splenomegaly,Laboratory (一),Blood test WBC+DC：Hyperleukocytic AL(100109/L ) Hypoplastic AL (lower than normal) Blastic cell and juvenile cells HB+RBC Pt,Acute leukemia,Pictures Of Blood,Marrow blastic cells30% normal blood cells reduced hypoplastic leukemia Auer rods,数的异常,质的异常,Acute leukemia,Laboratory (二),Site for marrow samples,Marrow Biopsy:,Normal,AML,ALL,Auer rods,,Classification of acute leukemia,Methods 1.FAB 2.MICM,,Subclassification,ALL Common type( pre-B) B-cell T-cell Undifferentiated,,ALL L1 (85%): smaller, high n/c ratio, indistinct nucleoli,,ALL L2 (14%): larger, more cytoplasm, pleomorphic, more distinct nucleoli,,ALL L3 (1%): cytoplasmic basophilia (Ig), vacuoles (Burkitts leukemia),,Myelomono,FAB of AML,,形态学 Morphology 免疫学 Immunology 细胞遗传学 Cytogenetics 分子生物学 Molecular biology,MICM,Classification of acute leukemia,,MPO (right) & Sudan black (left) showing intense localised positivity in blasts,Laboratory（三）,Chemical dye L(淋) M（粒） N（单）,POX - + -+ NSE - -+ + NaF - + PAS + -+ +,Acute leukemia,Acute leukemia,Laboratory(四),Immunology ANLLCD13、CD33、CD14 T-ALLCD3、CD2、CD7、CD8 B-ALLCD10、CD19、CD22 、HLA-DR cytogenetics and molecular biology 3 T(15;17)(q22;q21) PML-RARa L1 T(9,22)(q34;q11) BCR-ABL,Acute leukemia,Method：two steps Differential diagnosis Acute leukemia with normal amount of WBCs AA PNH ITP recovery of leukophenia MDS IDA Acute leukemia with higher amount of WBCs infectious monocytosis leukemoid reaction,Diagnosis,Therapy of AL（一）,Supportive medical care,Controlling infection Avoiding bleeding and anemia Hematopoietic Cell factors Protection of important organs,Therapy of AL（二）,Chemotherapy,Purpose： first goal is CR，further Rx to prevent relapse CR(complete remission) symptoms and signs disappear PB：HB100g/l N1.5109/l Pt100109/l with no leukocyte BM Blast cells5% Rules：early, complete, combined intermittent, different stage,Therapy of AL（三）,Chemotherapy,3 stages induction（初治）consolidation（巩固强化）maintenance（维持治疗） leukemic cells 1010-13 106-8 104 （symptom） （CR） （maintenance）,others,Radiotherapy Only for CNSL、Testis leukemia and BMT HSC Transplantation Gene Therapy,Therapy of AL（三）,Hematopoietic stem cell transplantation,permits “rescue” from otherwise excessively toxic treatment additional advantage of graft-vs-leukemia effect in allogeneic transplants trade-off for allogeneic transplantation: greater anti-leukemic effect but more toxic,Factors Age、amount of WBCs、MDS FAB、cytogenetic,Acute leukemia,prognosis,Prognosis,Adult AML,Adult ALL,similar to or worse than AML,Clinical Presentation:,It can occur in any age .But the most age presentation is between 40-60. Symptoms related to hyper metabolism: (weight loss,lassitude,anorexia or night sweats). (Gout or renal impairment caused by hyperuriceamia ). Bone marrow failure: Anemia.,CML Ph +ve Ph ve, BCR-abl +ve Ph ve, BCR-abl -ve Eosinophilic Leukemia Ph: Philadelphia chromosome BCR: Breakpoint cluster region; abl : Abelson oncogene,Chronic myeloid leukemia,Picture 4. Bone marrow film at 400X magnification demonstrates clear dominance of granulopoiesis. The number of eosinophils and megakaryocytes is increased.,Philadelphia :,Is the chromosome which result from the t(9;22)(q34;q11)part of the Abelson proto-oncogene ABL is moved to the BCR gene on chromosome 22 & part of chromosome 22 moves to chromosome 9. The abnormal chromosome 22is the Ph. See fig.,Fig,Investigation:,CBC: Wbc is usually 50X10/l & some times 500X10/l. Normocyt