第六篇-第九章-白血病.ppt

,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,第六篇 血液系统疾病,第九章,白血病,(,Leukemia,),周剑峰,学时数：,3,学时,讲授目的和要求,1.掌握急、慢性白血病的临床表现，实验室检查及诊断标准，治疗原则,2.熟悉急性白血病,FAB,分型，联合化疗的原则，完全缓解的概念,讲授主要内容,概述,病因和发病机制,临床表现,实验室检查,诊断标准,鉴别诊断,治疗,Erythrocytes:transport oxygen,Neutrophil,Basophil,Eosinophil,Monocytes,/Macrophage,Defense against infection,Platelets:Mediate blood clotting,T-lymphocytes:antigen presenting,B-lymphocytes,Plasma cell:,Source of antibodies,Pluripotential,stem cells,Myeloid stem cells,Lymphoid stem cells,Unipotential,progenitor cells,Immature,hematopoietic,cells,mature,hematopoietic,cells,Hematopoiesis composes of the options of commitment to different lineages and the progressive stages of maturation at which partial or complete arrest can occur,results in the wide array of malignant disease-Leukemia,Stem cell,Progenitor cell,Immature cell,Mature cell,Accumulation of mutations of DNA within a,pluripotential,stem cell or very early progenitor cell gives rise to leukemic stem cells,Normal stem cell,Leukemic stem cell,Etiology&Pathogenesis,Environmental factors,Acquired diseases,Lesions to the DNA,Clonal,expansion,A lot of environmental factors has been reported to cause leukemia.However,only four of them are firmly established causal agents.They are:,Irradiation exposure,Chronic benzene exposure,Chemotherapeutic agents,Leukemia virus infection,Environmental factors,cause leukemia,Inherited syndromes such as ataxia-,telangiectasia,down syndrome predispose to subsequent development of leukemia.Usually,these kinds of syndromes share the common features that they all have heretic defects in their genome gave by their parents,Inherited syndromes predispose to leukemia,Acquired disease predispose to leukemia,Leukemia may also develop from the progression of other,clonal,disorders of,hematopoietic,stem cells.,Ploycythemia vera,idiopathic,myelofibrosis,etc,Leukemia Classification,There are at least dozens of varieties of leukemia.They are classified by how quickly it progresses.Acute leukemia is fast-growing and can overrun the body within a few weeks or months.By Contrast,chronic leukemia is slow-growing and progressively worsen over years,Acute versus chronic leukemia,Acute:,the blood cells of acute leukemia remain in an immature state,so they reproduce and accumulate very rapidly.Therefore,they need treatment immediately,otherwise the disease may be fatal within few months,Chronic:,in Chronic leukemia,the blood cells eventually mature,or partially mature.But they are not “normal”.They remain in the blood much longer than normal blood cells and they can not act functional cells well,Myelogenous,versus,lymphocytic leukemia,If the,leukemic,cells arise from myeloid,pluripotential,stem cells:,myeloid leukemia,If the,leukemic,cells arise from lymphocytic,pluripotential,stem cells:,lymphocytic leukemia,Clinical manifestations,Leukemic hematopoiesis,Normal,hematopoiesis,marrow failure,Infiltration,Marrow failure,Anemia(loss of,erythocytes,):fatigues,pallor weakness,reduced exercise tolerance,Fever and infection(Poor infection fighters),Abnormal bleeding(loss of platelets),Infiltrations,Oral tissue:swollen painful,and bleeding gums,Splenomegaly,and,hepatomegaly,Lymph node enlargement,Bone or joint pain,CNS-headaches,seizures,weakness,blurred vision and vomiting,Blood test findings,Anemia is a constant feature.Nucleated red cells or immature red blood cell may be present.,Thrombocytopenia,is nearly always present at the time of diagnosis.,The total leukocyte counts can be high,normal or low.,Immature,hematopoietic,cells are almost present in the blood,Marrow findings,Normal bone marrow,AML marrow,Cytogenetic,findings,Diagnosis&Classification,Other newly developed,methods,Morphology:the bone marrow cells are evaluated according to their size,shape,and content of granules and then they are classified with respected to maturity,Cytochemistry,staining:identification of the chemical components of cells is conducted to distinguish different types of leukemia.,Cytochemistry,often use special colored dyes,Acute leukemia,AML,ALL,M0:undifferentiated AML,M1:Myeloblastic leukemia(without maturation),M2:Myeloblastic leukemia(with maturation),M3:promyelocytic leukemia,M4:Myelomonocytic leukemia,M5:Monocytic leukemia,M6:Erythroleukemia,M7:Megkaryoblastic leukemia,L1:Mature appearing lymphoblasts,L2:Immature and variously shaped lymphoblasts,L3:Lymphoblasts are large and uniform,P142(CD tables),A lot of CD provides clues for the diagnosis,Flow Cytometry,Immunohistochemistry,Immnuophenotyping,panel used in St.Jude Childrens,research hospital U.S.A.,CD13 CD33 CD19 CytoCD79a CD7 CytoCD3,AML -,B-ALL -,T-ALL -,By using this method of analysis,one can make a firm diagnosis in 99%of cases,免疫表型分型方案,T,细胞,B,细胞（4%）,B,细胞前体,CD7（,敏感），,cCD3（,特异）,CD19(,敏感,),cCD79a(,特异,),成熟,T,细胞（18%）,前,T,细胞（6%）,前,B-,细胞（9%）,早期前-,B,细胞（52%）,前-前-,B,细胞（11%）,sIg,sIg,Insert table,90%,of the cases with leukemia have non-randomized translocation,P118 types of translocations,CML,AML-M2,AML-M3,AML-M4,AML,AML-M4E0,Other new developed methods,Differential Diagnosis,Pseudoleukemia,Myelodysplastic syndrome,Nonleukemic pancytopenia,Treatment,Supportive cares and preparation of the patients,Antileukemic therapy,Therapy of the central nervous system,Stem cell transplantation,Anemia,Hemorrhage,Infection,Hematological support,Transfusion of Platelets,Transfusion of packed red cells,Transfusions of,granulocytes,Transfusions of,IgG,Infection control,Special precautions:protective isolation,Elimination of contaminated foods,Oral and digestive system care,Broad spectrum antibiotics,GM-CSF administration,Antileukemic therapy,Chemotherapy to kill leukemia cells using strong anti-cancer drugs,Treatment phases,Induction therapy:,the aim is to bring about remission,that is,leukemic,cells are no longer found in the bone marrow and the recovery of normal,hematopoiesis,Post-remission therapy:,to eliminate any leukemia cells potential hiding in the body,Special subtypes,Acute promyelocytic Leukemia(APL),:because of the small particles(,procoagulants,)inside the APL cell,DIC are commonly seen in this type of AML,Normal,APL,Genes essential for differentiation are shut down by the fusion proteins PML-,RARalpha,Differentiation agents(all-trans,retinoic,acid,arsenic trioxide),Hyperleukecytosis,:,cause a batch of complications and should be treated using,leukapheresis,(exchanging transfusion)or,preinduction,treatment prior to intensive chemotherapy,Acute leukemia over 60 years of age is less responsive to chemotherapy,Standard two-drugs therapy can be used.CR 30%,Intolerant to standard therapy.Low-dose of,Ara,-C can be used for 14-28 days,Therapy of the CNS leukemia,The CNS is a frequent sanctuary site for,leukemic,cells because most of the chemotherapy drugs are not able to reach the CNS.Some types of acute leukemia have tendency to be with CNS leukemia such as AML(M4,M5),ALL,Intrathecal,chemotherapy,Cranial irradiation,Stem cell transplantations,The main purpose of BMT and PBSCT in cancer treatment is to make it possible for patients to receive very high doses of chemotherapy and/or radiation therapy.In addition,re-established normal,hematopoiesis,and immune system by the healthy stem cells fight against leukemia effectively.So it change the vision in the medical history that leukemia is incurable malignancies,Three types of transplantation performed,Allogeneic,transplantation,(HLA-matched individual donors),Syngeneic,transplantation:,identical twins,Autologous,transplantation:,patients receive their own stem cells,Clinical results of stem cell transplantation,AML ALL CML,Five-years disease free survival rate,Transplantation,Chemotherapy,Chronic myelogenous leukemia(CML),Future directions,复习思考题,1.慢性粒细胞白血病与类白血病反应的鉴别要点？,2,.白血病完全缓解的标准？为何要进行巩固、,强化化疗？,3.骨髓增生异常综合征的分型、临床表现、与急性,白血病的关系？,