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1、第六篇 血液系统疾病,第九章,白血病 (Leukemia),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-lym
2、phocytes: 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 lineage
3、s 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
4、 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
5、 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 com
6、mon 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
7、 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 wors
8、en 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 ce
9、lls 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,
10、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 in
11、fection (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
12、 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,A
13、ML 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 chemic
14、al 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: Myelo
15、monocytic 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,Immunohistoc
16、hemistry,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),
17、 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,
18、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
19、 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-c
20、ancer 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 pro
21、myelocytic 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)
22、,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% Intol
23、erant 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
24、 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 a
25、nd 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: identic
26、al 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？,