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第六篇 血液系统疾病 第九章 白血病 (Leukemia) 学时数:2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 oxygenErythrocytes: transport oxygen Neutrophil Basophil Eosinophil Monocytes/Macrophage Defense against infectionDefense against infection Platelets: Mediate blood clottingPlatelets: Mediate blood clotting T-lymphocytes: antigen presenting T-lymphocytes: antigen presenting B-lymphocytesB-lymphocytes Plasma cell: Plasma cell: Source of antibodiesSource of antibodies Leukemia ClassificationLeukemia Classification There are at least dozens of varieties of leukemia. There are at least dozens of varieties of leukemia. They are classified by how quickly it progresses. They are classified by how quickly it progresses. Acute leukemia is fast-growing and can overrun the Acute leukemia is fast-growing and can overrun the body within a few weeks or months. By Contrast, body within a few weeks or months. By Contrast, chronic leukemia is slow-growing and progressively chronic leukemia is slow-growing and progressively worsen over yearsworsen over years Acute versus chronic leukemiaAcute 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 pluripotentia l stem cells: myeloid leukemia If the leukemic cells arise from lymphocytic pluripotentia l stem cells: lymphocytic leukemia Clinical manifestations Clinical manifestations Leukemic hematopoiesis Normal hematopoiesis marrow failuremarrow failureInfiltrationInfiltration Marrow failureMarrow failure Anemia (loss of Anemia (loss of erythocyteserythocytes): fatigues, ): fatigues, pallor weakness, reduced exercise pallor weakness, reduced exercise tolerancetolerance Fever and infection (Poor infection Fever and infection (Poor infection fighters)fighters) Abnormal bleeding (loss of platelets)Abnormal bleeding (loss of platelets) InfiltrationsInfiltrations Oral tissue: swollen painful, and bleeding gumsOral tissue: swollen painful, and bleeding gums SplenomegalySplenomegaly and and hepatomegalyhepatomegaly Lymph node enlargementLymph node enlargement Bone or joint painBone or joint pain CNS-headaches, seizures, weakness, blurred CNS-headaches, seizures, weakness, blurred vision and vomiting vision and vomiting Blood test findingsBlood 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 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 AMLM0: undifferentiated AML M1: Myeloblastic leukemia (without maturation)M1: Myeloblastic leukemia (without maturation) M2: Myeloblastic leukemia (with maturation)M2: Myeloblastic leukemia (with maturation) M3: promyelocytic leukemia M3: promyelocytic leukemia M4: Myelomonocytic leukemiaM4: Myelomonocytic leukemia M5: Monocytic leukemiaM5: Monocytic leukemia M6: ErythroleukemiaM6: Erythroleukemia M7: Megkaryoblastic leukemiaM7: Megkaryoblastic leukemia L1: Mature appearing lymphoblasts L1: Mature appearing lymphoblasts L2: Immature and variously shaped lymphoblastsL2: Immature and variously shaped lymphoblasts L3: Lymphoblasts are large and uniform L3: Lymphoblasts are large and uniform ImmnuophenotypingImmnuophenotyping panel used in St. Jude Childrens panel used in St. Jude Childrens research hospital U.S.A. 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 Differential DiagnosisDifferential Diagnosis Pseudoleukemia Myelodysplastic syndrome Nonleukemic pancytopenia Treatment Treatment 1. Supportive cares and preparation of the patients 2. Antileukemic therapy 3. Therapy of the central nervous system 4. Stem cell transplantation Infection controlInfection control Special precautions: protective isolation Special precautions: protective isolation Elimination of contaminated foods Elimination of contaminated foods Oral and digestive system care Oral and digestive system care Broad spectrum antibiotics Broad spectrum antibiotics GM-CSF administrationGM-CSF administration Treatment phases Treatment phases Induction therapy:Induction therapy: the aim is to bring about the aim is to bring about remission , that is remission , that is leukemicleukemic cells are no longer cells are no longer found in the bone marrow and the recovery of found in the bone marrow and the recovery of normal normal hematopoiesishematopoiesis Post-remission therapy:Post-remission therapy: to eliminate any to eliminate any leukemia cells potential hiding in the bodyleukemia cells potential hiding in the body Normal APL Genes essential for differentiation are shut down Genes essential for differentiation are shut down by the fusion proteins PML-by the fusion proteins PML-RARalphaRARalpha Therapy of the CNS leukemia 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 Stem cell transplantations 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 typ
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