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1、第六篇 血液(xuy)系统疾病 第九章第九章白血病白血病(Leukemia)周剑峰周剑峰学时学时(xush)(xush)数：数：3 3学时学时(xush)(xush)第一页，共七十二页。-白血病讲授目的(md)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(jxng)白血病FAB分型，联合化疗的原则，完全缓解的概念。第二页，共七十二页。-白血病讲授(jingshu)主要内容概述(i sh)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第三页，共七十二页。-白血病概 述第四页，共七十二页。-白血病Erythrocytes: transport oxyg
2、enErythrocytes: transport oxygenNeutrophilBasophilEosinophilMonocytes/MacrophageDefense against infectionDefense against infectionPlatelets: Mediate blood clottingPlatelets: Mediate blood clottingT-lymphocytes: antigen presenting T-lymphocytes: antigen presenting B-lymphocytesB-lymphocytes Plasma ce
3、ll: Plasma cell:Source of antibodiesSource of antibodies第五页，共七十二页。-白血病Pluripotential stem cellsPluripotential stem cellsMyeloid stem cellsMyeloid stem cellsLymphoid stem cellsLymphoid stem cellsUnipotential progenitor cellsUnipotential progenitor cellsImmature hematopoietic cellsImmature hematopoiet
4、ic cellsmature hematopoietic cellsmature hematopoietic cells第六页，共七十二页。-白血病Hematopoiesis composes of the options of commitment to different lineages Hematopoiesis composes of the options of commitment to different lineages and the progressive stages of maturation at which partial or complete and the
5、progressive stages of maturation at which partial or complete arrest can occur, results in the wide array of malignant disease-Leukemia.arrest can occur, results in the wide array of malignant disease-Leukemia.Stem cell Progenitor cellImmature cellMature cell 第七页，共七十二页。-白血病Accumulation of mutations
6、of DNA within a pluripotential stem cell or very early progenitor cell gives rise to leukemic stem cells.Normal stem cellLeukemic stem cell第八页，共七十二页。-白血病第九页，共七十二页。-白血病第十页，共七十二页。-白血病病因和发病(f bng)机制第十一页，共七十二页。-白血病Etiology&Pathogenesis Environmental factors Acquired diseasesLesions to the DNAClonal expa
7、nsion第十二页，共七十二页。-白血病A lot of environmental factors has been reported to cause leukemia. A lot of environmental factors has been reported to cause leukemia. However, only four of them are firmly established causal agents. However, only four of them are firmly established causal agents. They are:They
8、are:Irradiation exposureIrradiation exposure Chronic benzene exposure Chronic benzene exposure Chemotherapeutic agents Chemotherapeutic agents Leukemia virus infection Leukemia virus infection Environmental factorscause leukemia第十三页，共七十二页。-白血病第十四页，共七十二页。-白血病Inherited syndromes such as ataxia-telangi
9、ectasia, down Inherited syndromes such as ataxia-telangiectasia, down syndrome predispose to subsequent development of leukemia. syndrome predispose to subsequent development of leukemia. Usually, these kinds of syndromes share the common features Usually, these kinds of syndromes share the common f
10、eatures that they all have heretic defects in their genome gave by their that they all have heretic defects in their genome gave by their parents.parents.Inherited syndromes predispose to leukemia第十五页，共七十二页。-白血病Acquired disease predispose to leukemiaLeukemia may also develop from the progression of
11、other clonal disorders of hematopoietic stem cells. Ploycythemia vera, idiopathic myelofibrosis, etc. 第十六页，共七十二页。-白血病Leukemia ClassificationThere are at least dozens of varieties of leukemia. They There are at least dozens of varieties of leukemia. They are classified by how quickly it progresses. A
12、cute are classified by how quickly it progresses. Acute leukemia is fast-growing and can overrun the body within leukemia is fast-growing and can overrun the body within a few weeks or months. By Contrast, chronic leukemia is a few weeks or months. By Contrast, chronic leukemia is slow-growing and p
13、rogressively worsen over years.slow-growing and progressively worsen over years.第十七页，共七十二页。-白血病Acute versus chronic leukemiaAcute: 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
14、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. 第十八页，共七十二页。-白血病Myelogenous versus lymphocyt
15、ic leukemiaIf the leukemic cells arise from myeloid pluripotential stem cells:myeloid leukemia If the leukemic cells arise from lymphocytic pluripotential stem cells:lymphocytic leukemia 第十九页，共七十二页。-白血病临床表现第二十页，共七十二页。-白血病Clinical manifestations Leukemic hematopoiesis Normal hematopoiesismarrow failu
16、reInfiltration第二十一页，共七十二页。-白血病Marrow failureAnemia (loss of erythocytes): fatigues, pallor weakness, reduced exercise tolerance.Fever and infection (Poor infection fighters).Abnormal bleeding (loss of platelets). 第二十二页，共七十二页。-白血病InfiltrationsOral tissue: swollen painful, and bleeding gums.Splenomega
17、ly and hepatomegaly.Lymph node enlargement.Bone or joint pain.CNS-headaches, seizures, weakness, blurred vision and vomiting. 第二十三页，共七十二页。-白血病第二十四页，共七十二页。-白血病实验室检查(jinch)第二十五页，共七十二页。-白血病 Blood test findingsAnemia is a constant feature.Nucleated red cells or immature red blood cell may be present. Th
18、rombocytopenia 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.第二十六页，共七十二页。-白血病Marrow findingsNormal bone marrow AML marrow 第二十七页，共七十二页。-白血病Cytogenetic findings第二十八页，共七十二页。-白血病诊断(zhn
19、dun)标准第二十九页，共七十二页。-白血病Diagnosis & Classification Other newly developed methods第三十页，共七十二页。-白血病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
20、chemical components of cells is conducted to distinguish different types of leukemia. Cytochemistry often use special colored dyes. 第三十一页，共七十二页。-白血病Acute leukemiaAMLALLM0: undifferentiated AMLM0: undifferentiated AMLM1: Myeloblastic leukemia (without maturation)M1: Myeloblastic leukemia (without mat
21、uration)M2: Myeloblastic leukemia (with maturation)M2: Myeloblastic leukemia (with maturation)M3: promyelocytic leukemia M3: promyelocytic leukemia M4: Myelomonocytic leukemiaM4: Myelomonocytic leukemiaM5: Monocytic leukemiaM5: Monocytic leukemiaM6: ErythroleukemiaM6: ErythroleukemiaM7: Megkaryoblas
22、tic leukemiaM7: Megkaryoblastic leukemiaL1: Mature appearing lymphoblasts L1: Mature appearing lymphoblasts L2: Immature and variously shaped lymphoblastsL2: Immature and variously shaped lymphoblastsL3: Lymphoblasts are large and uniform. L3: Lymphoblasts are large and uniform. 第三十二页，共七十二页。-白血病第三十三
23、页，共七十二页。-白血病P142 (CD tables)A lot of CD provides clues for the diagnosis第三十四页，共七十二页。-白血病Flow CytometryFlow CytometryImmunohistochemistry Immunohistochemistry 第三十五页，共七十二页。-白血病 Immnuophenotyping panel used in St. Jude Childrens Immnuophenotyping panel used in St. Jude Childrens research hospital U.S.A
24、. 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.第三十六页，共七十二页。-白血病免疫(miny)表型分型方案T 细胞(xbo)B 细胞(xbo)（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
25、%）前 B-细胞 （9%）早期前-B 细胞 （52%）前-前- B 细胞 （11%）sIg, sIg第三十七页，共七十二页。-白血病第三十八页，共七十二页。-白血病Insert table 90% of the cases with leukemia have non-randomized translocation.第三十九页，共七十二页。-白血病P118 types of translocationsCML AML-M2AML-M3AML-M4AMLAML-M4E0第四十页，共七十二页。-白血病第四十一页，共七十二页。-白血病第四十二页，共七十二页。-白血病第四十三页，共七十二页。-白血病
26、 Other new developed methods第四十四页，共七十二页。-白血病鉴别(jinbi)诊断第四十五页，共七十二页。-白血病Differential DiagnosisPseudoleukemia Myelodysplastic syndrome Nonleukemic pancytopenia 第四十六页，共七十二页。-白血病治 疗第四十七页，共七十二页。-白血病 Treatment1.Supportive cares and preparation of the patients.2.Antileukemic therapy.3.Therapy of the centra
27、l nervous system.4.Stem cell transplantation.第四十八页，共七十二页。-白血病Anemia Hemorrhage Infection第四十九页，共七十二页。-白血病 Hematological supportTransfusion of Platelets Transfusion of packed red cells Transfusions of granulocytes Transfusions of IgG第五十页，共七十二页。-白血病 Infection controlSpecial precautions: protective isol
28、ation Elimination of contaminated foods Oral and digestive system care Broad spectrum antibiotics GM-CSF administration第五十一页，共七十二页。-白血病 Antileukemic therapyChemotherapy to kill leukemia cells using strong anti-cancer drugs第五十二页，共七十二页。-白血病 Treatment phasesInduction therapy: the aim is to bring about
29、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.第五十三页，共七十二页。-白血病 Special subtypes Acute promyelocytic Leukemia (APL): because of the small particles
30、 (procoagulants) inside the APL cell, DIC are commonly seen in this type of AML.第五十四页，共七十二页。-白血病Normal APLGenes essential for differentiation are shut down by the fusion proteins PML-RARalpha第五十五页，共七十二页。-白血病Differentiation agents (all-trans retinoic acid, arsenic trioxide)第五十六页，共七十二页。-白血病Hyperleukec
31、ytosis: cause a batch of complications and should be treated using leukapheresis ( exchanging transfusion) or preinduction treatment prior to intensive chemotherapy. 第五十七页，共七十二页。-白血病 Acute leukemia over 60 years of age is less responsive to chemotherapy. Standard two-drugs therapy can be used. CR 30
32、%Intolerant to standard therapy. Low-dose of Ara-C can be used for 1428 days.第五十八页，共七十二页。-白血病 Therapy of the CNS leukemiaThe 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
33、 CNS leukemia such as AML (M4, M5), ALL. 第五十九页，共七十二页。-白血病Intrathecal chemotherapyCranial irradiation第六十页，共七十二页。-白血病 Stem cell transplantationsThe 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.
34、 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. 第六十一页，共七十二页。-白血病 Three types of transplantation performedAllogeneic transplantatio
35、n (HLA-matched individual donors)Syngeneic transplantation: identical twins.Autologous transplantation: patients receive their own stem cells第六十二页，共七十二页。-白血病Clinical results of stem cell transplantationAML ALL CMLFive-years disease free survival rate Five-years disease free survival rate Transplanta
36、tionChemotherapy第六十三页，共七十二页。-白血病 Chronic myelogenous leukemia (CML)第六十四页，共七十二页。-白血病第六十五页，共七十二页。-白血病第六十六页，共七十二页。-白血病第六十七页，共七十二页。-白血病Future directions第六十八页，共七十二页。-白血病第六十九页，共七十二页。-白血病第七十页，共七十二页。-白血病复习(fx)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(ychng)综合征的分型、临床表现、与急性 白血病的关系？第七十一页，共七十二页。-白血病内容(nirng)总结第六篇 血液系统疾病。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。CD7（敏感），cCD3 （特异）。3.骨髓增生(zngshng)异常综合征的分型、临床表现、与急性。白血病的关系第七十二页，共七十二页。-白血病
