白血病英文课件

1、第六篇 血液(xuy)系统疾病 第九章白血病(Leukemia)周剑峰学时数：3学时(xush)共六十四页讲授(jingshu)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(zhndun)标准，治疗原则2.熟悉急性白血病FAB分型，联合化疗的原则，完全缓解的概念共六十四页讲授(jingshu)主要内容概述病因和发病机制临床表现实验室检查诊断(zhndun)标准鉴别诊断治疗共六十四页Erythrocytes: transport oxygenNeutrophilBasophilEosinophilMonocytes/MacrophageDefense against infect

2、ionPlatelets: Mediate blood clottingT-lymphocytes: antigen presenting B-lymphocytes Plasma cell:Source of antibodies共六十四页Pluripotential stem cellsMyeloid stem cellsLymphoid stem cellsUnipotential progenitor cellsImmature hematopoietic cellsmature hematopoietic cells共六十四页Hematopoiesis composes of the

3、 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-LeukemiaStem cell Progenitor cellImmature cellMature cell 共六十四页Accumulation of mutations of DNA within a pluripotential

4、stem cell or very early progenitor cell gives rise to leukemic stem cellsNormal stem cellLeukemic stem cell共六十四页共六十四页共六十四页Etiology&Pathogenesis Environmental factors Acquired diseasesLesions to the DNAClonal expansion共六十四页A lot of environmental factors has been reported to cause leukemia. However, o

5、nly four of them are firmly established causal agents. They are:Irradiation exposure Chronic benzene exposure Chemotherapeutic agents Leukemia virus infection Environmental factorscause leukemia共六十四页共六十四页Inherited syndromes such as ataxia-telangiectasia, down syndrome predispose to subsequent develo

6、pment of leukemia. Usually, these kinds of syndromes share the common features that they all have heretic defects in their genome gave by their parentsInherited syndromes predispose to leukemia共六十四页Acquired disease predispose to leukemiaLeukemia may also develop from the progression of other clonal

7、disorders of hematopoietic stem cells. Ploycythemia vera, idiopathic myelofibrosis, etc 共六十四页Leukemia ClassificationThere 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 mont

8、hs. By Contrast, chronic leukemia is slow-growing and progressively worsen over years共六十四页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 diseas

9、e may be fatal within few monthsChronic: 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共六十四页Myelogenous versus lymphocytic leukemiaIf the l

10、eukemic cells arise from myeloid pluripotential stem cells:myeloid leukemia If the leukemic cells arise from lymphocytic pluripotential stem cells:lymphocytic leukemia 共六十四页Clinical manifestations Leukemic hematopoiesis Normal hematopoiesismarrow failureInfiltration共六十四页Marrow failureAnemia (loss of

11、 erythocytes): fatigues, pallor weakness, reduced exercise toleranceFever and infection (Poor infection fighters)Abnormal bleeding (loss of platelets)共六十四页InfiltrationsOral tissue: swollen painful, and bleeding gumsSplenomegaly and hepatomegalyLymph node enlargementBone or joint painCNS-headaches, s

12、eizures, weakness, blurred vision and vomiting 共六十四页共六十四页 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

13、 hematopoietic cells are almost present in the blood共六十四页Marrow findingsNormal bone marrow AML marrow 共六十四页Cytogenetic findings共六十四页Diagnosis & Classification Other newly developed methods共六十四页Morphology : the bone marrow cells are evaluated according to their size,shape, and content of granules and

14、 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.共六十四页共六十四页Acute leukemiaAMLALLM0: undifferentiated AMLM1: Myeloblastic

15、 leukemia (without maturation)M2: Myeloblastic leukemia (with maturation)M3: promyelocytic leukemia M4: Myelomonocytic leukemiaM5: Monocytic leukemiaM6: ErythroleukemiaM7: Megkaryoblastic leukemiaL1: Mature appearing lymphoblasts L2: Immature and variously shaped lymphoblastsL3: Lymphoblasts are lar

16、ge and uniform 共六十四页P142 (CD tables)A lot of CD provides clues for the diagnosis共六十四页Flow CytometryImmunohistochemistry 共六十四页 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

17、analysis, one can make a firm diagnosis in 99% of cases共六十四页免疫(miny)表型分型方案T 细胞(xbo)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共六十四页共六十四页Insert table 90% of the cases with leukemia have non-randomized translocation共六十四页

18、P118 types of translocationsCML AML-M2AML-M3AML-M4AMLAML-M4E0共六十四页共六十四页共六十四页共六十四页 Other new developed methods共六十四页Differential DiagnosisPseudoleukemia Myelodysplastic syndrome Nonleukemic pancytopenia 共六十四页 TreatmentSupportive cares and preparation of the patientsAntileukemic therapyTherapy of the c

19、entral nervous systemStem cell transplantation共六十四页Anemia Hemorrhage Infection共六十四页 Hematological supportTransfusion of Platelets Transfusion of packed red cells Transfusions of granulocytes Transfusions of IgG共六十四页 Infection controlSpecial precautions: protective isolation Elimination of contaminat

20、ed foods Oral and digestive system care Broad spectrum antibiotics GM-CSF administration共六十四页 Antileukemic therapyChemotherapy to kill leukemia cells using strong anti-cancer drugs共六十四页 Treatment phasesInduction therapy: the aim is to bring about remission , that is leukemic cells are no longer foun

21、d in the bone marrow and the recovery of normal hematopoiesisPost-remission therapy: to eliminate any leukemia cells potential hiding in the body共六十四页 Special subtypes Acute promyelocytic Leukemia (APL): because of the small particles (procoagulants) inside the APL cell, DIC are commonly seen in thi

22、s type of AML共六十四页Normal APLGenes essential for differentiation are shut down by the fusion proteins PML-RARalpha共六十四页Differentiation agents (all-trans retinoic acid, arsenic trioxide)共六十四页Hyperleukecytosis: cause a batch of complications and should be treated using leukapheresis ( exchanging transf

23、usion) or preinduction treatment prior to intensive chemotherapy 共六十四页 Acute leukemia over 60 years of age is less responsive to chemotherapyStandard two-drugs therapy can be used. CR 30%Intolerant to standard therapy. Low-dose of Ara-C can be used for 14-28 days共六十四页 Therapy of the CNS leukemiaThe

24、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共六十四页Intrathecal chemotherapyCranial irradiation共六十四页 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 r