内科学课件：第六篇 血液系统疾病 第九章 白血病

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 oxygenNeutrophilBasophilEosinophilMonocytes/MacrophageDefense against infectionPlatelets: Mediate blood clottingT-lymphocytes: antigen pres

2、enting B-lymphocytes Plasma cell:Source of antibodiesPluripotential stem cellsMyeloid stem cellsLymphoid stem cellsUnipotential progenitor cellsImmature hematopoietic cellsmature hematopoietic cellsHematopoiesis composes of the options of commitment to different lineages and the progressive stages o

3、f maturation at which partial or complete arrest can occur, results in the wide array of malignant disease-LeukemiaStem cell Progenitor cellImmature cellMature cell Accumulation of mutations of DNA within a pluripotential stem cell or very early progenitor cell gives rise to leukemic stem cellsNorma

4、l stem cellLeukemic stem cellEtiology&Pathogenesis Environmental factors Acquired diseasesLesions to the DNAClonal expansionA 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 benze

5、ne exposure Chemotherapeutic agents Leukemia virus infection Environmental factorscause leukemiaInherited 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 de

6、fects in their genome gave by their parentsInherited syndromes predispose to leukemiaAcquired disease predispose to leukemiaLeukemia may also develop from the progression of other clonal disorders of hematopoietic stem cells. Ploycythemia vera, idiopathic myelofibrosis, etc Leukemia ClassificationTh

7、ere 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 yearsAcute versus chronic leukemiaAcut

8、e: 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 monthsChronic: in Chronic leukemia, the blood cells eventually mature, or partially mature. But t

9、hey are not “normal”. They remain in the blood much longer than normal blood cells and they can not act functional cells wellMyelogenous versus lymphocytic leukemiaIf the leukemic cells arise from myeloid pluripotential stem cells:myeloid leukemia If the leukemic cells arise from lymphocytic pluripo

10、tential stem cells:lymphocytic leukemia Clinical manifestations Leukemic hematopoiesis Normal hematopoiesismarrow failureInfiltrationMarrow failureAnemia (loss of erythocytes): fatigues, pallor weakness, reduced exercise toleranceFever and infection (Poor infection fighters)Abnormal bleeding (loss o

11、f platelets)InfiltrationsOral tissue: swollen painful, and bleeding gumsSplenomegaly and hepatomegalyLymph node enlargementBone or joint painCNS-headaches, seizures, weakness, blurred vision and vomiting Blood test findings Anemia is a constant feature.Nucleated red cells or immature red blood cell

12、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 bloodMarrow findingsNormal bone marrow AML marrow Cytogenetic findingsDiagnosis & Classification Other newl

13、y developed methodsMorphology : the bone marrow cells are evaluated according to their size,shape, and content of granules and then they are classified with respected to maturityCytochemistry staining: identification of the chemical components of cells is conducted to distinguish different types of

14、leukemia. Cytochemistry often use special colored dyes Acute leukemiaAMLALLM0: undifferentiated AMLM1: Myeloblastic leukemia (without maturation)M2: Myeloblastic leukemia (with maturation)M3: promyelocytic leukemia M4: Myelomonocytic leukemiaM5: Monocytic leukemiaM6: ErythroleukemiaM7: Megkaryoblast

15、ic leukemiaL1: Mature appearing lymphoblasts L2: Immature and variously shaped lymphoblastsL3: Lymphoblasts are large and uniform P142 (CD tables)A lot of CD provides clues for the diagnosisFlow CytometryImmunohistochemistry Immnuophenotyping panel used in St. Jude Childrens research hospital U.S.A.

16、 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, sIgInsert ta

17、ble 90% of the cases with leukemia have non-randomized translocationP118 types of translocationsCML AML-M2AML-M3AML-M4AMLAML-M4E0 Other new developed methodsDifferential DiagnosisPseudoleukemia Myelodysplastic syndrome Nonleukemic pancytopenia TreatmentSupportive cares and preparation of the patient

18、sAntileukemic therapyTherapy of the central nervous systemStem cell transplantationAnemia Hemorrhage Infection Hematological supportTransfusion of Platelets Transfusion of packed red cells Transfusions of granulocytes Transfusions of IgG Infection controlSpecial precautions: protective isolation Eli

19、mination of contaminated foods Oral and digestive system care Broad spectrum antibiotics GM-CSF administration Antileukemic therapyChemotherapy to kill leukemia cells using strong anti-cancer drugs Treatment phasesInduction therapy: the aim is to bring about remission , that is leukemic cells are no

20、 longer found in the bone marrow and the recovery of normal hematopoiesisPost-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

21、 in this type of AMLNormal APLGenes essential for differentiation are shut down by the fusion proteins PML-RARalphaDifferentiation agents (all-trans retinoic acid, arsenic trioxide)Hyperleukecytosis: cause a batch of complications and should be treated using leukapheresis ( exchanging transfusion) o

22、r preinduction treatment prior to intensive chemotherapy 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 Therapy of the CNS leukemiaThe CNS is a frequent s

23、anctuary 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), ALLIntrathecal chemotherapyCranial irradiation Stem cell transplantationsThe main purpose of BMT and PBSCT in cancer treatment is to make it p