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 oxygenNeutrophilBasophilDefense against infectionEosinophilMonocytes/MacrophagePlatelets:Mediate blood clottingT-lymphocytes:antigen presenti
2、ng B-lymphocytesPlasma cell:Source of antibodiesMyeloid stem cellsPluripotential stem cellsLymphoid stem cellsUnipotential progenitor cellsImmature hematopoietic cellsmature hematopoietic cellsHematopoiesis composes of the options of commitment to different lineages and the progressive stages of mat
3、uration at which partial or complete arrest can occur,results in the wide array of malignant disease-LeukemiaProgenitor cellMature cell Accumulation of mutations of DNA within a pluripotential stem cell or very early progenitor cell gives rise to leukemic stem cellsNormal stem cellLeukemic stem cell
4、Etiology&Pathogenesis Environmental factorsLesions to the DNAAcquired diseasesClonal expansionEnvironmental factorscause leukemiaA lot of environmental factors has been reported to cause leukemia.However,only four of them are firmly established causal agents.They are:Irradiation exposureChronic benz
5、ene exposureChemotherapeutic agents Leukemia virus infection Inherited syndromes predispose to 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 hereti
6、c defects in their genome gave by their parentsAcquired disease predispose to leukemiaLeukemia may also develop from the progression of other clonal disorders of hematopoietic stem cells.Ploycythemia vera,idiopathic myelofibrosis,etc Leukemia ClassificationThere are at least dozens of varieties of l
7、eukemia.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 leukemiaAcute:the blood cells of acute leukemia remain in
8、 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 they are not “normal”.They remain in the blood much lon
9、ger 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 pluripotential stem cells:lymphocytic leukemia Clinical manife
10、stations Normal hematopoiesisLeukemic hematopoiesisInfiltrationmarrow failureMarrow failureAnemia(loss of erythocytes):fatigues,pallor weakness,reduced exercise toleranceFever and infection(Poor infection fighters)Abnormal bleeding(loss of platelets)InfiltrationsOral tissue:swollen painful,and bleed
11、ing gumsSplenomegaly and hepatomegalyLymph node enlargementBone or joint painCNS-headaches,seizures,weakness,blurred vision and vomiting Blood test findingsAnemia is a constant feature.Nucleated red cells or immature red blood cell may be present.Thrombocytopenia is nearly always present at the time
12、 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 newly developed methodsMorphology:the bone marrow cells are evaluated accordi
13、ng 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 leukemia.Cytochemistry often use special colored dyes M0:undifferentiated AML
14、M1:Myeloblastic leukemia(without maturation)AMLM2:Myeloblastic leukemia(with maturation)M3:promyelocytic leukemia M4:Myelomonocytic leukemiaM5:Monocytic leukemiaAcute leukemiaM6:ErythroleukemiaM7:Megkaryoblastic leukemiaALLL1:Mature appearing lymphoblasts L2:Immature and variously shaped lymphoblast
15、sL3: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.CD13 CD33 CD19 CytoCD79a CD7 CytoCD3 AML -B-ALL -T-ALL -By using this method of analysis,one
16、can make a firm diagnosis in 99%of cases免疫表型分型方案CD19(敏感),cCD79a(特异)CD7（敏感），cCD3（特异）T 细胞成熟T 细胞（18%）前 T 细胞（6%）B 细胞（4%）sIg?,sIg?B 细胞前体前 B-细胞（9%）早期前-B 细胞（52%）前-前-B 细胞（11%）Insert table 90%of the cases with leukemia have non-randomized translocationCML P118 types of translocationsAML-M2AML-M4E0AML-M3AML-M
17、4AMLOther new developed methodsDifferential DiagnosisPseudoleukemia Myelodysplastic syndrome Nonleukemic pancytopenia Treatment1.Supportive cares and preparation of the patients2.Antileukemic therapy3.Therapy of the central nervous system4.Stem cell transplantationAnemiaHemorrhage InfectionHematolog
18、ical supportTransfusion of PlateletsTransfusion of packed red cellsTransfusions of granulocytes Transfusions of IgGInfection controlSpecial precautions:protective isolation Elimination of contaminated foods Oral and digestive system care Broad spectrum antibiotics GM-CSF administrationAntileukemic t
19、herapyChemotherapy to kill leukemia cells using strong anti-cancer drugsTreatment phasesInduction 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 hematopoiesisPost-remission therapy:to eliminate any leukemia cells p
20、otential hiding in the bodySpecial subtypes Acute promyelocytic Leukemia(APL):because of the small particles(procoagulants)inside the APL cell,DIC are commonly seen in this type of AMLGenes essential for differentiation are shut down by the fusion proteins PML-RARalphaNormalAPLDifferentiation agents
21、(all-trans retinoic acid,arsenic trioxide)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 chemotherapyStandard two-dru
22、gs therapy can be used.CR 30%Intolerant to standard therapy.Low-dose of Ara-C can be used for 14-28 daysTherapy 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 t
23、o be with CNS leukemia such as AML(M4,M5),ALLIntrathecal chemotherapyCranial irradiationStem 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.In addition,re-established n
24、ormal 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 malignanciesThree types of transplantation performedAllogeneic transplantation(HLA-matched individual donors)Syngeneic transpla
25、ntation:identical twinsAutologous transplantation:patients receive their own stem cellsClinical results of stem cell transplantation etar la90%viv80%rus70%eer60%f e50%sae40%si d30%sra20%ey-10%eviF0%TransplantationChemotherapyAML ALL CML123Chronic 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？
