1、第六篇 血液系統(tǒng)疾病,第九章,白血病 (Leukemia),學(xué)時數(shù)：3學(xué)時,1,薈萃醫(yī)學(xué),講授目的和要求,1.掌握急、慢性白血病的臨床表現(xiàn)，實驗室檢查及診斷標(biāo)準(zhǔn)，治療原則 2.熟悉急性白血病FAB分型，聯(lián)合化療的原則，完全緩解的概念,2,薈萃醫(yī)學(xué),講授主要內(nèi)容,概述 病因和發(fā)病機(jī)制 臨床表現(xiàn) 實驗室檢查 診斷標(biāo)準(zhǔn) 鑒別診斷 治療,3,薈萃醫(yī)學(xué),Erythrocytes: transport oxygen,Neutrophil Basophil Eosinophil Monocytes/Macrophage,Defense against infection,Platelets: Mediate

2、 blood clotting,T-lymphocytes: antigen presenting,B-lymphocytes Plasma cell:,Source of antibodies,4,薈萃醫(yī)學(xué),Pluripotential stem cells,Myeloid stem cells,Lymphoid stem cells,Unipotential progenitor cells,Immature hematopoietic cells,mature hematopoietic cells,5,薈萃醫(yī)學(xué),Hematopoiesis composes of the options

3、 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-Leukemia,Stem cell,Progenitor cell,Immature cell,Mature cell,6,薈萃醫(yī)學(xué),Accumulation of mutations of DNA within a pluripotential ste

4、m cell or very early progenitor cell gives rise to leukemic stem cells,Normal stem cell,Leukemic stem cell,7,薈萃醫(yī)學(xué),8,薈萃醫(yī)學(xué),9,薈萃醫(yī)學(xué),Etiology&Pathogenesis,Environmental factors Acquired diseases,Lesions to the DNA,Clonal expansion,10,薈萃醫(yī)學(xué),A lot of environmental factors has been reported to cause leukemia

5、. However, only four of them are firmly established causal agents. They are: Irradiation exposure Chronic benzene exposure Chemotherapeutic agents Leukemia virus infection,Environmental factors cause leukemia,11,薈萃醫(yī)學(xué),12,薈萃醫(yī)學(xué),Inherited syndromes such as ataxia-telangiectasia, down syndrome predispose

6、 to subsequent development of leukemia. Usually, these kinds of syndromes share the common features that they all have heretic defects in their genome gave by their parents,Inherited syndromes predispose to leukemia,13,薈萃醫(yī)學(xué),Acquired disease predispose to leukemia,Leukemia may also develop from the p

7、rogression of other clonal disorders of hematopoietic stem cells. Ploycythemia vera, idiopathic myelofibrosis, etc,14,薈萃醫(yī)學(xué),Leukemia Classification,There 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

8、body within a few weeks or months. By Contrast, chronic leukemia is slow-growing and progressively worsen over years,15,薈萃醫(yī)學(xué),Acute 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 treatme

9、nt 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,16,薈萃醫(yī)學(xué),Myelog

10、enous versus lymphocytic leukemia,If the leukemic cells arise from myeloid pluripotential stem cells: myeloid leukemia,If the leukemic cells arise from lymphocytic pluripotential stem cells: lymphocytic leukemia,17,薈萃醫(yī)學(xué),Clinical manifestations,Leukemic hematopoiesis,Normal hematopoiesis,marrow failu

11、re,Infiltration,18,薈萃醫(yī)學(xué),Marrow failure,Anemia (loss of erythocytes): fatigues, pallor weakness, reduced exercise tolerance Fever and infection (Poor infection fighters) Abnormal bleeding (loss of platelets),19,薈萃醫(yī)學(xué),Infiltrations,Oral tissue: swollen painful, and bleeding gums Splenomegaly and hepato

12、megaly Lymph node enlargement Bone or joint pain CNS-headaches, seizures, weakness, blurred vision and vomiting,20,薈萃醫(yī)學(xué),21,薈萃醫(yī)學(xué),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 dia

13、gnosis.The total leukocyte counts can be high, normal or low. Immature hematopoietic cells are almost present in the blood,22,薈萃醫(yī)學(xué),Marrow findings,Normal bone marrow,AML marrow,23,薈萃醫(yī)學(xué),Cytogenetic findings,24,薈萃醫(yī)學(xué),Diagnosis & Classification,Other newly developed methods,25,薈萃醫(yī)學(xué),Morphology : the bone

14、 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 speci

15、al colored dyes,26,薈萃醫(yī)學(xué),Acute leukemia,AML,ALL,M0: undifferentiated AML M1: Myeloblastic leukemia (without maturation) M2: Myeloblastic leukemia (with maturation) M3: promyelocytic leukemia M4: Myelomonocytic leukemia M5: Monocytic leukemia M6: Erythroleukemia M7: Megkaryoblastic leukemia L1: Mature

16、 appearing lymphoblasts L2: Immature and variously shaped lymphoblasts L3: Lymphoblasts are large and uniform,27,薈萃醫(yī)學(xué),28,薈萃醫(yī)學(xué),P142 (CD tables),A lot of CD provides clues for the diagnosis,29,薈萃醫(yī)學(xué),Flow Cytometry,Immunohistochemistry,30,薈萃醫(yī)學(xué),Immnuophenotyping panel used in St. Jude Childrens research

17、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,31,薈萃醫(yī)學(xué),免疫表型分型方案,T 細(xì)胞,B 細(xì)胞（4%）,B 細(xì)胞前體,CD7（敏感），cCD3 （特異）,CD19 (敏感), cCD79a (特異),成熟T 細(xì)胞 （18%）,前 T 細(xì)胞（6%）,前 B-細(xì)胞 （9%）,早期前-B 細(xì)胞 （52

18、%）,前-前- B 細(xì)胞 （11%）,sIg, sIg,32,薈萃醫(yī)學(xué),33,薈萃醫(yī)學(xué),Insert table,90% of the cases with leukemia have non-randomized translocation,34,薈萃醫(yī)學(xué),P118 types of translocations,CML,AML-M2,AML-M3,AML-M4,AML,AML-M4E0,35,薈萃醫(yī)學(xué),36,薈萃醫(yī)學(xué),37,薈萃醫(yī)學(xué),38,薈萃醫(yī)學(xué),Other new developed methods,39,薈萃醫(yī)學(xué),Differential Diagnosis,Pseudoleukem

19、ia,Myelodysplastic syndrome,Nonleukemic pancytopenia,40,薈萃醫(yī)學(xué),Treatment,Supportive cares and preparation of the patients Antileukemic therapy Therapy of the central nervous system Stem cell transplantation,41,薈萃醫(yī)學(xué),Anemia Hemorrhage Infection,42,薈萃醫(yī)學(xué),Hematological support Transfusion of Platelets Tran

20、sfusion of packed red cells Transfusions of granulocytes Transfusions of IgG,43,薈萃醫(yī)學(xué),Infection control Special precautions: protective isolation,Elimination of contaminated foods,Oral and digestive system care,Broad spectrum antibiotics,GM-CSF administration,44,薈萃醫(yī)學(xué),Antileukemic therapy,Chemotherapy

21、 to kill leukemia cells using strong anti-cancer drugs,45,薈萃醫(yī)學(xué),Treatment phases,Induction 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 hematopoiesis Post-remission therapy: to eliminate any leukemia cells pote

22、ntial hiding in the body,46,薈萃醫(yī)學(xué),Special subtypes,Acute promyelocytic Leukemia (APL): because of the small particles (procoagulants) inside the APL cell, DIC are commonly seen in this type of AML,47,薈萃醫(yī)學(xué),Normal,APL,Genes essential for differentiation are shut down by the fusion proteins PML-RARalpha

23、,48,薈萃醫(yī)學(xué),Differentiation agents (all-trans retinoic acid, arsenic trioxide),49,薈萃醫(yī)學(xué),Hyperleukecytosis: cause a batch of complications and should be treated using leukapheresis ( exchanging transfusion) or preinduction treatment prior to intensive chemotherapy,50,薈萃醫(yī)學(xué),Acute leukemia over 60 years of

24、age is less responsive to chemotherapy Standard two-drugs therapy can be used. CR 30% Intolerant to standard therapy. Low-dose of Ara-C can be used for 14-28 days,51,薈萃醫(yī)學(xué),Therapy of the CNS leukemia,The CNS is a frequent sanctuary site for leukemic cells because most of the chemotherapy drugs are no

25、t able to reach the CNS. Some types of acute leukemia have tendency to be with CNS leukemia such as AML (M4, M5), ALL,52,薈萃醫(yī)學(xué),Intrathecal chemotherapy,Cranial irradiation,53,薈萃醫(yī)學(xué),Stem cell transplantations,The main purpose of BMT and PBSCT in cancer treatment is to make it possible for patients to receive very