白血病双语

Leukemia,Department of hematology, Union Hospital Affiliated to Fujian Medical University.Fujian Institute of HematologyHuang Meijuan (黄美娟),I. Definition,Leukemia is a malignant blood disorder which is the results of the tumor proliferation of hematopoietic stem cells.,II. Classification,Acute non-lymphoblastic leukemia(ANLL),Leukemia,Acute leukemia,Chronic leukemia,Acute lymphoblastic leukemia (ALL),Chronic myeloid leukemia (CML),Chronic lymphoblastic leukemia(CLL),Incidence of leukemia,.Epidemiology and Etiology,.Epidemiology and Etiology,AML,Exposure to a variety of environmental agents, most likely due to links between exposure history and cytogenetic abnormalities.,Radiation,Benzene inhalation,Alcohol use,Smoking,Dyes,Herbicide(除草剂）,Pesticide（杀虫剂）,地沟油？,2 main types of therapy-related AML.,Therapeutic radiation also increases AML risk, particularly if given with alkylating agents such as cyclophosphamide, melphalan, and nitrogen mustard.,1. The “classic” type a latency period of 5-7 years,chromosomes 5 and/or 7,rearrangements at chromosome 11q23,Drugs, such as chloramphenicol（氯霉素）, phenylbutazone（苯基丁氮酮）, chloroquine, and methoxypsoralen, can induce marrow damage that may later evolve into AML.,2. inhibit the DNA repair enzyme topoisomerase II ：etoposide ，teniposide, usually 1-3 years,.Epidemiology and Etiology,AML,3. Infectious etiologies Human T-cell lymphotropic virus-1 adult T-cell leukemia/lymphoma. Epstein-Barr virus lymphoproliferative disorders (Burkitts lymphoma ,mature B-cell ALL),Unknown,1. Chromosomal translocations during fetal hematopoiesis,2. Postnatal genetic events are secondary contributors,.Epidemiology and Etiology,ALL,CML,CLL,？,.Epidemiology and Etiology,Acute leukemia,Concept of acute leukemia,Acute leukemia is the result of a malignant event occurring in an early hematopoietic precursor. Instead of proliferating and differentiating normally, the affected cell gives rise to progeny that fail to differentiate but continue to proliferate in an uncontrolled fashion.,Age-related incidence,I. Classification,（I）FAB,（I）FAB,（I）FAB,(II) WHO classification of AL 2008,Blood.2009,114:937-951,Blood.2009,114:937-951,(II) WHO classification of AL 2008,1. Anemia: fatigue, pale, ,2. Bleeding: Plt bruising. Disseminated intravascular coagulopathy (DIC),3. Fever: 38.5 infection.,II. Clinical manifestation,4. Infiltration of organ and tissues1). Lymphadenopathy and hepatosplenomegaly: rarely symptomatic, 60- 70% - T and mature B-cell ALL. minor or middle splenomegaly, rare huge splenomegaly2).Bone and joints ：tenderness, pain in joint -ALL3).Eyes： Chloromas and myeloblastomas- M0,M1,M24).Mouth and skin：infiltration of gingivae and skin- M4,M55).Central Nervous System (CNS-L): headache, vomit,coma-ALL6).Lung, Kidney，testicles,II. Clinical manifestation,III. Laboratory manifestation,1Peripheral blood countsAnemiaThrombocytopenia 25% WBC50x109/L; 25% WBC30%。又分三种亚型：粗颗粒型(M3a),M3b (早幼粒细胞细颗粒型),细颗粒型(M3b),变异型（M3v）,M3v (早幼粒细胞细颗粒型),M4(粒-单细胞型),BM中NEC的原始细胞30%原粒及以下各阶段粒细胞占3079%各阶段单核细胞20%和/或外周血原粒细胞35109/L。,M4E0 (粒-单细胞变异型),嗜酸粒细胞NEC的5%，且胞浆中同时出现嗜硷性颗粒，和/或不伴嗜酸性粒细胞。染色体畸形(ivt 16)。,M5(单核细胞型),M5a(原始单核细胞型):BM中原始细胞80%M5b: BM中原始细胞80%。,M6（急性红白血病）,骨髓中幼红细胞50%，非红系细胞中原始细胞（I型+II型）30%骨髓原红细胞胞体巨大，易见多个核和核分裂相,M7（急性巨核细胞白血病）,原始巨核细胞30%原始细胞增多，核呈圆形、深蓝，胞浆呈伪足状,L1,胞体小，较一致；胞浆少；核形规则、核仁小而不清楚，少见或不见。,L2,胞体大，不均一；胞浆常较多；核形不规则，常呈凹陷、折叠，核形规则，核仁清楚，一个或多个,L3,胞体大，均一；胞浆多，深兰色，有较多空泡，呈蜂窝状；核形规则，核仁清楚，一个或多个。,3. Histochemistry,4.ImmunologicPhenotypesofAL,Immunologic Subtypes of AML,5Cytogenetic and genic features,6PlasmaChemicalFindings,1) Increasesinserumuricacidand lacticdehydrogenaselevels2) Hypercalcemia3) Prolonged of PT、APTT，hypofibrinogenemia,IV. Diagnosis,1.Clinical manifestation2.Peripheral blood counts3.Marrow film,V. differencial diagnosis,1Aplastic anemia 2Myelodysplastic syndromes3Leukemoid reactions to infections4Infectious mononucleosis,（I）Supportive care （II）Chemotherapy （III）TherapyoftheCNS-L （IV） Therapyofthetesticles （V）StemCellTransplantation,VI. Treatment,（I）Supportive care,1Infection control 2Hematologic support 3Metabolic complications 4Hyperleukocytosis5. Psychosocialsupport,（II）Chemotherapy,The goal of initial chemotherapy is to induce a CR (complete remission) with restoration of normal marrow function.,1Treatment of ALL,Combination chemotherapy Three phases: A. remission induction VDLP, Hyper-CVAD et al. B. postremission therapy consolidation and maintenance chemotherapy. C. CNS prophylaxis intrathecal MTX radiation high-dose MTX or high-dose Ara-c,2Treatment of AML,A. Remission inductionD3A7 regimen (CR rate: 60-80%)DNR 45-60mg/m2/day for 3 days or IDA 8-12mg/m2/day for 3 daysAra-c 100-200mg/m2/day for 7daysB. Postremission therapy High-dose Ara-c (1.0-3.0/m2 q12h for 3-6 days) or HSCT,3. Treatment of APL(M3),A. all-trans-retinoic acid (ATRA)B. Arsenic trioxideC. Combination of ATRA and anthracycline ATRA+ Arsenic trioxideSide effect: differenciation syndromes,A. Long-term survival rates of only 5 to 10%B. Healthy older individuals should be offered standard chemotherapyC. Other patients for supportive care only or for alternative therapies currently under study,4. Treatment of AML in older patients,（III）Treatment of CNS-L,1Radiation 2IT: MTX + ARA-C + hydrocortisone3High-dose MTX, intensiveasparaginase, dexamethasone.,（IV）Treatmentofthetesticles,Radiation (Total dose 2000cGy);Both sides.,(V) Hematopoieticstemcelltransplantation（HSCT）,1. Autologous HSCT2. Allogeneic HSCT HistocompatibleDonors-HLA typing Conditioning regimen Engraftment, rejection Graft versus leukemia (GVL) or tumor (GVT) Graft versus host disease (GVHD),VII. Prognosis,Chronic myeloid leukemia(CML),I. Definition of CML,1. a clonal myeloproliferative disorder of the primitive hematopoietic stem cell that is characterized by overproduction of cells of the myeloid series, which results in marked splenomegaly and leukocytosis.2. Philadelphia (Ph) chromosome, t(9;22) (q34;q11.2). BCR-ABL fusion gene,Age-related incidence,II. MolecularPathology,MUTATIONOFABLANDBCRGENES,III. Clinical manifestations and laboratory findings,1. Common findings: fatigue, anemia, abdominal discomfort, splenomegaly, leukocytosis 2. 30% to 50% of patients asymptomatic at diagnosis 3. White blood cell count usually greater than 50 109 /L, with a left-shifted differential, basophilia, thrombocytosis,Definitions of the accelerated and blastic phased of CML,IV. Diagnosis,1. History and physical examination, complete blood count with differential and platelet count 2. Bone marrow aspiration and biopsy 3. Testing for the Ph chromosome by cytogenetic analysis or for the BCR-ABL fusion gene by FISH or by RT-PCR,V. Differential Diagnosis,1. Chronic myelomonocytic leukemia 2. Other myeloproliferative disorders 3. Leukemoid reactions,VI. Therapy,1. Imatinibmesylate 2. New tyrosine kinase inhibitors (dasatinib, nilotinib, bosutinib)3. Allogeneic stem cell transplantation4. Interferon-5. Other chemotherapeutic agents Hydroxyurea, Cytarabine, Homoharringtonine.,VI. Therapy,1. imatinib mesylate, IM. Glivec Targeted therapy Dose：CP 400mg qd AP 600mg qd BP/BC 800mg qd,VI. Therapy,2. Allo-SCT,2. Allo-SCT,3. Interferon-4. Other chemotherapeutic agents Hydroxyurea, Cytarabine, Homoharringtonine.,VI. Therapy,VII、Prognosis,Chronic lymphocytic leukemia (CLL),I. Definition of CLL,1.aneoplasticdiseasecharacterizedby the accumulationofsmall,mature, appearing lymphocytesintheblood,marrow, and lymphoidtissues. 2. Epidemiology 2.7 persons/100,000 in USA 0.05 persons/100,000 in China,II. Clinical manifestations,1. Most patients with CLL are asymptomatic2. fatigue, lethargy, loss of appetite, weight loss, and reduce