1、1Granulocytic leukemia 1.chronic myelocytic leukemia; CML 2.acute myeloblastic leukemia;AML21： Chronic myelocytic leukemia 3chronic myelocytic leukemia (CML)Malignant clonal hematopoietic stem cell disease White blood cell count Can see the various stages GranulocytesMainly in late stage Spleen sign

2、ificantly increasedEven splenomegaly More than 90% existsPh chromosomeAnd BCR / ABLFusion gene 【clinical manifestation 】4Staging of the International Bone Marrow Transplant Registry group of CMLIn phasesclinical manifestation chronic phase No obvious symptoms Accelerated phase or blast phase charact

3、eristics accelerated phase 1.Difficult to control the number of leukocytes in the conventional treatment 2.Leukocyte doubling time of less than 5 days 3.Bone marrow or blood the Central Plains granulocytes 10% 4.Granulocytes in bone marrow or blood Zhongyuan + promyelocytes 20% 5.Blood basophils + e

4、osinophils 20% 6.Anemia or thrombocytopenia not improve after conventional treatment 7.Persistent platelet count increased 8.Additional chromosomal abnormalities involving new clone 9.Spleen progressive enlargement 10.The chloroma occurred or bone marrow fibrosis acute transformation phase Granulocy

5、tes in bone marrow or blood Zhongyuan + promyelocytes 30% 5Chronic myelocytic leukemia chronic phaseThree phases accelerated phase acute transformation phase 6Chronic phase Early symptoms : occasionally found blood abnormalities , splenomegaly Hypermetabolism symptoms : fatigue, fever, sweating, nig

6、ht sweats , weight loss, etc. Bloating , splenomegaly , splenic infarction spleen pain 50% of liver mild to moderate swelling The following paragraph in the sternum tenderness positive Leukocyte stasis disease : respiratory distress , dizziness , neuropsychiatric symptoms , thrombosis 7Accelerated p

7、hase Unexplained fever, bone and joint pain , anemia , increased bleeding andProgressive enlargement of the spleen , the original treatment drugs ineffective 8Acute transformation phase CML end-stage , similar to the clinical manifestations of ALMostly anxious granulite , 20% -30 % of acute lymphoid

8、Occasional single nuclear megakaryocytes and red blood cells and other types of acute change .Prognosis is poor 91.hemogram White blood cell count WBC: count was significantly higher ，（10-200）109L，The neutrophils significantly increase , showing the various stages myeloid . Eosinophils, basophils （N

9、AP）Activity to reduce or negative Laboratory and laboratory examinations 10red blood count RBC：Normal or mildly reduced chronic phase , accelerated and blast phase blood platelet PLT：Chronic phase normal or，acute transformation phase11CML慢性期血象122.bone marrow ：chronic phase The marked hyperplasia To

10、hyperactivity Mainly myeloid , granulocyte / red significantly higher proportion of Neutral , the late promyelocytic rod leukocytes cells increased significantly in protomere10 Eosinophils, basophils increased Relative reduction of erythroid Normal or increased megakaryocytes reduce late Neutrophil

11、alkaline phosphatase (NAP) activity to reduce or negative effective treatmentWhen activity higher recurrence Shiyou decline Bone marrow biopsy : the degree of bone marrow fibrosis 13accelerated phase The original grain + promyelocytic values range between chronic phase and blast phase acute transfor

12、mation phase Original grain + promyelocytic3014CML慢性期骨髓象153.Cytogenetic and molecular biological changes More than 90% of patients with CML cells in Ph chromosome ( small on the 22ndChromosome ) , banding analysis for the t (9 ; 22 ) ( q34 ; q11 )RT-PCR examine ：BCR-ABL fusion gene（+）5CML BCRABLFusi

13、on gene positive ，PhChromosome negative 。Accelerated and blastic phase easy additional chromosome abnormalities 4.Blood biochemistry uric acid LDH antalzyme 16Ph染色體t(9;22)(q34;q11)17400bp200bp600bp500bp300bp100bp 90bp 165bp 2 1 M圖1 RT-PCR Bcr-abl融合基因電泳圖注：M：Marker; 1：b3a2；2：b2a2181. White blood cells

14、 continued to increase 2. hypersplenotrophy 3. A typical blood and Changes in bone marrow 4. NAP5.Phchromosome 6.BCR-ABLfusion geneDiagnosis and differential diagnosis Diagnostic basis 19Treatment chemotherapeutics Interferon Imatinib Allogeneic hematopoietic stem cell transplantation Chronic period

15、 biotherapy20 CMLEfficacy assessments Hematologic complete remission （HCR）： Return to normal blood , bone marrow Cytogenetic response Significant cytogenetic response （MCyR）： Bone marrow of Ph -positive cells 35Complete cytogenetic response（ CCyR): Bone marrow Ph -positive cells 0 Molecular remissio

16、n Complete molecular response （CMoR): BCR/ABL Complete molecular response Major molecular response（MMoR) BCR/ABL3log21(一）chemotherapy 1HydroxyureaPreferred chemotherapy drugs 2. Of busulfan ( Maryland )Alkylating agents , acting on early progenitor cells Only reach hematologic remission , does not c

17、hange the survival ( 40 months or so )3. indirubin 4. Low-dose cytarabine 22interferon （IFN-）（三）imatinib mesylate（二）biotherapy（四）bone marrow transplantation （五）Spleen radiation 23PPPADPPPPPPATPsignal transductionsubstrateeffector moleculeBcr-Abl signal transductionBcr-Abl24imatinib mesylate ：mechani

18、sm of actionPPPPATPSIGNALING 甲磺酸伊馬替尼Bcr-AblSavage and Antman. N Engl J Med. 2002;346:683.25Kantarjian H, Sawyers C, Hochhaus A, et al. N Engl J Med. 2002;346:645-652Talpaz M, Silver RT, Drucker BJ, et al. Blood. 2002;99:3530-3539Data on file. Novartis Pharma AG, Basel, Switzerland. 100806040200Significant cytogenetic response rate Complete cytogenetic response rate Early chronic Chronic late accelerated phaseBlastic phase Remission rate in p