1、急性髓系白血病治疗最新进展,内容提要,治疗前评估诱导治疗最新进展诱导缓解后的治疗策略复发难治患者的治疗策略新药开发存在分子遗传学异常的AML治疗策略 （CBF及FLT3-ITD）,治疗前评估ASH推荐方案,Gary Schiller M.D. 55th ASH annual meeting,危险分层及预后,其他高危因素,MDS/MPN等血液病史高龄发病高白细胞男性LDH水平升高一般状况较差合并症常规诱导治疗后复发骨髓移植后复发巩固治理后短期内复发,Gary Schiller M.D. 55th ASH annual meeting,诱导治疗策略,诱导治疗策略,DNR 60mg/m2 VS 90
2、mg/m2,Induction Therapy For AML Patients With Daunorubicin Dose Of 60 Mg/m and 90 Mg/m Results In Similar Complete Response Rate, Relapse-Free and Overall Survival, Devillier et al. Blood，November 15, 2013 vol. 122,诱导治疗策略,High Dose Daunorubicin（90mg/m2） Vs Idarubicin（12mg/m2）,A Comparison Of Acute M
3、yelogenous Leukemia Induction Therapies: High Dose Daunorubicin Vs Idarubicin. Q. Ho, et al. Blood，November 15, 2013 vol. 122,诱导治疗策略,诱导治疗中的效果监测,记录患者诱导治疗过程中外周血d0-d7原始细胞所占比例与初发时比例当两者比值首次小于0.1时，记录其天数（外周血原始细胞下降log值大于1时天数）,发现D5是一个较为明显的节点 118名患者分为5d两组,Lacombe F, et al. Early clearance of peripheral blasts
4、 measured by flow cytometry during the first week of AML induction therapy as a new independent prognostic factor: a GOELAMS study. Leukemia. 2009;23(2):350-7.,诱导治疗中的效果监测,Gao Sujun, et al. The percentage of peripheral blood blasts on day 7 of induction chemotherapy predicts response to therapy and s
5、urvival in patients with acute myeloid leukemia. Chin Med J. 2014;127(2):290-3.,诱导治疗D7时，外周血原始细胞比例（D7PBBP），与CR率，OS及RFS均存在关系,D7PBBP Cut-off =0.43%,诱导缓解后的治疗策略,除了细胞生物学/分子遗传学指标危险度分级以外，微小残留病灶（MRD）在缓解后治疗的选择方面得到了广泛的认可和重视。,Hourigan CS, Karp JE. Minimal residual disease in acute myeloid leukaemia. Nature revi
6、ews Clinical oncology. 2013;10(8):460-71.,诱导缓解后的治疗策略,流式细胞学检测MRD水平累积复发率（CIR）在不同危险分组患者中的关系,Terwijn, et al. High Prognostic Impact of Flow Cytometric Minimal Residual Disease Detection in Acute Myeloid Leukemia: Data From the HOVON/SAKK AML 42A Study. Journal of clinical oncology : official journal of
7、the American Society of Clinical Oncology. 2013;31(31):3889-97.,诱导缓解后的治疗策略,2013 ASH Poster Sessions,骨髓MRD水平与预后的关系,MRD分组后不同治疗组的预后(5y-RFS),诱导缓解后的治疗策略,Vidriales,et al, Minimal Residual Diease Evaluation By Flow Cytometry Is a Complementary Tool To Cytogenetics For Treatment Decision In Acute Myeloid Le
8、ukemia, Blood，November 15, 2013 vol. 122,传统分子细胞学+MRD 积分系统,诱导缓解后的治疗策略,骨髓流式细胞学MRD水平,MRD（-）,MRD（+）,中危组,大剂量阿糖胞苷为基础的化疗或自体干细胞移植,异基因骨髓干细胞移植,MRD与传统预后分层相结合,高危组,低危组,分子生物学/细胞遗传学预后分层,CBF-AML,FLT3-ITD AML,诱导缓解后的治疗策略,化疗 VS 移植,HCT-CI Hematopoietic Cell Transplantation-Specific Comorbidity Index,Sorror, et al, Hema
9、topoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT, 2005 106: 2912-2919,诱导缓解后的治疗策略,化疗 VS 移植,Mawad, et al. Frequency of allogeneic hematopoietic cell transplantation among patients with high- or intermediate-risk acute myeloid leukemi
10、a in first complete remission. Journal of clinical oncology. 2013;31(31):3883-8.,诱导缓解后的治疗策略,化疗 VS 移植,Stelljes, et al. Allogeneic Transplantation Versus Chemotherapy as Postremission Therapy for Acute Myeloid Leukemia: A Prospective Matched Pairs Analysis. Journal of clinical oncology , 2013,NRM,CRI,
11、OS,RFS,诱导缓解后的治疗策略,化疗 VS 移植,Stelljes, et al. Allogeneic Transplantation Versus Chemotherapy as Postremission Therapy for Acute Myeloid Leukemia: A Prospective Matched Pairs Analysis. Journal of clinical oncology , 2013,复发难治患者的治疗策略,仍以临床试验为主要治疗方法，获得CR后尽快行骨髓移植,ASH oral and post sessionsclinical trials,复
12、发难治患者的治疗策略,最新临床试验结果,新药开发,Lancet JE. New agents: great expectations not realized. Best practice 26(3):269-74,新药开发,新药-去甲基药物,Navada SC, Steinmann J, Lubbert M, Silverman LR. Clinical development of demethylating agents in hematology. The Journal of clinical investigation. 2014;124(1):40-6.,新药-去甲基药物,Kan
13、tarjian, et al. Multicenter, Randomized, Open-Label, Phase III Trial of Decitabine Versus Patient Choice, With Physician Advice, of Either Supportive Care or Low-Dose Cytarabine for the Treatment of Older Patients With Newly Diagnosed Acute Myeloid Leukemia. Journal of Clinical Oncology. 2012;30(21)
14、:2670-7.,新药-核苷类似物,Gary Schiller M.D. 55th ASH annual meeting,新药-核苷类似物,Kantarjian H, Faderl S, Garcia-Manero G, Luger S, Venugopal P, Maness L, et al. Oral sapacitabine for the treatment of acute myeloid leukaemia in elderly patients: a randomised phase 2 study. The Lancet Oncology. 2012;13(11):1096-
15、104,CBF-AML,High-dose Cytarabine (HiDAC) Intensification Kit mutation in CBF-AMLRisk-directed treatment using MRD monitoring,CBF-AML HiDAC,Peter Paschka M.D. 55th ASH annual meeting,CBF-AML Kit mutation,Peter Paschka M.D. 55th ASH annual meeting,FLT3-ITD AML,High mutant ration = poor prognosis FLT3-
16、ITD allelic ratio0.8 = adverse riskAllogenetic transplant is the best choice in first remissionEven with allogeneic transplant, FLT3-ITD mutant still has a negative prognostic effect with increased relapse riskFLT3 inhibitors,FLT3 inhibitors,Mark Levis M.D. PhD 55th ASH annual meeting,FLT3 inhibitor
17、s-Quizartinib,Sexauer, et al. Terminal myeloid differentiation in vivo is induced by FLT3 inhibition in FLT3/ITD AML. Blood. 2012 120: 4205-4214,FLT3 inhibitors-Quizartinib,Quizartinib,Quizartinib in relapsed or refractory AML Phase I,Quizartinib,Quizartinib in relapsed or refractory AML Phase I,Cor
18、tes, et al. Phase I study of quizartinib administered daily to patients with relapsed or refractory acute myeloid leukemia irrespective of FMS-like tyrosine kinase 3-internal tandem duplication status. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2013;31(29):3681-7,FLT3 inhibitors,Smith, et al. Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia. Nature. 2012;485(7397):260-3,Thank You！,
