新版本aml治療最新進(jìn)展

1、急性髓系白血病治療最新進(jìn)展,,內(nèi)容提要,治療前評(píng)估誘導(dǎo)治療最新進(jìn)展誘導(dǎo)緩解后的治療策略復(fù)發(fā)難治患者的治療策略新藥開(kāi)發(fā)存在分子遺傳學(xué)異常的AML治療策略 （CBF及FLT3-ITD）,治療前評(píng)估—ASH推薦方案,,Gary Schiller M.D. 55th ASH annual meeting,危險(xiǎn)分層及預(yù)后,其他高危因素,MDS/MPN等血液病史高齡發(fā)病高白細(xì)胞男性LDH水平升高一般狀況較差合

2、并癥常規(guī)誘導(dǎo)治療后復(fù)發(fā)骨髓移植后復(fù)發(fā)鞏固治理后短期內(nèi)復(fù)發(fā),Gary Schiller M.D. 55th ASH annual meeting,誘導(dǎo)治療策略,誘導(dǎo)治療策略,DNR 60mg/m2 VS 90mg/m2,Induction Therapy For AML Patients With Daunorubicin Dose Of 60 Mg/m² and 90 Mg/m² Results

3、In Similar Complete Response Rate, Relapse-Free and Overall Survival, Devillier et al. Blood，November 15, 2013 vol. 122,誘導(dǎo)治療策略,High Dose Daunorubicin（90mg/m2） Vs Idarubicin（12mg/m2）,A Comparison Of Acute Myelogenous Leuk

4、emia Induction Therapies: High Dose Daunorubicin Vs Idarubicin. Q. Ho, et al. Blood，November 15, 2013 vol. 122,誘導(dǎo)治療策略,誘導(dǎo)治療中的效果監(jiān)測(cè),記錄患者誘導(dǎo)治療過(guò)程中外周血d0-d7原始細(xì)胞所占比例與初發(fā)時(shí)比例當(dāng)兩者比值首次小于0.1時(shí)，記錄其天數(shù)（外周血原始細(xì)胞下降log值大于1時(shí)天數(shù)）,發(fā)現(xiàn)D5是一個(gè)較為明顯的節(jié)點(diǎn) 1

5、18名患者分為5d兩組,Lacombe F, et al. Early clearance of peripheral blasts 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):3

6、50-7.,誘導(dǎo)治療中的效果監(jiān)測(cè),Gao Sujun, et al. The percentage of peripheral blood blasts on day 7 of induction chemotherapy predicts response to therapy and survival in patients with acute myeloid leukemia. Chin Med J. 2014;127(2):2

7、90-3.,誘導(dǎo)治療D7時(shí)，外周血原始細(xì)胞比例（D7PBBP），與CR率，OS及RFS均存在關(guān)系,D7PBBP Cut-off =0.43%,誘導(dǎo)緩解后的治療策略,除了細(xì)胞生物學(xué)/分子遺傳學(xué)指標(biāo)危險(xiǎn)度分級(jí)以外，微小殘留病灶（MRD）在緩解后治療的選擇方面得到了廣泛的認(rèn)可和重視。,Hourigan CS, Karp JE. Minimal residual disease in acute myeloid leukaemia. Natur

8、e reviews Clinical oncology. 2013;10(8):460-71.,誘導(dǎo)緩解后的治療策略,流式細(xì)胞學(xué)檢測(cè)MRD水平累積復(fù)發(fā)率（CIR）在不同危險(xiǎn)分組患者中的關(guān)系,Terwijn, et al. High Prognostic Impact of Flow Cytometric Minimal Residual Disease Detection in Acute Myeloid Leukemia: Data

9、 From the HOVON/SAKK AML 42A Study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2013;31(31):3889-97.,誘導(dǎo)緩解后的治療策略,2013 ASH Poster Sessions,骨髓MRD水平與預(yù)后的關(guān)系,MRD分組后不同治療組的預(yù)后(5y-R

10、FS),誘導(dǎo)緩解后的治療策略,Vidriales,et al, Minimal Residual Diease Evaluation By Flow Cytometry Is a Complementary Tool To Cytogenetics For Treatment Decision In Acute Myeloid Leukemia, Blood，November 15, 2013 vol. 122,傳統(tǒng)分子細(xì)胞學(xué)+MRD

11、積分系統(tǒng),誘導(dǎo)緩解后的治療策略,骨髓流式細(xì)胞學(xué)MRD水平,MRD（-）,MRD（+）,中危組,大劑量阿糖胞苷為基礎(chǔ)的化療或自體干細(xì)胞移植,異基因骨髓干細(xì)胞移植,MRD與傳統(tǒng)預(yù)后分層相結(jié)合,高危組,低危組,分子生物學(xué)/細(xì)胞遺傳學(xué)預(yù)后分層,●CBF-AML,●FLT3-ITD AML,誘導(dǎo)緩解后的治療策略,化療 VS 移植,HCT-CI Hematopoietic Cell Transplantation-Specific Comor

12、bidity Index,Sorror, et al, Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT, 2005 106: 2912-2919,誘導(dǎo)緩解后的治療策略,化療 VS 移植,Mawad, et al. Frequency of al

13、logeneic hematopoietic cell transplantation among patients with high- or intermediate-risk acute myeloid leukemia in first complete remission. Journal of clinical oncology. 2013;31(31):3883-8.,誘導(dǎo)緩解后的治療策略,化療 VS 移植,Stellj

14、es, 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,OS,RFS,誘導(dǎo)緩解后的治療策略,化療 VS 移植,

15、Stelljes, et al. Allogeneic Transplantation Versus Chemotherapy as Postremission Therapy for Acute Myeloid Leukemia: A Prospective Matched Pairs Analysis. Journal of clinical oncology , 2013,復(fù)發(fā)難治患者的治療策略,仍以臨床試驗(yàn)為主要治療方法，獲得C

16、R后盡快行骨髓移植,ASH oral and post sessions——clinical trials,復(fù)發(fā)難治患者的治療策略,最新臨床試驗(yàn)結(jié)果,新藥開(kāi)發(fā),Lancet JE. New agents: great expectations not realized. Best practice & research Clinical haematology. 2013;26(3):269-74,新藥開(kāi)發(fā),新藥-去甲基藥物,N

17、avada SC, Steinmann J, Lubbert M, Silverman LR. Clinical development of demethylating agents in hematology. The Journal of clinical investigation. 2014;124(1):40-6.,新藥-去甲基藥物,,Kantarjian, et al. Multicenter, Randomized, O

18、pen-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. Jou

19、rnal of Clinical Oncology. 2012;30(21):2670-7.,新藥-核苷類似物,Gary Schiller M.D. 55th ASH annual meeting,新藥-核苷類似物,Kantarjian H, Faderl S, Garcia-Manero G, Luger S, Venugopal P, Maness L, et al. Oral sapacitabine for the t

20、reatment of acute myeloid leukaemia in elderly patients: a randomised phase 2 study. The Lancet Oncology. 2012;13(11):1096-104,CBF-AML,High-dose Cytarabine (HiDAC) Intensification Kit mutation in CBF-AMLRisk-direct

21、ed 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 FLT

22、3-ITD allelic ratio≥0.8 = 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 risk

23、FLT3 inhibitors,FLT3 inhibitors,Mark Levis M.D. PhD 55th ASH annual meeting,FLT3 inhibitors-Quizartinib,Sexauer, et al. Terminal myeloid differentiation in vivo is induced by FLT3 inhibition in FLT3/ITD AML. Blood.

24、 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,Cortes, et al. Phase I study of quizartinib adm

25、inistered 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 America