microRNA-与急性粒细胞白血病课件.ppt

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1、Todd A FehnigerHematology Grand RoundMarch 13,2009Lenalidomide therapy for untreated acute myeloid leukemia in older adults(60 years of age)DisclosureClinical study funded in part by CelgeneNon-FDA approved use of Revlimid(lenalidomide)Case 71 yo M presented with dyspnea,fatigue,and pancytopeniaPerf

2、ormance status:ECOG 1PMH:HTN,GERD,BPHPE:petechiae,paleCBCWBC 1900/uL(ANC 190/uL)Hgb 6.7 g/dLPlts 74,000/uLfDifferential:33%blastsBlood 113:1002,2009Case Bone marrow biopsy and aspirate30%cellular90%myeloblastsFAB M0(undifferentiated)Flow:CD34+CD33+CD13+CD117+Routine cytogenetics:trisomy 1347,XY+135/

3、46,XY15FLT3ITD:PositiveBlood 113:1002,2009Acute Myeloid Leukemia in patients 60 year oldMedian age of AML is 65-7013,410 new AML cases/8,990 deaths in 200714.5/100,000 in adults 60 years0.7/100,00 in adults 60 yearsMajority of patients do not receive specific therapy(best supportive care)Median surv

4、ival 60 yo(prior MDS,therapy related,de novo all eligible)Exclude:5q-and favorable risk cytogeneticsCheson JCO 2007IWG Criteria for AML06-0907:Stage 1(Cohort 1)ResultsWHO IWG Criteria:(n=15 total patients)CRc:1(duration:9 months)PR:2(duration:6 and 12 months-ongoing)SD:4(duration:3,3,4,7 months)Trea

5、tment failure indeterminate cause:6Rash,Sepsis,Cardiac ArrestProgressive disease 2 cycles Len(n=3)Morphologic leukemia free BM at d15 w/PD at d30Treatment failure resistant disease:2Stage 2/Cohort 2 SchemaStage 2=Cohort 2N=27 patientsIndependent analysisPreliminary Results Cohort 2(n=25 so far)Unpub

6、lishedCase:Clinical Course Pt.007Case:Follow-upBM(%)020406080100Day 0 Day 15 Day 30 Day 75LDcycle 1BM blastsBM cellularityWBC countHemoglobin(g/dL)024681012Day 0Day 15 Day 30 Day 75LDcycle 1HemoglobinPlatelets02.04.06.08.010.0050100200250300Platelets(x103/L)WBC(x 103/L)150CR Aspirate 100XCR Leder 10

7、XCR Leder 100XLenalidomide has activity in AML how does it work?Modulation of NK cell responses?Correlative studies evaluating NK cells prior to,during,and after therapyDirect effects on AML?BM blasts at Dx:In vitro lenalidomide exposure,follow blast cell death compared to vehicle;correlation to res

8、ponse?Leukemia microenvironment?Flow for CXCR4 on AML blastsThis would be a great project for a fellow!AcknowledgmentsRavi VijAlissa NelsonKim TrinkausJackie PaytonBMT/leukemia physicians and team membersASCO FoundationSiteman Cancer CenterDisclosures:This study was funded in part by CelgeneNon-FDA approved(investigational)use of Revlimid(lenalidomide)No financial interest