CCONMDPSatelliteDevine分子分型骨髓移植学习教案

1、会计学1CCONMDPSatelliteDevine分子分型骨髓分子分型骨髓移植移植DisclaimerThe materials published on the Clinical Care Options Web site reflect the views of the authors of the CCO material, not those of Clinical Care Options, LLC, the CME providers, or the companies providing educational grants. The materials may discuss

2、 uses and dosages for therapeutic products that have not been approved by the United States Food and Drug Administration. A qualified healthcare professional should be consulted before using any therapeutic product discussed. Readers should verify all information and data before treating patients or

3、 using any therapies described in these materials.第1页/共49页第2页/共49页第3页/共49页FactorCommentAgeMajor impact at diagnosisWBCContinuous variablePrior therapy or MDS?Karyotype may be more importantExtramedullary diseaseVariableDay 14 blast countHigher percentage worse# cycles of inductionOne better than two

4、Cytogenetic/molecular profileMajor Impact at diagnosisGene expression profileCan further subdivide patientsMicroRNA expressionNeeds validation by other groupsGene sequencingFuture applicationMRD detection at CR?; seems like it should be useful第4页/共49页FactorCommentBasis for Transplant recommendation?

5、AgeMajor impact at diagnosisYesWBCContinuous variableNot solelyPrior therapy?Karyotype may be more importantNot solelyExtramedullary diseaseVariableNot solelyDay 14 blast countHigher percentage worseRarely# cycles of inductionOne better than twoRarelyCytogenetic/molecular profileMajor Impact at diag

6、nosisYesGene expression profileCan further subdivide patientsNot yetMicroRNA expressionNeeds validation by other groupsNot yetGene sequencingFuture applicationNot yetMRD detection at CR?; seems like it should be usefulPossibly for cytogenetics/FISH第5页/共49页Dhner K, et al. Haematologica 2008;93:976-98

7、2. Reproduced with permission. Major cytogenetic subgroups of acute myeloid leukemia (AML) (excluding acute promyelocytic leukemia) and associated gene mutations第6页/共49页Byrd JC, et al. Blood 2002;100:4325-4336. This research was originally published in Blood. 2002 the American Society of Hematology.

8、CALGB Database: Outcomes in AML Patients 60 years of Age based on Karyotype at Diagnosis第7页/共49页SWOG/ECOG TrialSlovak ML, et al. Blood 2000;96:4075-4083. This research was originally published in Blood. 2000 the American Society of Hematology.第8页/共49页EORTC-LG/GIMEMASuciu S, et al. Blood. 2003;102:12

9、32-1240. This research was originally published in Blood. 2003 the American Society of Hematology.第9页/共49页第10页/共49页第11页/共49页第12页/共49页Dhner H, et al. Blood. 2009 Oct 30. Epub ahead of print. This research was originally published in Blood. 2009 the American Society of Hematology.第13页/共49页Gene Mutatio

10、nPrognostic ImpactNPM1Favorable in absence of Flt3 ITDFlt3 ITD/allele ratioUnfavorableFlt3 TKDControversialCEBPAFavorableMLL PTDUnfavorableRasNeutralWT-1ControversialRunx1Unfavorable第14页/共49页GeneImpact of OverexpressionBAALC UnfavorableERGUnfavorableMN1UnfavorableMir181Favorable第15页/共49页Metzeler K H

11、, et al. J Clin Oncol. 2009;27:5031-5038. Reprinted with permission. 2009 American Society of Clinical Oncology. All rights reservedHigh expression of BAALC, ERG, or MN1 predicts shorter overall survival in cytogenetically normal acute myeloid leukemia第16页/共49页Genetic group SubsetsFavorable t(8;21)(

12、q22;q22); RUNX1-RUNX1T1inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11Mutated NPM1 without FLT3-ITD (normal karyotype)Mutated CEBPA (normal karyotype)Intermediate-I Mutated NPM1 and FLT3-ITD (normal karyotype)Wild type NPM1 and FLT3-ITD (normal karyotype)Wild type NPM1 without FLT3-ITD (normal

13、karyotype)Intermediate-II t(9;11)(p22;q23); MLLT3-MLLCytogenetic abnormalities not classified as favorable or adverseAdverse inv(3)(q21q26.2) or t(3;3)(q21;q26.2); RPN1-EVI1t(6;9)(p23;q34); DEK-NUP214t(v;11)(v;q23); MLL rearranged-5 or del(5q); -7; abnl(17p); complex karyotype; monosomal karyotypeDh

14、ner H, et al. Blood. 2009 Oct 30. Epub ahead of print This research was originally published in Blood. 2009 the American Society of Hematology.第17页/共49页Schlenk RF, et al. New Engl J Med. 2008;358:1909-1918. Reprinted with permission 2009 Massachusetts Medical Society.第18页/共49页Koreth J, et al. JAMA 2

15、009;301:2349-2361. Reproduced with permission.Overall Survival Benefit of Allogeneic SCT for AML in First Complete Remission第19页/共49页第20页/共49页nCytogenetically normalnDecision based on molecular risk?nShould all Flt3 ITD patients be allografted?第21页/共49页第22页/共49页第23页/共49页Schetelig J, et al. J Clin On

16、col. 2008;26:5183-5191. Reprinted with permission. 2008 American Society of Clinical Oncology. All rights reserved第24页/共49页Log-rank p-value 0.0001n=1735n=2621n=2184n=2234第25页/共49页第26页/共49页第27页/共49页第28页/共49页第29页/共49页Cooley S, et al. Blood 2009;113:726-732. This research was originally published in Bl

17、ood. 2009 the American Society of Hematology.Transplantation using donors with KIR B haplotypes improves overall survival第30页/共49页Ciceri F, et al. Blood 2008;112:3574-3581. This research was originally published in Blood. 2008 the American Society of Hematology.EBMT Analysis: Leukemia Free Survival

18、for AML Patients Receiving Haploidenitcal Transplantation according to disease stage第31页/共49页Gutman JA, et al. Biol Blood Marrow Transplant. 2009;15:1122-1129. Reproduced with permission.第32页/共49页第33页/共49页第34页/共49页Aversa F, et al. J Clin Oncol. 1999;17:1545-1550. Reprinted with permission. 1999 American Society of Clinical Oncology. A