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RESISTANCE TO IMATINIB1ry Resistance (Refractoriness):No CHR by 3 Mo ,No CCyR by 12 Mo orNo MMR @ 18 months, Bcr-Abl transcript rise or plateau2ry Resistance (acquired) :loss of an established Hematologic response (or progression to AP or ABC),loss of Cytogenetic response (increase of 30% or more Ph +ve BM metapahases @ 3 m’ intervals)or acquisition of CCA in Ph+ve cells orloss of Molecular response (rise of 1 log Bcr-Abl/Abl ratio % on serial testing)30consider : Abl Kinase domain mutations Study
ELN 2009: Prognostic factorsImatinib first lineAt any time: Predictors of lower PFS and OS:• CCA/Ph+ (chromosomal progression): Failure• Any loss of CHR or CCgR predicted shorter PFS/OS• The prognostic significance of loss of MMR iscontroversial; however, any rise in transcript levelswarrants closer monitoring.31Baccarani et al, J Clin Oncol., 2009
Page 1 and 2: CML MONITORING INTHE TKI ERAYasser
Page 3 and 4: 2008 WHO CLASSIFICATION OF MPNsPhil
Page 5 and 6: CML Phases5Chronic-phase CML (WHO):
Page 7 and 8: CML: Findings in PBMyelocyteBasophi
Page 9 and 10: Cytogenetic analysisKaryotype:Stand
Page 11 and 12: 11Philadelphia chromosome
Page 13 and 14: 13Iso (17)
Page 15 and 16: Fluorescent In Situ Hybridization(F
Page 17: 17Locations of the breakpoints in t
Page 20 and 21: 20RQ-PCR amplification assays:measu
Page 22 and 23: Use of a conversion factor to conve
Page 24 and 25: ELN 2009: Definitions of ResponseRe
Page 28 and 29: 28The BCR-ABL transcript percentpar
Page 33 and 34: 33Suboptimal response defined by RQ
Page 35 and 36: 13th Congress of the European He
Page 37 and 38: PFS100= 2 log reductions (n=59)
Page 39 and 40: BCR-ABL kinase domain mutations1. D
Page 41 and 42: Mutations critical for 2 nd generat
Page 43 and 44: ABL KINASE DOMAIN MUTATIONS IN IMAT
Page 45 and 46: Faster and deeper molecular respons
Page 47 and 48: Predictive Value of Pretreatment BC
Page 49: 49Thank you!

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