Blood Malignancies and Treatment

Biography

Biography: Mukul Gharote

Abstract

ASO-PCR is very rapid, cheap and sensitive technique for detection of KD mutations M351T, F317L, and F311C ABL mutation and is more sensitive than mutation detection by sequencing. Introduction: BCR-ABL Kinase domain mutations represent the most important disease-related factor in CML resistance. Highly resistant clones may preexist and emerge rapidly. ASO-PCR has high sensitivity in detecting pre-existing mutation, which in our retrospective analysis seems true, although ours was a retrospective analysis. Material & Method: Retrospective analysis of 50 patients of Imatinib resistance was done in GCRI, from January 2014 till may 2014. Response to Imatinib was defined according to European leukaemia net 2009 (ELN) criteria. Allelle Specific Oligonucleotide –Polymerase Chain Reaction (ASO-PCR) was performed on Genomic DNA, extracted from peripheral blood mononuclear cells (PBMCs).Results: Average age was 40.75years ,33 were males and 17 females. 47( 94%) were in Chronic phase, 2(4%) in accelerated phase, 1 (2%) in blastic crisis. 29/50 were having low EUTOS score , whereas SOKAl score was low in 20, intermediate in 21 while only 9 had high SOKAL at presentation. Median duration of Imatinib was 48 months. 43/50 had one or more than 1 mutation. T315I mutation in 5 (10%) patients. M351T in 32% (16/50) , F311L.in 8. Conclusion: Clinical correlates, speculate , that these mutation were pre-existing and were selected by standard dose Imatinib continued for median 4 years, detection of pre-exisiting mutation is not the current recommendation. We report low cytogenetic response (25%) and durability of response to 600 mg of Imatinib, even in M351T mutation, after 400 mg of Imatinib for median period of 2 years.