Early BCR-ABL1 Transcript Decline after 1 Month of Tyrosine Kinase Inhibitor Therapy as an Indicator for Treatment Response in Chronic Myeloid LeukemiaReport as inadecuate




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In chronic myeloid leukemia CML, early treatment prediction is important to identify patients with inferior overall outcomes. We examined the feasibility of using reductions in BCR-ABL1 transcript levels after 1 month of tyrosine kinase inhibitor TKI treatment to predict therapy response. Fifty-two first-line TKI-treated CML patients were included imatinib n = 26, dasatinib n = 21, nilotinib n = 5, and BCR-ABL1 transcript levels were measured at diagnosis dg and 1, 3, 6, 12, 18, 24, and 36 months. The fold change of the BCR-ABL1 transcripts at 1 month compared to initial BCR-ABL1 transcript levels was used to indicate early therapy response. In our cohort, 21% of patients had no decrease in BCR-ABL1 transcript levels after 1 month and were classified as poor responders. Surprisingly, these patients had lower BCR-ABL1 transcript levels at dg compared to responders 31% vs. 48%, p = 0.0083. Poor responders also significantly more often had enlarged spleen 55% vs. 15%; p<0.01 and a higher percentage of Ph+ CD34+CD38- cells in the bone marrow 91% vs. 75%, p<0.05. The major molecular response rates were inferior in the poor responders at 12m 18% vs. 64%, p<0.01; 18m 27% vs. 75%, p<0.01; 24m 55% vs. 87%, p<0.01. In conclusion, early treatment response analysis defines a biologically distinct patient subgroup with inferior long-term outcomes.



Author: Mohamed El Missiry, Henrik Hjorth-Hansen, Johan Richter, Ulla Olson-Strömberg, Leif Stenke, Kimmo Porkka, Anna Kreutzman, Satu M

Source: http://plos.srce.hr/



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