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

By Mohamed El Missiry, Henrik Hjorth-Hansen, Johan Richter, Ulla Olson-Stromberg, Leif Stenke, Kimmo Porkka, Anna Kreutzman and Satu Mustjoki

Abstract

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

Topics: CHRONIC-PHASE, STEM-CELLS, EUROPEAN-LEUKEMIANET, IMATINIB, CML, DASATINIB, NILOTINIB, RECOMMENDATIONS, HYDROXYUREA, MANAGEMENT, 3111 Biomedicine, CHRONIC-PHASE, STEM-CELLS, EUROPEAN-LEUKEMIANET, IMATINIB, CML, DASATINIB, NILOTINIB, RECOMMENDATIONS, HYDROXYUREA, MANAGEMENT, 3111 Biomedicine
Publisher: PUBLIC LIBRARY OF SCIENCE
Year: 2017
OAI identifier: oai:helda.helsinki.fi:10138/179373
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