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

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El Missiry , M , Hjorth-Hansen , H , Richter , J , Olson-Stromberg , U , Stenke , L , Porkka , K , Kreutzman , A & Mustjoki , S 2017 , ' Early BCR-ABL1 Transcript Decline after 1 Month of Tyrosine Kinase Inhibitor Therapy as an Indicator for Treatment Response in Chronic Myeloid Leukemia ' , PLoS One , vol. 12 , no. 1 , 0171041 . https://doi.org/10.1371/journal.pone.0171041

Title: Early BCR-ABL1 Transcript Decline after 1 Month of Tyrosine Kinase Inhibitor Therapy as an Indicator for Treatment Response in Chronic Myeloid Leukemia
Author: El Missiry, Mohamed; Hjorth-Hansen, Henrik; Richter, Johan; Olson-Stromberg, Ulla; Stenke, Leif; Porkka, Kimmo; Kreutzman, Anna; Mustjoki, Satu
Contributor: University of Helsinki, Department of Oncology
University of Helsinki, Clinicum
University of Helsinki, Medicum
Date: 2017-01-30
Language: eng
Number of pages: 17
Belongs to series: PLoS One
ISSN: 1932-6203
URI: http://hdl.handle.net/10138/179373
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.
Subject: CHRONIC-PHASE
STEM-CELLS
EUROPEAN-LEUKEMIANET
IMATINIB
CML
DASATINIB
NILOTINIB
RECOMMENDATIONS
HYDROXYUREA
MANAGEMENT
3111 Biomedicine
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