title: Early BCR-ABL1 Transcript Decline after 1 Month of Tyrosine Kinase Inhibitor Therapy as an Indicator for Treatment Response in Chronic Myeloid Leukemia.
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.
authors.affiliation: Hematology Research Unit Helsinki, Department of Hematology, University of Helsinki and Helsinki University Central Hospital Comprehensive Cancer Center, Helsinki, Finland.
authors.forename: Mohamed
authors.identifier: http://orcid.org/0000-0002-0816-8241
authors.initials: M
authors.lastname: El Missiry
authors.affiliation: Department of Hematology, St Olavs Hospital, Trondheim, Norway.|Department of Cancer Research and Molecular Medicine, St Olavs Hospital, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
authors.forename: Henrik
authors.initials: H
authors.lastname: Hjorth-Hansen
authors.affiliation: Department of Hematology and Vascular Disorders, Skåne University Hospital, Lund, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Richter
authors.affiliation: Department of Hematology, Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Ulla
authors.initials: U
authors.lastname: Olson-Strömberg
authors.affiliation: Department of Hematology, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.
authors.forename: Leif
authors.initials: L
authors.lastname: Stenke
authors.affiliation: Hematology Research Unit Helsinki, Department of Hematology, University of Helsinki and Helsinki University Central Hospital Comprehensive Cancer Center, Helsinki, Finland.
authors.forename: Kimmo
authors.initials: K
authors.lastname: Porkka
authors.affiliation: Hematology Research Unit Helsinki, Department of Hematology, University of Helsinki and Helsinki University Central Hospital Comprehensive Cancer Center, Helsinki, Finland.
authors.forename: Anna
authors.initials: A
authors.lastname: Kreutzman
authors.affiliation: Hematology Research Unit Helsinki, Department of Hematology, University of Helsinki and Helsinki University Central Hospital Comprehensive Cancer Center, Helsinki, Finland.|Department of Clinical Chemistry, University of Helsinki, Helsinki, Finland.
authors.forename: Satu
authors.initials: S
authors.lastname: Mustjoki
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D016044:Fusion Proteins, bcr-abl / Q000235:genetics* / Q000378:metabolism; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015703:Antigens, CD; D006454:Hemoglobins; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D016044:Fusion Proteins, bcr-abl