title: A prospective analysis of clinical efficacy and safety in chronic myeloid leukemia-chronic phase patients with imatinib resistance or intolerance as evaluated using European LeukemiaNet 2013 criteria.
abstract: BACKGROUND
  We conducted a phase II study to evaluate the efficacy and safety of dasatinib in Japanese patients with imatinib-resistant or imatinib-intolerant chronic myeloid leukemia (CML).
  
  
  METHODS
  From 2009 to 2011, 54 CML-chronic phase (CP) patients with resistance (n = 40) or intolerance (n = 25) to imatinib were registered to undergo dasatinib treatment. Eleven patients showed both resistance and intolerance to imatinib. Coincidentally, the resistance criteria in this study were the same as a non-optimal response to tyrosine kinase inhibitors (TKIs) as defined in the European LeukemiaNet (ELN) 2013 recommendations.
  
  
  RESULTS
  The overall incidence rate of major molecular response (MMR) at 12 months was 62.3% (n = 47). Forty patients with resistance to imatinib who were 'warning' and 'failure' patients based on the ELN 2013 recommendations were assessed; cumulative MMR and MR(4.5) rates were 62.5% (n = 39) and 21.0% (n = 40), respectively, at 12 months. Twelve patients who showed a BCR-ABL transcript level >1% on the international scale did not achieve a MMR or discontinued dasatinib treatment because of insufficient effects. With regard to safety issues, grade 3/4 non-hematologic adverse events (AEs) were infrequent.
  
  
  CONCLUSIONS
  Patients with non-optimal responses (who meet ELN 2013 warning and failure criteria) to imatinib should be switched quickly to dasatinib, which is less toxic in CML-CP patients, to improve their prognoses. A BCR-ABL1 IS of <1% at 3 months of dasatinib administration is a landmark for good therapeutic outcome.
authors.affiliation: Department of Hematology and Oncology, Iwate Medical University, Morioka, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Murai
authors.affiliation: Department of Hematology, Aomori Prefectural Central Hospital, Aomori, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Akagi
authors.affiliation: Department of Hematology, Iwate Prefectural Chubu Hospital, Kitakami, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Shimosegawa
authors.affiliation: Department of Hematology, Osaki Citizen Hospital, Osaki, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Sugawara
authors.affiliation: Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Ishizawa
authors.affiliation: Department of Hematology and Oncology, Iwate Medical University, Morioka, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Ito
authors.affiliation: Department of Hematology, Morioka Red Cross Hospital, Morioka, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Murai
authors.affiliation: Department of Internal Medicine, Omagari Kosei Medical Center, Omagari, Japan.
authors.forename: Mutsuhito
authors.initials: M
authors.lastname: Motegi
authors.affiliation: Department of Hematology, National Hospital Organization, Sendai Medical Center, Sendai, Japan.
authors.forename: Hisayuki
authors.initials: H
authors.lastname: Yokoyama
authors.affiliation: Department of Cardiology and Hematology, Fukushima Medical University, Fukushima, Japan.
authors.forename: Hideyoshi
authors.initials: H
authors.lastname: Noji
authors.affiliation: Department of Neurology, Hematology, Metabolism, Endocrinology, and Diabetology (DNHMED), Yamagata University Faculty of Medicine, Yamagata, Japan.
authors.forename: Katsushi
authors.initials: K
authors.lastname: Tajima
authors.affiliation: Department of Hematology, Yamagata City Hospital Saiseikan, Yamagata, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Kimura
authors.affiliation: Department of Internal Medicine, Niigata Cancer Center Hospital, Niigata, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Chou
authors.affiliation: Department of Cardiology and Hematology, Fukushima Medical University, Fukushima, Japan.
authors.forename: Kazuei
authors.initials: K
authors.lastname: Ogawa
authors.affiliation: Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Harigae
authors.affiliation: Department of Hematology, Aomori Prefectural Central Hospital, Aomori, Japan.
authors.forename: Kohmei
authors.initials: K
authors.lastname: Kubo
authors.affiliation: Department of Biostatistics, School of Public Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.|Interfaculty Initiative in Information Studies, The University of Tokyo, Tokyo, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Oba
authors.affiliation: Tokai Central Hospital, Kakamigahara, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Sakamoto
authors.affiliation: Department of Hematology and Oncology, Iwate Medical University, Morioka, Japan.
authors.forename: Yoji
authors.initials: Y
authors.lastname: Ishida
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D015466:Leukemia, Myeloid, Chronic-Phase / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl
keywords: European LeukemiaNet 2013 recommendations; chronic myeloid leukemia; dasatinib; major molecular response; molecular response ≧4.5 log reduction