title: Clinical value of assessing the response to imatinib monitored by interphase FISH and RQ-PCR for BCR-ABL in peripheral blood for long-term survival of chronic phase CML patients: results of the Niigata CML-multi-institutional co-operative clinical study.
abstract: This retrospective analysis investigated the prognostic value of monitoring the response to imatinib using peripheral blood (PB) samples and the impact of the response on outcome in 133 patients with chronic myeloid leukemia (CML). We divided the response into 3 categories according to the results of neutrophil (N)-FISH and BCR-ABL transcript levels in PB; more than a 3-log reduction [major molecular response (MMR)], between a 2-log and 3-log reduction or negative with N-FISH [complete cytogenetic response equivalent (CCyRe)], N-FISH positive or less than a 2-log reduction (non-CCyRe). The median follow-up was 5.46 years. At 5 years, the overall survival (OS) rate and progression-free survival (PFS) rate were 94.4 and 92.0%, respectively. The estimated rate of the CCyRe and MMR were 81.7 and 67.1%, respectively. 106 patients achieving the CCyRe had significantly better OS and PFS than 27 patients without achieving the CCyRe. Patients with MMR had significantly better survival free from death, progression, imatinib withdrawal and a loss of the CCyRe, than patients whose response level remained in the CCyRe without achieving MMR until 18 months. Our observation suggests that the response level of the CCyRe on PB serve as a prognostic indicator, and achieving MMR provides stable long-term survival.
authors.affiliation: Division of Bone Marrow Transplantation, Niigata University Medical and Dental Hospital, Asahimachi-dori 1-754, Chuoku, Niigata, 951-8520, Japan. tatsuof@med.niigata-u.ac.jp.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Furukawa
authors.affiliation: Laboratory of Hematology and Oncology, Graduate School of Health Sciences, Niigata University, Niigata, Japan.
authors.forename: Miwako
authors.initials: M
authors.lastname: Narita
authors.affiliation: Nagaoka Red Cross Hospital, Nagaoka, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Koike
authors.affiliation: Niigata City General Hospital, Niigata, Japan.
authors.forename: Kazue
authors.initials: K
authors.lastname: Takai
authors.affiliation: Niigata Prefectural Central Hospital, Joetsu, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Nagai
authors.affiliation: Nagaoka Chuo General Hospital, Nagaoka, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: Saiseikai Niigata Daini Hospital, Niigata, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Koyama
authors.affiliation: Niigata Prefectural Shibata Hospital, Shibata, Japan.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Seki
authors.affiliation: Niigata Prefectural Kamo Hospital, Kamo, Japan.
authors.forename: Hoyu
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Kariwagun General Hospital, Kashiwazaki, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fujiwara
authors.affiliation: Nagaoka Chuo General Hospital, Nagaoka, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kishi
authors.affiliation: Niigata City General Hospital, Niigata, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Nikkuni
authors.affiliation: Niigata Prefectural Central Hospital, Joetsu, Japan.
authors.forename: Noriatsu
authors.initials: N
authors.lastname: Isahai
authors.affiliation: Tsubame Rosai Hospital, Tsubame, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Higuchi
authors.affiliation: Niigata Medical Center, Niigata, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Nomoto
authors.affiliation: Niigata Minami Hospital, Niigata, Japan.
authors.forename: Souichi
authors.initials: S
authors.lastname: Maruyama
authors.affiliation: Division of Bone Marrow Transplantation, Niigata University Medical and Dental Hospital, Asahimachi-dori 1-754, Chuoku, Niigata, 951-8520, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Masuko
authors.affiliation: Division of Hematology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kuroha
authors.affiliation: Division of Hematology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Abe
authors.affiliation: Division of Hematology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Toba
authors.affiliation: Laboratory of Hematology and Oncology, Graduate School of Health Sciences, Niigata University, Niigata, Japan.
authors.forename: Masuhiro
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: Division of Hematology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Yoshifusa
authors.initials: Y
authors.lastname: Aizawa
authors.affiliation: Niigata Minami Hospital, Niigata, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Shibata
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D044466:Asian People; D001549:Benzamides; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate; D017404:In Situ Hybridization, Fluorescence; D007564:Japan; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic / Q000379:methods; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology; D010879:Piperazines / Q000008:administration & dosage*; D016133:Polymerase Chain Reaction; D011743:Pyrimidines / Q000008:administration & dosage*; D015996:Survival Rate; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl