title: Monosomy 13 in metaphase spreads is a predictor of poor long-term outcome after bortezomib plus dexamethasone treatment for relapsed/refractory multiple myeloma.
abstract: We retrospectively investigated the prognostic impact of high-risk cytogenetic abnormalities (CAs) on the outcome of treatment with bortezomib plus dexamethasone (BD) in 43 relapsed/refractory (Rel/Ref) multiple myeloma patients. Fluorescence in situ hybridization (FISH) analysis identified del(13q) in 25 patients, t(4;14) in 14, t(14;16) in 4, 1q21 abnormality in 12 and del(17p) in 2, while G-banding also detected chromosome 13 monosomy (-13) in metaphase spreads from 7 patients. Eighteen of 25 patients with FISH-detected chromosome 13 abnormalities also exhibited other abnormalities. Median observation period was 510 days, and median overall survival (OS) and progression-free survival (PFS) were 912 days and 162 days, respectively. Detection of del(13q), t(4;14), t(14;16) or 1q21 abnormalities by FISH and co-occurrence of chromosome 13 abnormality with other abnormalities were not associated with poorer outcomes. In contrast, detection of -13 by G-banding in metaphase spreads showed significant association with shorter OS, although the overall response rate and PFS were not inferior to those for patients without -13 detected by G-banding. BD therapy may be a potent weapon for overcoming most classical high-risk CAs, while the detection of -13 in metaphase spreads may serve as a predictor of highly progressive disease, even when treated with BD.
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Kiyota
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Shinichi
authors.initials: S
authors.lastname: Fuchida
authors.forename: Mio
authors.initials: M
authors.lastname: Yamamoto-Sugitani
authors.forename: Muneo
authors.initials: M
authors.lastname: Ohshiro
authors.forename: Yuji
authors.initials: Y
authors.lastname: Shimura
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Mizutani
authors.forename: Hisao
authors.initials: H
authors.lastname: Nagoshi
authors.forename: Nana
authors.initials: N
authors.lastname: Sasaki
authors.forename: Ryuko
authors.initials: R
authors.lastname: Nakayama
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Chinen
authors.forename: Natsumi
authors.initials: N
authors.lastname: Sakamoto
authors.forename: Hitoji
authors.initials: H
authors.lastname: Uchiyama
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Shigeo
authors.initials: S
authors.lastname: Horiike
authors.forename: Chihiro
authors.initials: C
authors.lastname: Shimazaki
authors.forename: Junya
authors.initials: J
authors.lastname: Kuroda
authors.forename: Masafumi
authors.initials: M
authors.lastname: Taniwaki
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D003907:Dexamethasone / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008677:Metaphase; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D011379:Prognosis; D011719:Pyrazines / Q000627:therapeutic use*; D012008:Recurrence; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D003907:Dexamethasone