title: Biological and prognostic significance of interphase fluorescence in situ hybridization detection of chromosome 13 abnormalities (delta13) in multiple myeloma: an eastern cooperative oncology group study.
abstract: Chromosome 13 abnormalities (Delta13) have been associated with an unfavorable prognosis in patients with multiple myeloma (MM). The significance of this has been unresolved because of diverse methods of detection and heterogeneous groups of patients. We conducted a study of Delta13 in patients entered into the Eastern Cooperative Oncology Group trial E9486/E9487. Patients with newly diagnosed MM (median follow-up of survivors >100 months) were studied for Delta13, using bone marrow samples obtained at study enrollment. We used interphase fluorescence in situ hybridization with the probes LSI13 (Rb)/D13S319 with simultaneous immunofluorescence detection of bone marrow plasma cells (PCs). We detected Delta13 in 176 of 325 (54%) evaluable patients. Patients with Delta13 were more likely to have a serum monoclonal protein at a concentration < or =1 g/dl (22 versus 13%; P = 0.04), light-chain-only MM (19.3 versus 10.8%; P = 0.04), gamma light chain (42 versus 28%; P = 0.027), stage III (56 versus 42%; P = 0.014), and be female (60 versus 50%; P = 0.087). The PC labeling index and Delta13 correlated (P = 0.03). Patients with Delta13 were less likely to respond to treatment (74 versus 63%; P = 0.041) and had a significantly shorter median overall survival (34.9 versus 51 months; P = 0.021). The association of Delta13 and survival remained an independent prognostic variable in a regression model. Among patients with Delta13, those receiving IFN had a worse overall survival that those not receiving the medication (P = 0.03). The presence of Delta13 is an important and independent adverse prognostic factor in newly diagnosed MM and is associated with specific biological features.
authors.affiliation: Department of Hematology and Internal Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: Rafael
authors.initials: R
authors.lastname: Fonseca
authors.forename: David
authors.initials: D
authors.lastname: Harrington
authors.forename: Martin M
authors.initials: MM
authors.lastname: Oken
authors.forename: Gordon W
authors.initials: GW
authors.lastname: Dewald
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Bailey
authors.forename: Scott A
authors.initials: SA
authors.lastname: Van Wier
authors.forename: Kimberly J
authors.initials: KJ
authors.lastname: Henderson
authors.forename: Emily A
authors.initials: EA
authors.lastname: Blood
authors.forename: S Vincent
authors.initials: SV
authors.lastname: Rajkumar
authors.forename: Neil E
authors.initials: NE
authors.lastname: Kay
authors.forename: Brian
authors.initials: B
authors.lastname: Van Ness
authors.forename: Philip R
authors.initials: PR
authors.lastname: Greipp
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001854:Bone Marrow Cells / Q000473:pathology; D002869:Chromosome Aberrations; D002882:Chromosomes, Human, Pair 13; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007399:Interphase / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000098:blood supply / Q000235:genetics* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000473:pathology; D010950:Plasma Cells / Q000473:pathology; D011379:Prognosis; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D001613:beta 2-Microglobulin / Q000378:metabolism
chemical_list: D001613:beta 2-Microglobulin