title: Negative prognostic significance of two or more cytogenetic abnormalities in multiple myeloma patients treated with autologous stem cell transplantation.
abstract: Malignant plasma cells in multiple myeloma (MM) are frequently characterized by complex karyotypes and chromosome instability. These cytogenetic changes are considered important prognostic indicators in MM patients. We have studied samples from 68 patients with newly diagnosed MM who were treated with high-dose chemotherapy and autologous stem cell transplantation. G-banding revealed abnormal karyotypes in 14 of 55 patients (25%) who had informative conventional cytogenetics. The combination of cytoplasmic immunoglobulin light chain labeling and interphase fluorescent in situ hybridization (cIg-FISH) revealed the presence of genetic aberrations in 53 of 68 patients (78%). Chromosome 13 abnormalities were found in 33 patients (50%) and IgH rearrangements in 36 patients (56.25%). In IgH positive patients we performed subsequent examinations of IgH affecting translocations t(4;14) and t(11;14) and we found translocation t(11;14) in 8 patients (12.5%) and t(4;14) in 10 patients (15.5%). The occurrences of others chromosomal abnormalities with known prognostic impact in MM were as follows: del(17)(p13) was present in 5 patients (9.8%) and gain 1q21 in 14 patients (36%). Analysis of survival of patients with different cytogenetic abnormalities revealed shorter overall survival (OS) in patients with IgH rearrangements (p=0.020) and trend to shorter OS in patients with gain 1q21 (p=0.064), respectively. Remarkably, patients with two or more aberrations had significantly shorter overall survival (p=0.001), time to progression (p=0.036) and progression free survival (p=0.008). Our results show a high incidence of chromosomal abnormalities in MM patients and confirm the prognostic impact of selected chromosomal aberrations as well as cumulative effect of multiple cytogenetic changes occurring simultaneously.
authors.affiliation: University Research Centre - Czech Myeloma Group, Masaryk University, Brno, Czech Republic. kugl@sci.muni.cz
authors.forename: H
authors.initials: H
authors.lastname: Greslikova
authors.forename: R
authors.initials: R
authors.lastname: Zaoralova
authors.forename: H
authors.initials: H
authors.lastname: Filkova
authors.forename: P
authors.initials: P
authors.lastname: Nemec
authors.forename: A
authors.initials: A
authors.lastname: Oltova
authors.forename: R
authors.initials: R
authors.lastname: Kupska
authors.forename: P
authors.initials: P
authors.lastname: Rudolecka
authors.forename: J
authors.initials: J
authors.lastname: Smetana
authors.forename: L
authors.initials: L
authors.lastname: Pour
authors.forename: L
authors.initials: L
authors.lastname: Zahradova
authors.forename: M
authors.initials: M
authors.lastname: Krejci
authors.forename: T
authors.initials: T
authors.lastname: Buchler
authors.forename: Z
authors.initials: Z
authors.lastname: Adam
authors.forename: R
authors.initials: R
authors.lastname: Hajek
authors.forename: P
authors.initials: P
authors.lastname: Kuglik
mesh_terms: D000328:Adult; D000368:Aged; D002869:Chromosome Aberrations; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D020732:Cytogenetic Analysis; D005260:Female; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000235:genetics; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D009367:Neoplasm Staging; D011379:Prognosis; D033581:Stem Cell Transplantation; D015996:Survival Rate; D014178:Translocation, Genetic / Q000235:genetics; D014182:Transplantation, Autologous
chemical_list: D007147:Immunoglobulin Light Chains