title: Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myélome.
abstract: Acquired genomic aberrations have been shown to significantly impact survival in several hematologic malignancies. We analyzed the prognostic value of the most frequent chromosomal changes in a large series of patients with newly diagnosed symptomatic myeloma prospectively enrolled in homogeneous therapeutic trials. All the 1064 patients enrolled in the IFM99 trials conducted by the Intergroupe Francophone du Myélome benefited from an interphase fluorescence in situ hybridization analysis performed on purified bone marrow plasma cells. They were systematically screened for the following genomic aberrations: del(13), t(11;14), t(4;14), hyperdiploidy, MYC translocations, and del(17p). Chromosomal changes were observed in 90% of the patients. The del(13), t(11;14), t(4;14), hyperdiploidy, MYC translocations, and del(17p) were present in 48%, 21%, 14%, 39%, 13%, and 11% of the patients, respectively. After a median follow-up of 41 months, univariate statistical analyses revealed that del(13), t(4;14), nonhyperdiploidy, and del(17p) negatively impacted both the event-free survival and the overall survival, whereas t(11;14) and MYC translocations did not influence the prognosis. Multivariate analyses on 513 patients annotated for all the parameters showed that only t(4;14) and del(17p) retained prognostic value for both the event-free and overall survivals. When compared with the currently used International Staging System, this prognostic model compares favorably. In myeloma, the genomic aberrations t(4;14) and del(17p), together with beta2-microglobulin level, are important independent predictors of survival. These findings have implications for the design of risk-adapted treatment strategies.
authors.affiliation: INSERM Unité 601, Laboratoire d'Hématologie, Institut de Biologie, 9 quai Moncousu, 44093 Nantes, France. herve.avetloiseau@chu-nantes.fr
authors.forename: Hervé
authors.initials: H
authors.lastname: Avet-Loiseau
authors.forename: Michel
authors.initials: M
authors.lastname: Attal
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreau
authors.forename: Catherine
authors.initials: C
authors.lastname: Charbonnel
authors.forename: Frédéric
authors.initials: F
authors.lastname: Garban
authors.forename: Cyrille
authors.initials: C
authors.lastname: Hulin
authors.forename: Serge
authors.initials: S
authors.lastname: Leyvraz
authors.forename: Mauricette
authors.initials: M
authors.lastname: Michallet
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Yakoub-Agha
authors.forename: Laurent
authors.initials: L
authors.lastname: Garderet
authors.forename: Gérald
authors.initials: G
authors.lastname: Marit
authors.forename: Lucienne
authors.initials: L
authors.lastname: Michaux
authors.forename: Laurent
authors.initials: L
authors.lastname: Voillat
authors.forename: Marc
authors.initials: M
authors.lastname: Renaud
authors.forename: Bernard
authors.initials: B
authors.lastname: Grosbois
authors.forename: Gaelle
authors.initials: G
authors.lastname: Guillerm
authors.forename: Lotfi
authors.initials: L
authors.lastname: Benboubker
authors.forename: Mathieu
authors.initials: M
authors.lastname: Monconduit
authors.forename: Catherine
authors.initials: C
authors.lastname: Thieblemont
authors.forename: Philippe
authors.initials: P
authors.lastname: Casassus
authors.forename: Denis
authors.initials: D
authors.lastname: Caillot
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Stoppa
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Sotto
authors.forename: Marc
authors.initials: M
authors.lastname: Wetterwald
authors.forename: Charles
authors.initials: C
authors.lastname: Dumontet
authors.forename: Jean-Gabriel
authors.initials: JG
authors.lastname: Fuzibet
authors.forename: Isabelle
authors.initials: I
authors.lastname: Azais
authors.forename: Véronique
authors.initials: V
authors.lastname: Dorvaux
authors.forename: Marc
authors.initials: M
authors.lastname: Zandecki
authors.forename: Régis
authors.initials: R
authors.lastname: Bataille
authors.forename: Stéphane
authors.initials: S
authors.lastname: Minvielle
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Harousseau
authors.forename: Thierry
authors.initials: T
authors.lastname: Facon
authors.forename: Claire
authors.initials: C
authors.lastname: Mathiot
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D005602:France; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009101:Multiple Myeloma / Q000235:genetics* / Q000401:mortality*; D009367:Neoplasm Staging; D011446:Prospective Studies; D015996:Survival Rate