Blood.
2007 Apr 15;109(8):3489-95. Epub 2007 Jan 5.
Genetic abnormalities and survival in
multiple myeloma: the experience of the Intergroupe
Francophone du Myélome.
Avet-Loiseau H, Attal M, Moreau P,
Charbonnel C, Garban F, Hulin C, Leyvraz S,
Michallet M, Yakoub-Agha I, Garderet L, Marit G,
Michaux L, Voillat L, Renaud M, Grosbois B, Guillerm
G, Benboubker L, Monconduit M, Thieblemont C,
Casassus P, Caillot D, Stoppa AM, Sotto JJ,
Wetterwald M, Dumontet C, Fuzibet JG, Azais I,
Dorvaux V, Zandecki M, Bataille R, Minvielle S,
Harousseau JL, Facon T, Mathiot C.
INSERM Unité 601, Laboratoire
d'Hématologie, Institut de Biologie, 9 quai Moncousu,
44093 Nantes, France. herve.avetloiseau@chu-nantes.fr
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.
PMID: 17209057 [PubMed - indexed for
MEDLINE]