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. 2015 Dec 17;126(25):2713-9.
doi: 10.1182/blood-2015-06-650242. Epub 2015 Oct 29.

Understanding the role of hyperdiploidy in myeloma prognosis: which trisomies really matter?

Marie-Lorraine Chretien  1 , Jill Corre  2 , Valerie Lauwers-Cances  3 , Florence Magrangeas  4 , Alice Cleynen  2 , Edwige Yon  3 , Cyrille Hulin  5 , Xavier Leleu  6 , Frederique Orsini-Piocelle  7 , Jean-Sebastien Blade  5 , Claudine Sohn  8 , Lionel Karlin  9 , Xavier Delbrel  10 , Benjamin Hebraud  11 , Murielle Roussel  11 , Gerald Marit  12 , Laurent Garderet  13 , Mohamad Mohty  13 , Philippe Rodon  14 , Laurent Voillat  15 , Bruno Royer  16 , Arnaud Jaccard  17 , Karim Belhadj  18 , Jean Fontan  19 , Denis Caillot  1 , Anne-Marie Stoppa  20 , Michel Attal  11 , Thierry Facon  6 , Philippe Moreau  21 , Stephane Minvielle  4 , Hervé Avet-Loiseau  2
Affiliations

Understanding the role of hyperdiploidy in myeloma prognosis: which trisomies really matter?

Marie-Lorraine Chretien et al. Blood. .

Abstract

The prognosis of multiple myeloma is mainly dependent upon chromosomal changes. The 2 major abnormalities driving poor outcome are del(17p) and t(4;14). However, the outcome of these high-risk patients is not absolutely uniform, with some patients presenting long survival. We hypothesized that these better outcomes might be related to concomitant "good-risk" chromosomal changes exploring hyperdiploidy. We analyzed a large series of 965 myeloma patients, including 168 patients with t(4;14) and 126 patients with del(17p), using high-throughput single-nucleotide polymorphism arrays after plasma cell sorting. As expected, trisomic chromosomes were highly associated. Using the LASSO model, we found that only chromosome 3, when trisomic, was associated with a longer progression-free survival and that 3 trisomies modulated overall survival (OS) in myeloma patients: trisomies 3 and 5 significantly improved OS, whereas trisomy 21 worsened OS. In patients with t(4;14), trisomies 3 and/or 5 seemed to overcome the poor prognosis. For the first time, using a specific modeling approach, we show that not all trisomies display the same prognostic impact. This finding could be important for routine assessment of prognosis in myeloma, and some high-risk patients with a traditional evaluation could in fact be standard-risk patients.

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Figures

Figure 1
Figure 1
Graphical representation of the association between trisomies. P values were derived from a χ2 test. Tri, trisomy.
Figure 2
Figure 2
Trisomy 3 improves the PFS of high-risk patients. Kaplan-Meier estimates of TTP according to (A) t(4;14) and trisomy 3 and (B) del(17p) and trisomy 3.
Figure 3
Figure 3
Trisomies 3 and 5 improve the OS of high-risk patients. Kaplan-Meier estimates of OS according to (A) t(4;14) and trisomy 3, (B) t(4;14) and trisomy 5, (C) del(17p) and trisomy 3, and (D) del(17p) and trisomy 5.
Figure 4
Figure 4
Trisomy 21 worsens the OS of high-risk patients. Kaplan-Meier estimates of OS according to (A) t(4;14) and trisomy 21 and (B) del(17p) and trisomy 21. The curves were adjusted on trisomies 3 and 5.
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References

    1. Gertz MA, Lacy MQ, Dispenzieri A, et al. Clinical implications of t(11;14)(q13;q32), t(4;14)(p16.3;q32), and -17p13 in myeloma patients treated with high-dose therapy. Blood. 2005;106(8):2837–2840. - PMC - PubMed
    1. Fonseca R, Blood E, Rue M, et al. Clinical and biologic implications of recurrent genomic aberrations in myeloma. Blood. 2003;101(11):4569–4575. - PubMed
    1. Avet-Loiseau H, Attal M, Moreau P, et al. Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myélome. Blood. 2007;109(8):3489–3495. - PubMed
    1. Hanamura I, Stewart JP, Huang Y, et al. Frequent gain of chromosome band 1q21 in plasma-cell dyscrasias detected by fluorescence in situ hybridization: incidence increases from MGUS to relapsed myeloma and is related to prognosis and disease progression following tandem stem-cell transplantation. Blood. 2006;108(5):1724–1732. - PMC - PubMed
    1. Avet-Loiseau H, Attal M, Campion L, et al. Long-term analysis of the IFM 99 trials for myeloma: cytogenetic abnormalities [t(4;14), del(17p), 1q gains] play a major role in defining long-term survival. J Clin Oncol. 2012;30(16):1949–1952. - PubMed

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