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@ARTICLE{Merz:141402,
author = {M. Merz and A. Jauch and T. Hielscher$^*$ and T. Bochtler
and S. O. Schönland and A. Seckinger and D. Hose and U.
Bertsch and K. Neben and M. S. Raab$^*$ and J. Hillengass
and H. Salwender and I. W. Blau and H.-W. Lindemann and I.
G. H. Schmidt-Wolf and C. Scheid and M. Haenel and K. C.
Weisel and H. Goldschmidt},
title = {{P}rognostic significance of cytogenetic heterogeneity in
patients with newly diagnosed multiple myeloma.},
journal = {Blood advances},
volume = {2},
number = {1},
issn = {2473-9537},
address = {Washington, DC},
publisher = {American Society of Hematology},
reportid = {DKFZ-2018-01908},
pages = {1 - 9},
year = {2018},
abstract = {We investigated subclonal cytogenetic aberrations (CA)
detected by interphase fluorescence in situ hybridization
(iFISH) in patients with newly diagnosed multiple myeloma
(MM) enrolled in the Haemato Oncology Foundation for Adults
in the Netherlands (HOVON)-65/German-Speaking MM Group
(GMMG)-HD4 phase 3 trial. Patients were either treated with
3 cycles of vincristine, Adriamycin, and dexamethasone or
bortezomib, Adriamycin, and dexamethasone and then
thalidomide or bortezomib maintenance after tandem
autologous transplantation. Subclones were defined either by
presence of different copy numbers of the same chromosome
loci and/or CA present in at least $30\%$ less and maximally
2/3 of cells compared with the main clone CA. Patients with
subclones harbored more frequently high risk $(31.0\%)$ or
hyperdiploid main clone aberrations $(24.8\%)$ than patients
with t(11;14) in the main clone $(10.1\%).$ Gains and
deletions of c-MYC were the only CA that occurred more
frequently as subclone $(8.1\%/20.5\%)$ than main clone
$(6.2\%/3.9\%,$ respectively). Treatment with bortezomib
completely overcame the negative prognosis of high-risk CA
in patients without subclones, but not in patients with
additional subclonal CA. High-risk patients treated without
bortezomib showed dismal outcome whether subclones were
present or not. Cytogenetic heterogeneity defined by
subclonal CA is of major prognostic significance in newly
diagnosed MM patients treated with bortezomib within the
HOVON-65/GMMG-HD4 trial.},
cin = {C060 / G170},
ddc = {610},
cid = {I:(DE-He78)C060-20160331 / I:(DE-He78)G170-20160331},
pnm = {313 - Cancer risk factors and prevention (POF3-313)},
pid = {G:(DE-HGF)POF3-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:29344579},
pmc = {pmc:PMC5761630},
doi = {10.1182/bloodadvances.2017013334},
url = {https://inrepo02.dkfz.de/record/141402},
}