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@ARTICLE{Oubari:300104,
author = {S. Oubari and M. Papathanasiou and L. Michel and T. Rassaf
and A. Thimm and T. Hagenacker and D. Ehling and S.
Wieczorek and E. Naser and U. Hegenbart and S. Schönland
and U. Dührsen and H. C. Reinhardt$^*$ and A. Carpinteiro},
title = {{G}ain or amplification of 1q21 in systemic light chain
amyloidosis is associated with advanced {M}ayo stage, plasma
cell disease and worse overall survival.},
journal = {Annals of hematology},
volume = {104},
number = {3},
issn = {0939-5555},
address = {New York},
publisher = {Springer},
reportid = {DKFZ-2025-00604},
pages = {1777-1788},
year = {2025},
note = {2025 Mar;104(3):1777-1788},
abstract = {Systemic light-chain amyloidosis (AL) is an acquired
protein misfolding disease characterized by deposition of
immunoglobulin light-chain fibrils most often secreted from
clonal plasma cells. In this retrospective study we analyzed
the impact of iFISH aberrations on clinical characteristics
and outcomes in 175 AL patients presented between 2015 and
2024. The most common aberrations were t(11;14) $(57\%),$
deletion 13q14 $(33\%),$ +1q21 $(21\%),$ hyperdiploidy
$(21\%)$ and deletion 16q23 $(17\%).$ Significant elevations
in dFLC levels were observed in patients with + 1q21 (median
407 vs. 213 mg/l, p = 0.04) and deletion 16q23 (median 476
vs. 204, p = 0.006). Only + 1q21 was associated with
increased levels of cardiac biomarkers NTproBNP (median 9945
vs. 3538 pg/ml, p = 0.002) and hsTnT (median 110 vs. 53
ng/l, p = 0.002). This resulted in an increased proportion
of patients with Mayo stage IIIb $(53\%$ vs. $26\%,$ p =
0.01). Patients with + 1q21 had more advanced plasma cell
disease (p = 0.0004). Our study highlights for the first
time + 1q21 as the key aberration associated with advanced
cardiac and plasma cell disease. After 17 months of
follow-up, overall survival was significantly worse in
patients with + 1q21 treated with daratumumab (7.2 months
vs. not reached, p = 0.006). Alternative therapeutic
approaches such as CAR-T therapies or bispecific antibodies
should be further investigated.},
keywords = {+1q21 (Other) / AL amyloidosis (Other) / IFISH (Other) /
Mayo stage (Other)},
cin = {ED01},
ddc = {610},
cid = {I:(DE-He78)ED01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40119178},
doi = {10.1007/s00277-025-06256-7},
url = {https://inrepo02.dkfz.de/record/300104},
}