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@ARTICLE{Bochtler:126161,
author = {T. Bochtler$^*$ and U. Hegenbart and C. Kunz$^*$ and M.
Granzow and A. Benner$^*$ and A. Seckinger and C. Kimmich
and H. Goldschmidt and A. D. Ho and D. Hose and A. Jauch and
S. O. Schönland},
title = {{T}ranslocation t(11;14) is associated with adverse outcome
in patients with newly diagnosed {AL} amyloidosis when
treated with bortezomib-based regimens.},
journal = {Journal of clinical oncology},
volume = {33},
number = {12},
issn = {1527-7755},
address = {Alexandria, Va.},
publisher = {American Society of Clinical Oncology},
reportid = {DKFZ-2017-02276},
pages = {1371 - 1378},
year = {2015},
abstract = {Bortezomib has become a cornerstone in the treatment of AL
amyloidosis. In this study, we addressed the prognostic
impact of cytogenetic aberrations for bortezomib-treated
patients.We analyzed a consecutive series of 101 patients
with AL amyloidosis treated with bortezomib-dexamethasone as
first-line treatment by interphase fluorescence in situ
hybridization (iFISH). Patients were ineligible for
high-dose chemotherapy, which would put them at risk for
cardiac or renal failure, and thus represented a poor-risk
group.Presence of t(11;14), versus its absence, was
associated with inferior hematologic event-free survival
(median, 3.4 v 8.8 months, respectively; P = .002), overall
survival (median, 8.7 v 40.7 months, respectively; P = .05),
and remission rate (≥ very good partial remission; $23\%$
v $47\%,$ respectively; P = .02). In multivariable Cox
regression models incorporating established hematologic and
clinical risk factors, t(11;14) was an independent adverse
prognostic marker for hematologic event-free survival
(hazard ratio, 2.94; $95\%$ CI, 1.37 to 6.25; P = .006) and
overall survival (hazard ratio, 3.13; $95\%$ CI, 1.16 to
8.33; P = .03), but not for remission (≥ very good partial
remission). Markedly, the multiple myeloma high-risk iFISH
aberrations t(4;14), t(14;16), del(17p), and gain of 1q21
conferred no adverse prognosis in this
bortezomib-dexamethasone-treated group. After backward
variable selection, the final multivariable model was
validated in a consecutive series of 32 patients treated
with bortezomib, dexamethasone, and cyclophosphamide.iFISH
results are important independent prognostic factors in AL
amyloidosis. In contrast to our recently published results
with melphalan and dexamethasone standard therapy,
bortezomib is less beneficial to patients harboring
t(11;14), whereas it effectively alleviates the poor
prognosis inherent to high-risk aberrations. Given the
discrepant response to different treatment modalities, iFISH
may help to guide therapeutic choices in these poor-risk
patients requiring rapid hematologic response.},
keywords = {Boronic Acids (NLM Chemicals) / Immunoglobulin Light Chains
(NLM Chemicals) / Pyrazines (NLM Chemicals) / Bortezomib
(NLM Chemicals) / Dexamethasone (NLM Chemicals) /
Cyclophosphamide (NLM Chemicals)},
cin = {G330 / C060},
ddc = {050},
cid = {I:(DE-He78)G330-20160331 / I:(DE-He78)C060-20160331},
pnm = {317 - Translational cancer research (POF3-317)},
pid = {G:(DE-HGF)POF3-317},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:25779559},
doi = {10.1200/JCO.2014.57.4947},
url = {https://inrepo02.dkfz.de/record/126161},
}