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@ARTICLE{Merz:128100,
      author       = {M. Merz and A. Jauch and T. Hielscher$^*$ and E. K. Mai and
                      A. Seckinger and D. Hose and U. Bertsch and K. Neben and
                      M.-S. Raab$^*$ and H. Salwender and I. W. Blau and H.-W.
                      Lindemann and I. Schmidt-Wolf and C. Scheid and M. Haenel
                      and K. Weisel and H. Goldschmidt and J. Hillengass$^*$},
      title        = {{L}ongitudinal fluorescence in situ hybridization reveals
                      cytogenetic evolution in myeloma relapsing after autologous
                      transplantation.},
      journal      = {Haematologica},
      volume       = {102},
      number       = {8},
      issn         = {1592-8721},
      address      = {Pavia},
      publisher    = {Ferrata Storti Foundation},
      reportid     = {DKFZ-2017-04122},
      pages        = {1432 - 1438},
      year         = {2017},
      abstract     = {To investigate cytogenetic evolution after upfront
                      autologous stem cell transplantation for newly diagnosed
                      myeloma we retrospectively analyzed fluorescence in situ
                      hybridization results of 128 patients with paired bone
                      marrow samples from the time of primary diagnosis and at
                      relapse. High-risk cytogenetic abnormalities (deletion 17p
                      and/or gain 1q21) occurred more frequently after relapse
                      (odds ratio: 6.33; $95\%$ confidence interval: 1.86-33.42;
                      P<0.001). No significant changes were observed for defined
                      IGH translocations [t(4;14); t(11;14); t(14;16)] or
                      hyperdiploid karyotypes between primary diagnosis and
                      relapse. IGH translocations with unknown partners occurred
                      more frequently at relapse. New deletion 17p and/or gain
                      1q21 were associated with cytogenetic heterogeneity, since
                      some de novo lesions with different copy numbers were
                      present only in subclones. No distinct baseline
                      characteristics were associated with the occurrence of new
                      high-risk cytogenetic abnormalities after progression.
                      Patients who relapsed after novel agent-based induction
                      therapy had an increased risk of developing high-risk
                      aberrations (odds ratio 10.82; $95\%$ confidence interval:
                      1.65-127.66; P=0.03) compared to those who were treated with
                      conventional chemotherapy. Survival analysis revealed dismal
                      outcomes regardless of whether high-risk aberrations were
                      present at baseline (hazard ratio, 3.53; $95\%$ confidence
                      interval: 1.53-8.14; P=0.003) or developed at relapse only
                      (hazard ratio, 3.06; $95\%$ confidence interval: 1.09-8.59;
                      P=0.03). Our results demonstrate cytogenetic evolution
                      towards high-risk disease after autologous transplantation
                      and underline the importance of repeated genetic testing in
                      relapsed myeloma (EudraCT number of the HD4 trial:
                      2004-000944-26).},
      cin          = {C060 / G170 / E010},
      ddc          = {610},
      cid          = {I:(DE-He78)C060-20160331 / I:(DE-He78)G170-20160331 /
                      I:(DE-He78)E010-20160331},
      pnm          = {315 - Imaging and radiooncology (POF3-315)},
      pid          = {G:(DE-HGF)POF3-315},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:28495913},
      pmc          = {pmc:PMC5541876},
      doi          = {10.3324/haematol.2017.168005},
      url          = {https://inrepo02.dkfz.de/record/128100},
}