Longitudinal fluorescence in situ hybridization reveals cytogenetic evolution in myeloma relapsing after autologous transplantation
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 cyto...
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| Main Authors: | , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
May 11, 2017
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| In: |
Haematologica
Year: 2017, Volume: 102, Issue: 8, Pages: 1432-1438 |
| ISSN: | 1592-8721 |
| DOI: | 10.3324/haematol.2017.168005 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.3324/haematol.2017.168005 Verlag, Volltext: http://www.haematologica.org/content/102/8/1432 
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| Author Notes: | Maximilian Merz, Anna Jauch, Thomas Hielscher, Elias K. Mai, Anja Seckinger, Dirk Hose, Uta Bertsch, Kai Neben, Marc S. Raab, Hans Salwender, Igor W. Blau, Hans-Walter Lindemann, Ingo Schmidt-Wolf, Christof Scheid, Mathias Haenel, Katja Weisel, Hartmut Goldschmidt, and Jens Hillengass |
| Summary: | 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). |
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| Item Description: | Pre-published: May 11, 2017 Gesehen am 27.09.2018 |
| Physical Description: | Online Resource |
| ISSN: | 1592-8721 |
| DOI: | 10.3324/haematol.2017.168005 |