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Haematologica. 2017 Aug;102(8):1432-1438. doi: 10.3324/haematol.2017.168005. Epub 2017 May 11.

Longitudinal fluorescence in situ hybridization reveals cytogenetic evolution in myeloma relapsing after autologous transplantation.

Author information

1
Medizinische Klinik V, University Hospital Heidelberg, Heidelberg, Germany maximilian.merz@med.uni-heidelberg.de.
2
Institute of Human Genetics, University Heidelberg, Heidelberg, Germany.
3
Division of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
4
Medizinische Klinik V, University Hospital Heidelberg, Heidelberg, Germany.
5
Max-Eder Research Group Experimental Therapies for Hematologic Malignancies, DKFZ, Heidelberg, Germany.
6
Asklepios Klinik Altona, Hamburg, Germany.
7
Department of Internal Medicine III, Charité Campus Benjamin Franklin, Berlin, Germany.
8
Hämatologie/Onkologie, Kath. Krankenhaus Hagen gem. GmbH - St.-Marien-Hospital, Hagen, Germany.
9
Center for Integrated Oncology, Med. Klinik und Poliklinik III, University of Bonn, Heidelberg, Germany.
10
Department of Internal Medicine I, University of Cologne, Heidelberg, Germany.
11
Klinikum Chemnitz gGmbH, Heidelberg, Germany.
12
University Hospital of Tübingen, Heidelberg, Germany.
13
National Center for Tumor Diseases (NCT), Heidelberg, Germany.
14
Department of Radiology, German Cancer Research Center DKFZ, Heidelberg, Germany.

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).

PMID:
28495913
PMCID:
PMC5541876
DOI:
10.3324/haematol.2017.168005
[Indexed for MEDLINE]
Free PMC Article

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