Merz, Maximilian, Jauch, Anna, Hielscher, Thomas, Mai, Elias K., Seckinger, Anja, Hose, Dirk, Bertsch, Uta, Neben, Kai, Raab, Marc S., Salwender, Hans ORCID: 0000-0001-7803-0814, Blau, Igor W., Lindemann, Hans-Walter, Schmidt-Wolf, Ingo, Scheid, Christof, Haenel, Mathias, Weisel, Katja, Goldschmidt, Hartmut and Hillengass, Jens (2017). Longitudinal fluorescence in situ hybridization reveals cytogenetic evolution in myeloma relapsing after autologous transplantation. Haematologica, 102 (8). S. 1432 - 1439. PAVIA: FERRATA STORTI FOUNDATION. ISSN 0390-6078

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Merz, MaximilianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jauch, AnnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hielscher, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mai, Elias K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Seckinger, AnjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hose, DirkUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bertsch, UtaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Neben, KaiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Raab, Marc S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Salwender, HansUNSPECIFIEDorcid.org/0000-0001-7803-0814UNSPECIFIED
Blau, Igor W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lindemann, Hans-WalterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmidt-Wolf, IngoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Scheid, ChristofUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haenel, MathiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weisel, KatjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Goldschmidt, HartmutUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hillengass, JensUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-223301
DOI: 10.3324/haematol.2017.168005
Journal or Publication Title: Haematologica
Volume: 102
Number: 8
Page Range: S. 1432 - 1439
Date: 2017
Publisher: FERRATA STORTI FOUNDATION
Place of Publication: PAVIA
ISSN: 0390-6078
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
STEM-CELL TRANSPLANTATION; MULTIPLE-MYELOMA; THERAPY; PROGRESSION; RISK; ABNORMALITIES; HYPERDIPLOIDY; BORTEZOMIB; PROGNOSIS; DEL(17P)Multiple languages
HematologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/22330

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