Universität zu Köln

Merz, Maximilian, Jauch, Anna, Hielscher, Thomas, Bochtler, Tilmann, Schoenland, Stefan Olaf, Seckinger, Anja, Hose, Dirk, Bertsch, Uta, Neben, Kai, Raab, Marc Steffen, Hillengass, Jens, Salwender, Hans, Blau, Igor Wolfgang, Lindemann, Hans-Walter, Schmidt-Wolf, Ingo G. H., Scheid, Christof, Haenel, Mathias, Weisel, Katja C. and Goldschmidt, Hartmut (2018). Prognostic significance of cytogenetic heterogeneity in patients with newly diagnosed multiple myeloma. Blood Adv., 2 (1). S. 1 - 10. WASHINGTON: AMER SOC HEMATOLOGY. ISSN 2473-9537

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Abstract

We investigated subclonal cytogenetic aberrations (CA) detected by interphase fluorescence in situ hybridization (iFISH) in patients with newly diagnosed multiple myeloma (MM) enrolled in the Haemato Oncology Foundation for Adults in the Netherlands (HOVON)-65/German-Speaking MM Group (GMMG)-HD4 phase 3 trial. Patients were either treated with 3 cycles of vincristine, Adriamycin, and dexamethasone or bortezomib, Adriamycin, and dexamethasone and then thalidomide or bortezomib maintenance after tandem autologous transplantation. Subclones were defined either by presence of different copy numbers of the same chromosome loci and/or CA present in at least 30% less and maximally 2/3 of cells compared with the main clone CA. Patients with subclones harbored more frequently high risk (31.0%) or hyperdiploid main clone aberrations (24.8%) than patients with t(11; 14) in the main clone (10.1%). Gains and deletions of c-MYC were the only CA that occurred more frequently as subclone (8.1%/20.5%) than main clone (6.2%/3.9%, respectively). Treatment with bortezomib completely overcame the negative prognosis of high-risk CA in patients without subclones, but not in patients with additional subclonal CA. High-risk patients treated without bortezomib showed dismal outcome whether subclones were present or not. Cytogenetic heterogeneity defined by subclonal CA is ofmajor prognostic significance in newly diagnosed MM patients treated with bortezomib within the HOVON-65/GMMG-HD4 trial.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Merz, Maximilian UNSPECIFIED UNSPECIFIED UNSPECIFIED Jauch, Anna UNSPECIFIED UNSPECIFIED UNSPECIFIED Hielscher, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Bochtler, Tilmann UNSPECIFIED UNSPECIFIED UNSPECIFIED Schoenland, Stefan Olaf UNSPECIFIED UNSPECIFIED UNSPECIFIED Seckinger, Anja UNSPECIFIED UNSPECIFIED UNSPECIFIED Hose, Dirk UNSPECIFIED UNSPECIFIED UNSPECIFIED Bertsch, Uta UNSPECIFIED UNSPECIFIED UNSPECIFIED Neben, Kai UNSPECIFIED UNSPECIFIED UNSPECIFIED Raab, Marc Steffen UNSPECIFIED UNSPECIFIED UNSPECIFIED Hillengass, Jens UNSPECIFIED UNSPECIFIED UNSPECIFIED Salwender, Hans UNSPECIFIED UNSPECIFIED UNSPECIFIED Blau, Igor Wolfgang UNSPECIFIED UNSPECIFIED UNSPECIFIED Lindemann, Hans-Walter UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmidt-Wolf, Ingo G. H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Scheid, Christof UNSPECIFIED UNSPECIFIED UNSPECIFIED Haenel, Mathias UNSPECIFIED UNSPECIFIED UNSPECIFIED Weisel, Katja C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Goldschmidt, Hartmut UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-199024
DOI:	10.1182/bloodadvances.2017013334
Journal or Publication Title:	Blood Adv.
Volume:	2
Number:	1
Page Range:	S. 1 - 10
Date:	2018
Publisher:	AMER SOC HEMATOLOGY
Place of Publication:	WASHINGTON
ISSN:	2473-9537
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language IN-SITU HYBRIDIZATION; HIGH-RISK PATIENTS; DELETION 17P; HOVON-65/GMMG-HD4 TRIAL; TRANSPLANTATION; BORTEZOMIB; EVOLUTION; DEXAMETHASONE; TRISOMIES; SUBGROUP Multiple languages Hematology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/19902