TY  - JOUR
A1  - Bachmann, Friederike
A1  - Schreder, Martin
A1  - Engelhardt, Monika
A1  - Langer, Christian
A1  - Wolleschak, Denise
A1  - Mügge, Lars Olof
A1  - Dürk, Heinz
A1  - Schäfer-Eckart, Kerstin
A1  - Blau, Igor Wolfgang
A1  - Gramatzki, Martin
A1  - Liebisch, Peter
A1  - Grube, Matthias
A1  - Metzler, Ivana v.
A1  - Bassermann, Florian
A1  - Metzner, Bernd
A1  - Röllig, Christoph
A1  - Hertenstein, Bernd
A1  - Khandanpour, Cyrus
A1  - Dechow, Tobias
A1  - Hebart, Holger
A1  - Jung, Wolfram
A1  - Theurich, Sebastian
A1  - Maschmeyer, Georg
A1  - Salwender, Hans
A1  - Hess, Georg
A1  - Bittrich, Max
A1  - Rasche, Leo
A1  - Brioli, Annamaria
A1  - Eckardt, Kai-Uwe
A1  - Straka, Christian
A1  - Held, Swantje
A1  - Einsele, Hermann
A1  - Knop, Stefan
T1  - Kinetics of renal function during induction in newly diagnosed multiple myeloma: results of two prospective studies by the German Myeloma Study Group DSMM
JF  - Cancers
N2  - Background: Preservation of kidney function in newly diagnosed (ND) multiple myeloma (MM) helps to prevent excess toxicity. Patients (pts) from two prospective trials were analyzed, provided postinduction (PInd) restaging was performed. Pts received three cycles with bortezomib (btz), cyclophosphamide, and dexamethasone (dex; VCD) or btz, lenalidomide (len), and dex (VRd) or len, adriamycin, and dex (RAD). The minimum required estimated glomerular filtration rate (eGFR) was >30 mL/min. We analyzed the percent change of the renal function using the International Myeloma Working Group (IMWG) criteria and Kidney Disease: Improving Global Outcomes (KDIGO)-defined categories. Results: Seven hundred and seventy-two patients were eligible. Three hundred and fifty-six received VCD, 214 VRd, and 202 RAD. VCD patients had the best baseline eGFR. The proportion of pts with eGFR <45 mL/min decreased from 7.3% at baseline to 1.9% PInd (p < 0.0001). Thirty-seven point one percent of VCD versus 49% of VRd patients had a decrease of GFR (p = 0.0872). IMWG-defined “renal complete response (CRrenal)” was achieved in 17/25 (68%) pts after VCD, 12/19 (63%) after RAD, and 14/27 (52%) after VRd (p = 0.4747). Conclusions: Analyzing a large and representative newly diagnosed myeloma (NDMM) group, we found no difference in CRrenal that occurred independently from the myeloma response across the three regimens. A trend towards deterioration of the renal function with VRd versus VCD may be explained by a better pretreatment “renal fitness” in the latter group.
KW  - multiple myeloma
KW  - renal failure
KW  - kidney
KW  - bortezomib
KW  - lenalidomide
KW  - induction regimen
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-234139
SN  - 2072-6694
VL  - 13
IS  - 6
ER  - 
TY  - JOUR
A1  - Eckardt, Jan-Niklas
A1  - Stasik, Sebastian
A1  - Kramer, Michael
A1  - Röllig, Christoph
A1  - Krämer, Alwin
A1  - Scholl, Sebastian
A1  - Hochhaus, Andreas
A1  - Crysandt, Martina
A1  - Brümmendorf, Tim H.
A1  - Naumann, Ralph
A1  - Steffen, Björn
A1  - Kunzmann, Volker
A1  - Einsele, Hermann
A1  - Schaich, Markus
A1  - Burchert, Andreas
A1  - Neubauer, Andreas
A1  - Schäfer-Eckart, Kerstin
A1  - Schliemann, Christoph
A1  - Krause, Stefan W.
A1  - Herbst, Regina
A1  - Hänel, Mathias
A1  - Frickhofen, Norbert
A1  - Noppeney, Richard
A1  - Kaiser, Ulrich
A1  - Baldus, Claudia D.
A1  - Kaufmann, Martin
A1  - Rácil, Zdenek
A1  - Platzbecker, Uwe
A1  - Berdel, Wolfgang E.
A1  - Mayer, Jiří
A1  - Serve, Hubert
A1  - Müller-Tidow, Carsten
A1  - Ehninger, Gerhard
A1  - Stölzel, Friedrich
A1  - Kroschinsky, Frank
A1  - Schetelig, Johannes
A1  - Bornhäuser, Martin
A1  - Thiede, Christian
A1  - Middeke, Jan Moritz
T1  - Loss-of-function mutations of BCOR are an independent marker of adverse outcomes in intensively treated patients with acute myeloid leukemia
JF  - Cancers
N2  - Acute myeloid leukemia (AML) is characterized by recurrent genetic events. The BCL6 corepressor (BCOR) and its homolog, the BCL6 corepressor-like 1 (BCORL1), have been reported to be rare but recurrent mutations in AML. Previously, smaller studies have reported conflicting results regarding impacts on outcomes. Here, we retrospectively analyzed a large cohort of 1529 patients with newly diagnosed and intensively treated AML. BCOR and BCORL1 mutations were found in 71 (4.6%) and 53 patients (3.5%), respectively. Frequently co-mutated genes were DNTM3A, TET2 and RUNX1. Mutated BCORL1 and loss-of-function mutations of BCOR were significantly more common in the ELN2017 intermediate-risk group. Patients harboring loss-of-function mutations of BCOR had a significantly reduced median event-free survival (HR = 1.464 (95%-Confidence Interval (CI): 1.005–2.134), p = 0.047), relapse-free survival (HR = 1.904 (95%-CI: 1.163–3.117), p = 0.01), and trend for reduced overall survival (HR = 1.495 (95%-CI: 0.990–2.258), p = 0.056) in multivariable analysis. Our study establishes a novel role for loss-of-function mutations of BCOR regarding risk stratification in AML, which may influence treatment allocation.
KW  - acute myeloid leukemia
KW  - BCOR
KW  - BCORL1
KW  - loss-of-function
KW  - risk stratification
KW  - survival
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236735
SN  - 2072-6694
VL  - 13
IS  - 9
ER  - 
TY  - JOUR
A1  - Wagner-Drouet, Eva
A1  - Teschner, Daniel
A1  - Wolschke, Christine
A1  - Schäfer-Eckart, Kerstin
A1  - Gärtner, Johannes
A1  - Mielke, Stephan
A1  - Schreder, Martin
A1  - Kobbe, Guido
A1  - Hilgendorf, Inken
A1  - Klein, Stefan
A1  - Verbeek, Mareike
A1  - Ditschkowski, Markus
A1  - Koch, Martina
A1  - Lindemann, Monika
A1  - Schmidt, Traudel
A1  - Rascle, Anne
A1  - Barabas, Sascha
A1  - Deml, Ludwig
A1  - Wagner, Ralf
A1  - Wolff, Daniel
T1  - Comparison of cytomegalovirus-specific immune cell response to proteins versus peptides using an IFN-γ ELISpot assay after hematopoietic stem cell transplantation
JF  - Diagnostics
N2  - Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality following hematopoietic stem cell transplantation (HSCT). Measuring CMV-specific cellular immunity may improve the risk stratification and management of patients. IFN-γ ELISpot assays, based on the stimulation of peripheral blood mononuclear cells with CMV pp65 and IE-1 proteins or peptides, have been validated in clinical settings. However, it remains unclear to which extend the T-cell response to synthetic peptides reflect that mediated by full-length proteins processed by antigen-presenting cells. We compared the stimulating ability of pp65 and IE-1 proteins and corresponding overlapping peptides in 16 HSCT recipients using a standardized IFN-γ ELISpot assay. Paired qualitative test results showed an overall 74.4% concordance. Discordant results were mainly due to low-response tests, with one exception. One patient with early CMV reactivation and graft-versus-host disease, sustained CMV DNAemia and high CD8\(^+\) counts showed successive negative protein-based ELISpot results but a high and sustained response to IE-1 peptides. Our results suggest that the response to exogenous proteins, which involves their uptake and processing by antigen-presenting cells, more closely reflects the physiological response to CMV infection, while the response to exogenous peptides may lead to artificial in vitro T-cell responses, especially in strongly immunosuppressed patients.
KW  - CMV
KW  - CMV-specific cellular immunity
KW  - hematopoietic stem cell transplantation
KW  - recall antigen
KW  - peptide
KW  - immune monitoring
KW  - IFN-γ ELISpot
KW  - T cells
KW  - antigen processing and presentation
KW  - immunosuppression
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-228843
SN  - 2075-4418
VL  - 11
IS  - 2
ER  -