@article{SteinhardtKrummenastRosenwaldetal.2022, author = {Steinhardt, Maximilian J. and Krummenast, Franziska C. and Rosenwald, Andreas and Gerhard-Hartmann, Elena and Heidemeier, Anke and Einsele, Hermann and Topp, Max S. and Duell, Johannes}, title = {R-CHOP intensification with mid-cycle methotrexate and consolidating AraC/TT with BCNU/aHSCT in primary aggressive lymphoma with CNS involvement}, series = {Journal of Cancer Research and Clinical Oncology}, volume = {148}, journal = {Journal of Cancer Research and Clinical Oncology}, number = {1}, issn = {1432-1335}, doi = {10.1007/s00432-021-03663-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-267731}, pages = {205-214}, year = {2022}, abstract = {Purpose Patients suffering from aggressive systemic peripheral lymphoma with primary central nervous system involvement (PCL) are a rare and sparsely investigated population. Recommended treatment regimens include a combination of intrathecal and systemic chemotherapy as well as whole brain radiotherapy while offering relatively poor survival. Methods We conducted a single-center retrospective study that analyzed safety and outcome of 4 + 4 cycles Rituximab (R)-CHOP and R-high-dose Methotrexate (HD-MTX) for newly diagnosed, transplant-eligible patients ("Ping-Pong"), followed by Cytarabine (AraC)/Thiotepa (TT), BCNU/TT, and autologous hematologic stem cell transplantation (aHSCT). We retrospectively analyzed a set of 16 patients with high-intermediate or high-risk IPI status. Results Overall response rate to Ping-Pong was 100\% measured by CT/MRI, including 93.75\% complete remissions after BCNU/TT followed by PBSCT. One patient failed to qualify for high-dose chemotherapy due to progression when receiving Cytarabine/TT. All patients experienced grade III adverse events, 3 of them a grade IV adverse event. Estimated progression-free survival is 93.75\% after a 4.8-year follow-up currently. Conclusion Our study suggests high effectivity of R-CHOP with mid-cycle MTX with aHSCT consolidation towards acceptable OS results in this challenging patient population.}, language = {en} } @article{PorubskyPopovicBadveetal.2021, author = {Porubsky, Stefan and Popovic, Zoran V. and Badve, Sunil and Banz, Yara and Berezowska, Sabina and Borchert, Dietmar and Br{\"u}ggemann, Monika and Gaiser, Timo and Graeter, Thomas and Hollaus, Peter and Huettl, Katrin S. and Kotrova, Michaela and Kreft, Andreas and Kugler, Christian and L{\"o}tscher, Fabian and M{\"o}ller, Burkhard and Ott, German and Preissler, Gerhard and Roessner, Eric and Rosenwald, Andreas and Str{\"o}bel, Philipp and Marx, Alexander}, title = {Thymic hyperplasia with lymphoepithelial sialadenitis (LESA)-like features: strong association with lymphomas and non-myasthenic autoimmune diseases}, series = {Cancers}, volume = {13}, journal = {Cancers}, number = {2}, issn = {2072-6694}, doi = {10.3390/cancers13020315}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-223049}, year = {2021}, abstract = {Thymic hyperplasia (TH) with lymphoepithelial sialadenitis (LESA)-like features (LESA-like TH) has been described as a tumor-like, benign proliferation of thymic epithelial cells and lymphoid follicles. We aimed to determine the frequency of lymphoma and autoimmunity in LESA-like TH and performed retrospective analysis of cases with LESA-like TH and/or thymic MALT-lymphoma. Among 36 patients (21 males) with LESA-like TH (age 52 years, 32-80; lesion diameter 7.0 cm, 1-14.5; median, range), five (14\%) showed associated lymphomas, including four (11\%) thymic MALT lymphomas and one (3\%) diffuse large B-cell lymphoma. One additional case showed a clonal B-cell-receptor rearrangement without evidence of lymphoma. Twelve (33\%) patients (7 women) suffered from partially overlapping autoimmune diseases: systemic lupus erythematosus (n = 4, 11\%), rheumatoid arthritis (n = 3, 8\%), myasthenia gravis (n = 2, 6\%), asthma (n = 2, 6\%), scleroderma, Sj{\"o}gren syndrome, pure red cell aplasia, Grave's disease and anti-IgLON5 syndrome (each n = 1, 3\%). Among 11 primary thymic MALT lymphomas, remnants of LESA-like TH were found in two cases (18\%). In summary, LESA-like TH shows a striking association with autoimmunity and predisposes to lymphomas. Thus, a hematologic and rheumatologic workup should become standard in patients diagnosed with LESA-like TH. Radiologists and clinicians should be aware of LESA-like TH as a differential diagnosis for mediastinal mass lesions in patients with autoimmune diseases.}, language = {en} } @article{ShiKuaiLeietal.2016, author = {Shi, Yaoyao and Kuai, Yue and Lei, Lizhen and Weng, Yuanyuan and Berberich-Siebelt, Friederike and Zhang, Xinxia and Wang, Jinjie and Zhou, Yuan and Jiang, Xin and Ren, Guoping and Pan, Hongyang and Mao, Zhengrong and Zhou, Ren}, title = {The feedback loop of LITAF and BCL6 is involved in regulating apoptosis in B cell non-Hodgkin's-lymphoma}, series = {Oncotarget}, volume = {7}, journal = {Oncotarget}, number = {47}, doi = {10.18632/oncotarget.12680}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166500}, pages = {77444-77456}, year = {2016}, abstract = {Dysregulation of the apoptotic pathway is widely recognized as a key step in lymphomagenesis. Notably, LITAF was initially identified as a p53-inducible gene, subsequently implicated as a tumor suppressor. Our previous study also showed LITAF to be methylated in 89.5\% B-NHL samples. Conversely, deregulated expression of BCL6 is a pathogenic event in many lymphomas. Interestingly, our study found an oppositional expression of LITAF and BCL6 in B-NHL. In addition, LITAF was recently identified as a novel target gene of BCL6. Therefore, we sought to explore the feedback loop between LITAF and BCL6 in B-NHL. Here, our data for the first time show that LITAF can repress expression of BCL6 by binding to Region A (-87 to +65) containing a putative LITAF-binding motif (CTCCC) within the BCL6 promoter. Furthermore, the regulation of BCL6 targets (PRDM1 or c-Myc) by LITAF may be associated with B-cell differentiation. Results also demonstrate that ectopic expression of LITAF induces cell apoptosis, activated by releasing cytochrome c, cleaving PARP and caspase 3 in B-NHL cells whereas knockdown of LITAF robustly protected cells from apoptosis. Interestingly, BCL6, in turn, could reverse cell apoptosis mediated by LITAF. Collectively, our findings provide a novel apoptotic regulatory pathway in which LITAF, as a transcription factor, inhibits the expression of BCL6, which leads to activation of the intrinsic mitochondrial pathway and tumor apoptosis. Our study is expected to provide a possible biomarker as well as a target for clinical therapies to promote tumor cell apoptosis.}, language = {en} } @article{HerrmannQueirozHuellneretal.2015, author = {Herrmann, Ken and Queiroz, Marcelo and Huellner, Martin W. and Barbosa, Felipe de Galiza and Buck, Andreas and Schaefer, Niklaus and Stolzman, Paul and Veit-Haibach, Patrick}, title = {Diagnostic performance of FDG-PET/MRI and WB-DW-MRI in the evaluation of lymphoma: a prospective comparison to standard FDG-PET/CT}, series = {BMC Cancer}, volume = {15}, journal = {BMC Cancer}, number = {1002}, doi = {10.1186/s12885-015-2009-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-136039}, year = {2015}, abstract = {Background: Use of FDG-PET/CT for staging and restaging of lymphoma patients is widely incorporated into current practice guidelines. Our aim was to prospectively evaluate the diagnostic performance of FDG-PET/MRI and WB-DW-MRI compared with FDG-FDG-PET/CT using a tri-modality PET/CT-MRI system. Methods: From 04/12 to 01/14, a total of 82 FDG-PET/CT examinations including an additional scientific MRI on a tri-modality setup were performed in 61 patients. FDG-PET/CT, FDG-PET/MRI, and WB-DW-MRI were independently analyzed. A lesion with a mean ADC below a threshold of 1.2 x 10\(^{-3}\) mm\(^2\)/s was defined as positive for restricted diffusion. FDG-PET/CT and FDG-PET/MRI were evaluated for the detection of lesions corresponding to lymphoma manifestations according to the German Hodgkin Study Group. Imaging findings were validated by biopsy (n = 21), by follow-up imaging comprising CT, FDG-PET/CT, and/or FDG-PET/MRI (n = 32), or clinically (n = 25) (mean follow-up: 9.1 months). Results: FDG-PET/MRI and FDG-PET/CT accurately detected 188 lesions in 27 patients. Another 54 examinations in 35 patients were negative. WB-DW-MRI detected 524 lesions, of which 125 (66.5 \% of the aforementioned 188 lesions) were true positive. Among the 188 lesions positive for lymphoma, FDG-PET/MRI detected all 170 instances of nodal disease and also all 18 extranodal lymphoma manifestations; by comparison, WB-DW-MRI characterized 115 (67.6 \%) and 10 (55.6 \%) lesions as positive for nodal and extranodal disease, respectively. FDG-PET/MRI was superior to WB-DW-MRI in detecting lymphoma manifestations in patients included for staging (113 vs. 73), for restaging (75 vs. 52), for evaluation of high-(127 vs. 81) and low-grade lymphomas (61 vs. 46), and for definition of Ann Arbor stage (WB-DW-MRI resulted in upstaging in 60 cases, including 45 patients free of disease, and downstaging in 4). Conclusion: Our results indicate that FDG-PET/CT and FDG-PET/MRI probably have a similar performance in the clinical work-up of lymphomas. The performance of WB-DW-MRI was generally inferior to that of both FDG-PET-based methods but the technique might be used in specific scenarios, e.g., in low-grade lymphomas and during surveillance.}, language = {en} } @article{WesterKellerSchotteliusetal.2015, author = {Wester, Hans J{\"u}rgen and Keller, Ulrich and Schottelius, Margret and Beer, Ambros and Philipp-Abbrederis, Kathrin and Hoffmann, Frauke and Šimeček, Jakub and Gerngross, Carlos and Lassmann, Michael and Herrmann, Ken and Pellegata, Natalia and Rudelius, Martina and Kessler, Horst and Schwaiger, Markus}, title = {Disclosing the CXCR4 expression in lymphoproliferative diseases by targeted molecular imaging}, series = {Theranostics}, volume = {5}, journal = {Theranostics}, number = {6}, doi = {10.7150/thno.11251}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-144537}, pages = {618-630}, year = {2015}, abstract = {Chemokine ligand-receptor interactions play a pivotal role in cell attraction and cellular trafficking, both in normal tissue homeostasis and in disease. In cancer, chemokine receptor-4 (CXCR4) expression is an adverse prognostic factor. Early clinical studies suggest that targeting CXCR4 with suitable high-affinity antagonists might be a novel means for therapy. In addition to the preclinical evaluation of [\(^{68}\)Ga]Pentixafor in mice bearing human lymphoma xenografts as an exemplary CXCR4-expressing tumor entity, we report on the first clinical applications of [\(^{68}\)Ga]Pentixafor-Positron Emission Tomography as a powerful method for CXCR4 imaging in cancer patients. [\(^{68}\)Ga]Pentixafor binds with high affinity and selectivity to human CXCR4 and exhibits a favorable dosimetry. [\(^{68}\)Ga]Pentixafor-PET provides images with excellent specificity and contrast. This non-invasive imaging technology for quantitative assessment of CXCR4 expression allows to further elucidate the role of CXCR4/CXCL12 ligand interaction in the pathogenesis and treatment of cancer, cardiovascular diseases and autoimmune and inflammatory disorders.}, language = {en} } @article{HerrmannBuckSchusteretal.2014, author = {Herrmann, Ken and Buck, Andreas K. and Schuster, Tibor and Abbrederis, Kathrin and Bl{\"u}mel, Christina and Santi, Ivan and Rudelius, Martina and Wester, Hans-J{\"u}rgen and Peschel, Christian and Schwaiger, Markus and Dechow, Tobias and Keller, Ulrich}, title = {Week one FLT-PET response predicts complete remission to R-CHOP and survival in DLBCL}, series = {Oncotarget}, volume = {5}, journal = {Oncotarget}, number = {12}, issn = {1949-2553}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-120659}, pages = {4050-59}, year = {2014}, abstract = {Despite improved survival in the Rituximab (R) era, a considerable number of patients with diffuse large B-cell lymphoma (DLBCL) ultimately die from the disease. Functional imaging using [18F]fluorodeoxyglucose-PET is suggested for assessment of residual viable tumor very early during treatment but is compromised by non-specific tracer retention in inflammatory lesions. The PET tracer [18F]fluorodeoxythymidine (FLT) as surrogate marker of tumor proliferation may overcome this limitation. We present results of a prospective clinical study testing FLT-PET as superior and early predictor of response to chemotherapy and outcome in DLBCL. 54 patients underwent FLT-PET prior to and one week after the start of R-CHOP chemotherapy. Repetitive FLT-PET imaging was readily implemented into the diagnostic work-up. Our data demonstrate that the reduction of FLT standard uptake valuemean (SUVmean) and SUVmax one week after chemotherapy was significantly higher in patients achieving complete response (CR, n=48; non-CR, n=6; p<0.006). Martingale-residual and Cox proportional hazard analyses showed a significant monotonous decrease of mortality risk with increasing change in SUV. Consistent with these results, early FLT-PET response showed relevant discriminative ability in predicting CR. In conclusion, very early FLT-PET in the course of R-CHOP chemotherapy is feasible and enables identification of patients at risk for treatment failure.}, language = {en} } @article{PatelMurphyHaralmbievaetal.2014, author = {Patel, Suketu and Murphy, Derek and Haralmbieva, Eugenia and Abdulla, Zainalabideen A. and Wong, Kah Keng and Chen, Hong and Gould, Edith and Roncador, Giovanna and Hatton, Chris S. R. and Anderson, Amanda P. and Banham, Alison H. and Pulford, Karen}, title = {Increased Expression of Phosphorylated FADD in Anaplastic Large Cell and Other T-Cell Lymphomas}, series = {Biomarker Insights}, volume = {9}, journal = {Biomarker Insights}, issn = {1177-2719}, doi = {10.4137/bmi.s16553}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121403}, pages = {77-84}, year = {2014}, abstract = {FAS-associated protein with death domain (FADD) is a major adaptor protein involved in extrinsic apoptosis, embryogenesis, and lymphocyte homeostasis. Although abnormalities of the FADD/death receptor apoptotic pathways have been established in tumorigenesis, fewer studies have analyzed the expression and role of phosphorylated FADD (pFADD). Our identification of FADD as a lymphoma-associated autoantigen in T-cell lymphoma patients raises the possibility that pFADD, with its correlation with cell cycle, may possess role(s) in human T-cell lymphoma development. This immunohistochemical study investigated pFADD protein expression in a range of normal tissues and lymphomas, particularly T-cell lymphomas that require improved therapies. Whereas pFADD was expressed only in scattered normal T cells, it was detected at high levels in T-cell lymphomas (eg, 84\% anaplastic large cell lymphoma and 65\% peripheral T cell lymphomas, not otherwise specified). The increased expression of pFADD supports further study of its clinical relevance and role in lymphomagenesis, highlighting phosphorylation of FADD as a potential therapeutic target.}, language = {en} } @article{BuderMuellerBeekmannetal.2014, author = {Buder, Kristina and M{\"u}ller, Philip A. and Beekmann, Gabriele and Ugurel, Selma and Br{\"o}cker, Eva-Bettina and Becker, J{\"u}rgen C.}, title = {Denileukin Diftitox plus Total Skin Electron Beam Radiation in Patients with Treatment-refractory Cutaneous T-cell Lymphoma (Mycosis Fungoides): Report of Four Cases}, series = {Acta Dermato-Venereologica}, volume = {94}, journal = {Acta Dermato-Venereologica}, doi = {10.2340/00015555-1627}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-120091}, pages = {94-96}, year = {2014}, abstract = {Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma (CTCL) (1). Most patients initially respond well to standard therapy, but advanced MF is often treatment refractory. Thus, a combination of the available treatment options is an important strategy. Total skin electron beam radiation (TSEB) is effective in MF, with a complete remission rate of up to 90\% in the early stages. However, in patients with more advanced stages, remission rates are considerably lower (2, 3). Denileukin diftitox (DD) (Ontak®) is a recombinant fusion protein of the receptor-binding domain of interleukin (IL)-2 and the enzymatic and translocation domains of diphtheria toxin (4). It targets the alpha-subunit of the IL-2-receptor (CD25). There are no reports on this combination therapy in MF.}, language = {en} } @article{ZugmaierToppAlekaretal.2014, author = {Zugmaier, G. and Topp, M. S. and Alekar, S. and Viardot, A. and Horst, H.-A. and Neumann, S. and Stelljes, M. and Bargou, R. C. and Goebeler, M. and Wessiepe, D. and Degenhard, E. and Goekbuget, N. and Klinger, M.}, title = {Long-term follow-up of serum immunoglobulin levels in blinatumomab-treated patients with minimal residual disease-positive B-precursor acute lymphoblastic leukemia}, series = {Blood Cancer Journal}, volume = {4}, journal = {Blood Cancer Journal}, number = {e244}, issn = {2044-5385}, doi = {10.1038/bcj.2014.64}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-115433}, year = {2014}, abstract = {No abstract available.}, language = {en} } @article{GrafLiHerrmannetal.2014, author = {Graf, Nicolas and Li, Zhoulei and Herrmann, Ken and Weh, Daniel and Aichler, Michaela and Slawska, Jolanta and Walch, Axel and Peschel, Christian and Schwaiger, Markus and Buck, Andreas K. and Dechow, Tobias and Keller, Ulrich}, title = {Positron emission tomographic monitoring of dual phosphatidylinositol-3-kinase and mTOR inhibition in anaplastic large cell lymphoma}, series = {Oncotargets and Therapy}, volume = {7}, journal = {Oncotargets and Therapy}, doi = {10.2147/OTT.S59314}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-117915}, pages = {789-798}, year = {2014}, abstract = {Background: Dual phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibition offers an attractive therapeutic strategy in anaplastic large cell lymphoma depending on oncogenic nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) signaling. We tested the efficacy of a novel dual PI3K/mTOR inhibitor, NVP-BGT226 (BGT226), in two anaplastic large cell lymphoma cell lines in vitro and in vivo and performed an early response evaluation with positron emission tomography (PET) imaging using the standard tracer, 2-deoxy-2-[F-18] fluoro-D-glucose (FDG) and the thymidine analog, 3'-deoxy-3'-[F-18] fluorothymidine (FLT). Methods: The biological effects of BGT226 were determined in vitro in the NPM-ALK positive cell lines SU-DHL-1 and Karpas299 by 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay, propidium iodide staining, and biochemical analysis of PI3K and mTOR downstream signaling. FDG-PET and FLT-PET were performed in immunodeficient mice bearing either SU-DHL-1 or Karpas299 xenografts at baseline and 7 days after initiation of treatment with BGT226. Lymphomas were removed for immunohistochemical analysis of proliferation and apoptosis to correlate PET findings with in vivo treatment effects. Results: SU-DHL-1 cells showed sensitivity to BGT226 in vitro, with cell cycle arrest in G0/G1 phase and an IC50 in the low nanomolar range, in contrast with Karpas299 cells, which were mainly resistant to BGT226. In vivo, both FDG-PET and FLT-PET discriminated sensitive from resistant lymphoma, as indicated by a significant reduction of tumor-to-background ratios on day 7 in treated SU-DHL-1 lymphoma-bearing animals compared with the control group, but not in animals with Karpas299 xenografts. Imaging results correlated with a marked decrease in the proliferation marker Ki67, and a slight increase in the apoptotic marker, cleaved caspase 3, as revealed by immunostaining of explanted lymphoma tissue. Conclusion: Dual PI3K/mTOR inhibition using BGT226 is effective in ALK-positive anaplastic large cell lymphoma and can be monitored with both FDG-PET and FLT-PET early on in the course of therapy.}, language = {en} } @article{vonBernuthRavindranDuetal.2014, author = {von Bernuth, Horst and Ravindran, Ethiraj and Du, Hang and Froehler, Sebastian and Strehl, Karoline and Kraemer, Nadine and Issa-Jahns, Lina and Amulic, Borko and Ninnemann, Olaf and Xiao, Mei-Sheng and Eirich, Katharina and Koelsch, Uwe and Hauptmann, Kathrin and John, Rainer and Schindler, Detlev and Wahn, Volker and Chen, Wei and Kaindl, Angela M.}, title = {Combined immunodeficiency develops with age in Immunodeficiency-centromeric instability-facial anomalies syndrome 2 (ICF2)}, series = {Orphanet Journal of Rare Dieeases}, volume = {9}, journal = {Orphanet Journal of Rare Dieeases}, doi = {10.1186/s13023-014-0116-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-114859}, pages = {116}, year = {2014}, abstract = {The autosomal recessive immunodeficiency-centromeric instability-facial anomalies syndrome (ICF) is characterized by immunodeficiency, developmental delay, and facial anomalies. ICF2, caused by biallelic ZBTB24 gene mutations, is acknowledged primarily as an isolated B-cell defect. Here, we extend the phenotype spectrum by describing, in particular, for the first time the development of a combined immune defect throughout the disease course as well as putative autoimmune phenomena such as granulomatous hepatitis and nephritis. We also demonstrate impaired cell-proliferation and increased cell death of immune and non-immune cells as well as data suggesting a chromosome separation defect in addition to the known chromosome condensation defect.}, language = {en} }