18 results on '"Merz H"'
Search Results
2. P1233: PRIMARY REFRACTORY PLASMABLASTIC LYMPHOMA: A PRECISION ONCOLOGY APPROACH
- Author
-
Witte, H., primary, Fähnrich, A., additional, Riedl, J., additional, Kuenstner, A., additional, Hertel, N., additional, von Bubnoff, N., additional, Merz, H., additional, Busch, H., additional, Feller, A., additional, and Gebauer, N., additional
- Published
- 2022
- Full Text
- View/download PDF
3. P1232: PRINCIPLES OF PRECISION ONCOLOGY IN PRIMARY REFRACTORY HIGH-GRADE B-CELL LYMPHOMA WITH MYC-, BCL2 AND/OR BCL6 REARRANGEMENTS (HGBL-DH/TH)
- Author
-
Witte, H., primary, Faehnrich, A., additional, Riedl, J., additional, Kuenstner, A., additional, Ketzer, J., additional, von Bubnoff, N., additional, Merz, H., additional, Busch, H., additional, Feller, A., additional, and Gebauer, N., additional
- Published
- 2022
- Full Text
- View/download PDF
4. Clonal evolution and blastic plasmacytoid dendritic cell neoplasm: malignancies of divergent hematopoietic lineages emerging from a common founding clone.
- Author
-
Denker S, Künstner A, Schwarting J, Witte HM, Bernard V, Stölting S, Lohneis P, Kusch K, von Bubnoff N, Merz H, Busch H, Feller AC, and Gebauer N
- Subjects
- Humans, Cell Lineage genetics, Male, Middle Aged, Female, Dendritic Cells pathology, Clonal Evolution genetics, Hematologic Neoplasms pathology, Hematologic Neoplasms genetics
- Published
- 2024
- Full Text
- View/download PDF
5. Radiation-Induced DNA Damage in Uveal Melanoma Is Influenced by Dose Delivery and Chromosome 3 Status.
- Author
-
Tura A, Zhu Y, Vardanyan S, Prasuhn M, Kakkassery V, Lüke J, Merz H, Paulsen F, Rades D, Cremers F, Bartz-Schmidt KU, and Grisanti S
- Subjects
- Humans, Female, Male, Middle Aged, Aged, Adult, Aged, 80 and over, In Situ Hybridization, Fluorescence, In Situ Nick-End Labeling, Radiotherapy Dosage, Immunohistochemistry, Radiosurgery adverse effects, Radiosurgery methods, Dose-Response Relationship, Radiation, Uveal Neoplasms radiotherapy, Uveal Neoplasms genetics, Melanoma radiotherapy, Melanoma genetics, Chromosomes, Human, Pair 3 genetics, DNA Damage
- Abstract
Purpose: The purpose of this study was to analyze the extent of DNA breaks in primary uveal melanoma (UM) with regard to radiotherapy dose delivery (single-dose versus fractionated) and monosomy 3 status., Methods: A total of 54 patients with UM were included. Stereotactic radiotherapy (SRT) was performed in 23 patients, with 8 undergoing single-dose SRT (sdSRT) treatment and 15 receiving fractionated SRT (fSRT). DNA breaks in the enucleated or endoresected tumors were visualized by a TUNEL assay and quantified by measuring the TUNEL-positive area. Protein expression was analyzed by immunohistochemistry. Co-detection of chromosome 3 with proteins was performed by immuno-fluorescent in situ hybridization., Results: The amount of DNA breaks in the total irradiated group was increased by 2.7-fold (P < 0.001) compared to non-irradiated tissue. Tumors treated with fSRT were affected more severely, showing 2.1-fold more DNA damage (P = 0.007) compared to the cases after single (high) dose irradiation (sdSRT). Monosomy 3 tumors showed less DNA breaks compared to disomy 3 samples (P = 0.004). The presence of metastases after radiotherapy correlated with monosomy 3 and less DNA breaks compared to patients with non-metastatic cancer in the combined group with fSRT and sdSRT (P < 0.05)., Conclusions: Fractionated irradiation led to more DNA damage than single-dose treatment in primary UM. As tumors with monosomy 3 showed less DNA breaks than those with disomy 3, this may indicate that they are less radiosensitive, which may influence the efficacy of irradiation.
- Published
- 2024
- Full Text
- View/download PDF
6. Genome-wide DNA methylation-analysis of blastic plasmacytoid dendritic cell neoplasm identifies distinct molecular features.
- Author
-
Künstner A, Schwarting J, Witte HM, Xing P, Bernard V, Stölting S, Lohneis P, Janke F, Salehi M, Chen X, Kusch K, Sültmann H, Chteinberg E, Fischer A, Siebert R, von Bubnoff N, Merz H, Busch H, Feller AC, and Gebauer N
- Subjects
- Humans, Female, Male, Middle Aged, Hematologic Neoplasms genetics, Hematologic Neoplasms pathology, Tumor Microenvironment genetics, Aged, Adult, Prognosis, Gene Expression Regulation, Neoplastic, Mutation, Biomarkers, Tumor genetics, Dendritic Cells pathology, Dendritic Cells metabolism, DNA Methylation
- Abstract
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) constitutes a rare and aggressive malignancy originating from plasmacytoid dendritic cells (pDCs) with a primarily cutaneous tropism followed by dissemination to the bone marrow and other organs. We conducted a genome-wide analysis of the tumor methylome in an extended cohort of 45 BPDCN patients supplemented by WES and RNA-seq as well as ATAC-seq on selected cases. We determined the BPDCN DNA methylation profile and observed a dramatic loss of DNA methylation during malignant transformation from early and mature DCs towards BPDCN. DNA methylation profiles further differentiate between BPDCN, AML, CMML, and T-ALL exhibiting the most striking global demethylation, mitotic stress, and merely localized DNA hypermethylation in BPDCN resulting in pronounced inactivation of tumor suppressor genes by comparison. DNA methylation-based analysis of the tumor microenvironment by MethylCIBERSORT yielded two, prognostically relevant clusters (IC1 and IC2) with specific cellular composition and mutational spectra. Further, the transcriptional subgroups of BPDCN (C1 and C2) differ by DNA methylation signatures in interleukin/inflammatory signaling genes but also by higher transcription factor activity of JAK-STAT and NFkB signaling in C2 in contrast to an EZH2 dependence in C1-BPDCN. Our integrative characterization of BPDCN offers novel molecular insights and potential diagnostic applications., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
7. Detection of Circulating Tumor Cells in Patients with Small Choroidal Melanocytic Lesions.
- Author
-
Grisanti S, Schindler F, Merz H, Kakkassery V, Sonntag SR, and Tura A
- Subjects
- Humans, Retrospective Studies, Biopsy, Neoplastic Cells, Circulating, Melanoma diagnosis, Melanoma genetics
- Abstract
Purpose: To determine the presence of circulating tumor cells (CTCs) in patients with indeterminate small choroidal melanocytic lesions (SCMLs)., Design: Retrospective case series., Participants: Forty-seven patients with choroidal melanocytic lesions 2.5 mm or less in tumor thickness and ≤ 10 mm in largest basal diameter (LBD)., Methods: Blood samples were analyzed for CTCs and the presence of monosomy-3 (M3) in CTCs. Tissue biopsy was performed in the patients who were CTC-positive (pCTC)., Main Outcome Measures: Presence and M3 status of the CTCs with regard to the clinical characteristics and results from tissue biopsy., Results: Median thickness of all (n = 47) lesions was 1.1 mm (range: 0.2-2.5 mm), and LBD was 5.6 mm (range: 2.0-10.0 mm). Circulating tumor cells were found in 25 patients (n = 25). This group was classified as pCTC and compared with the CTC-negative (nCTC) group consisting of 22 patients (n = 22). Median tumor dimensions in the pCTC versus the nCTC group were 1.6 mm (range: 0.6-2.5 mm) versus 0.5 mm (range: 0.2-2.5 mm) for thickness and 6.6 mm (range: 4.1-10.0 mm) versus 4.0 mm (range: 2.0-8.0 mm) for LBD, respectively. Both LBD and thickness were positively associated (P < 0.001) with the presence of CTC. Compared with the nCTC group, a higher percentage of the pCTC group exhibited LBD > 5 mm (36% vs. 88%), subretinal fluid (9.1% vs. 56%), orange pigment (4.5% vs. 60%), sonographic hollowness (9.1% vs. 60%), and the presence of multiple risk factors (0% vs. 68% for ≥3 factors) with P < 0.001 for all parameters. No significant difference was detected in the clinical parameters of the patients who had disomy-3 (D3) (n = 7) versus M3 (n = 17) in their CTC. The tissue biopsy confirmed the uveal melanoma (UM) in 22 of the 25 pCTC patients (88%), whereas no conclusive diagnosis could be determined in the remaining 3 cases because of insufficient or invalid material., Conclusions: We report compelling evidence for the potential of liquid biopsy as an additional tool to screen SCMLs for malignancy. These findings pave the way toward the implementation of liquid biopsy to detect small UM and monitor melanocytic lesions., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
8. Molecularly Stratified Treatment Options in Primary Refractory DLBCL/HGBL with MYC and BCL2 or BCL6 Rearrangements (HGBL, NOS with MYC/BCL6).
- Author
-
Witte HM, Riedl J, Künstner A, Fähnrich A, Ketzer J, Fliedner SMJ, Reimer N, Bernard V, von Bubnoff N, Merz H, Busch H, Feller A, and Gebauer N
- Subjects
- Humans, Proto-Oncogene Proteins c-bcl-6 genetics, Proto-Oncogene Proteins c-myc genetics, B-Lymphocytes, Gene Rearrangement, Proto-Oncogene Proteins c-bcl-2 genetics, Lymphoma, Large B-Cell, Diffuse drug therapy, Lymphoma, Large B-Cell, Diffuse genetics
- Abstract
Background: There is growing evidence supporting multidisciplinary molecular tumor boards (MTB) in solid tumors whereas hematologic malignancies remain underrepresented in this regard., Objective: The present study aimed to assess the clinical relevance of MTBs in primary refractory diffuse large B-cell lymphomas/high-grade B-cell lymphomas with MYC and BCL2 rearrangements (prDLBCL/HGBL-MYC/BCL2) (n = 13) and HGBL, not otherwise specified (NOS), with MYC and BCL6 rearrangements (prHGBL, NOS-MYC/BCL6) (n = 6) based on our previously published whole-exome sequencing (WES) cohort., Patients and Methods: For genomic analysis, the institutional MTB WES pipeline (University Cancer Center Schleswig-Holstein: UCCSH), certified for routine clinical diagnostics, was employed and supplemented by a comprehensive immunohistochemical work-up. Consecutive database research and annotation according to established evidence levels for molecularly stratified therapies was performed (NCT-DKTK/ESCAT)., Results: Molecularly tailored treatment options with NCT-DKTK evidence level of at least m2A were identified in each case. We classified mutations in accordance with biomarker/treatment baskets and detected a heterogeneous spectrum of targetable alterations affecting immune evasion (IE; n = 30), B-cell targets (BCT; n = 26), DNA damage repair (DDR; n = 20), tyrosine kinases (TK; n = 13), cell cycle (CC; n = 7), PI3K-MTOR-AKT pathway (PAM; n = 2), RAF-MEK-ERK cascade (RME; n = 1), and others (OTH; n = 11)., Conclusion: Our virtual MTB approach identified potential molecularly targeted treatment options alongside targetable genomic signatures for both prDLBCL/HGBL-MYC/BCL2 and prHGBL, NOS-MYC/BCL6. These results underline the potential of MTB consultations in difficult-to-treat lymphomas early in the treatment sequence., (© 2023. The Author(s).)
- Published
- 2023
- Full Text
- View/download PDF
9. Primary refractory plasmablastic lymphoma: A precision oncology approach.
- Author
-
Witte HM, Fähnrich A, Künstner A, Riedl J, Fliedner SMJ, Reimer N, Hertel N, von Bubnoff N, Bernard V, Merz H, Busch H, Feller A, and Gebauer N
- Abstract
Introduction: Hematologic malignancies are currently underrepresented in multidisciplinary molecular-tumor-boards (MTB). This study assesses the potential of precision-oncology in primary-refractory plasmablastic-lymphoma (prPBL), a highly lethal blood cancer., Methods: We evaluated clinicopathological and molecular-genetic data of 14 clinically annotated prPBL-patients from initial diagnosis. For this proof-of-concept study, we employed our certified institutional MTB-pipeline (University-Cancer-Center-Schleswig-Holstein, UCCSH) to annotate a comprehensive dataset within the scope of a virtual MTB-setting, ultimately recommending molecularly stratified therapies. Evidence-levels for MTB-recommendations were defined in accordance with the NCT/DKTK and ESCAT criteria., Results: Median age in the cohort was 76.5 years (range 56-91), 78.6% of patients were male, 50% were HIV-positive and clinical outcome was dismal. Comprehensive genomic/transcriptomic analysis revealed potential recommendations of a molecularly stratified treatment option with evidence-levels according to NCT/DKTK of at least m2B/ESCAT of at least IIIA were detected for all 14 prPBL-cases. In addition, immunohistochemical-assessment (CD19/CD30/CD38/CD79B) revealed targeted treatment-recommendations in all 14 cases. Genetic alterations were classified by treatment-baskets proposed by Horak et al. Hereby, we identified tyrosine-kinases (TK; n=4), PI3K-MTOR-AKT-pathway (PAM; n=3), cell-cycle-alterations (CC; n=2), RAF-MEK-ERK-cascade (RME; n=2), immune-evasion (IE; n=2), B-cell-targets (BCT; n=25) and others (OTH; n=4) for targeted treatment-recommendations. The minimum requirement for consideration of a drug within the scope of the study was FDA-fast-track development., Discussion: The presented proof-of-concept study demonstrates the clinical potential of precision-oncology, even in prPBL-patients. Due to the aggressive course of the disease, there is an urgent medical-need for personalized treatment approaches, and this population should be considered for MTB inclusion at the earliest time., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Witte, Fähnrich, Künstner, Riedl, Fliedner, Reimer, Hertel, von Bubnoff, Bernard, Merz, Busch, Feller and Gebauer.)
- Published
- 2023
- Full Text
- View/download PDF
10. Mutational landscape of high-grade B-cell lymphoma with MYC- , BCL2 and/or BCL6 rearrangements characterized by whole-exome sequencing.
- Author
-
Künstner A, Witte HM, Riedl J, Bernard V, Stölting S, Merz H, Olschewski V, Peter W, Ketzer J, Busch Y, Trojok P, Bubnoff NV, Busch H, Feller AC, and Gebauer N
- Subjects
- Gene Rearrangement, Humans, Mutation, Proto-Oncogene Proteins c-bcl-2 genetics, Proto-Oncogene Proteins c-bcl-6 genetics, Proto-Oncogene Proteins c-myc genetics, Exome Sequencing, Lymphoma, Follicular pathology, Lymphoma, Large B-Cell, Diffuse genetics, Lymphoma, Large B-Cell, Diffuse pathology
- Abstract
High-grade B-cell lymphoma accompanied with double/triple-hit MYC and BCL2 and/or BCL6 rearrangements (HGBLDH/ TH) poses a cytogenetically-defined provisional entity among aggressive B-cell lymphomas that is traditionally associated with unfavorable prognosis. In order to better understand the mutational and molecular landscape of HGBLDH/ TH we here performed whole-exome sequencing and deep panel next-generation sequencing of 47 clinically annotated cases. Oncogenic drivers, mutational signatures and perturbed pathways were compared with data from follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL). We find an accumulation of oncogenic mutations in NOTCH, IL6/JAK/STAT and NFκB signaling pathways and delineate the mutational relationship within the continuum between FL/DLBCL, HGBL-DH/TH and BL. Further, we provide evidence of a molecular divergence between BCL2 and BCL6 rearranged HGBL-DH. Beyond a significant congruency with the C3/EZB DLBCL cluster in BCL2 rearranged cases on an exome-wide level, we observe an enrichment of the SBS6 mutation signature in BCL6 rearranged cases. Differential gene set enrichment and subsequent network propagation analysis according to cytogenetically defined subgroups revealed an impairment of TP53 and MYC pathway signaling in BCL2 rearranged cases, whereas BCL6 rearranged cases lacked this enrichment, but instead showed impairment of E2F targets. Intriguingly, HGBL-TH displayed intermediate mutational features considering all three aspects. This study elucidates a recurrent pattern of mutational events driving FL into MYC-driven BCL2-rearranged HGBL, unveiling the mutational pathogenesis of this provisional entity. Through this refinement of the molecular taxonomy for aggressive, germinal center-derived B-cell lymphomas, this calls into question the current World Health Organization classification system, especially regarding the status of MYC/BCL6- rearranged HGBL.
- Published
- 2022
- Full Text
- View/download PDF
11. Integrative molecular profiling identifies two molecularly and clinically distinct subtypes of blastic plasmacytoid dendritic cell neoplasm.
- Author
-
Künstner A, Schwarting J, Witte HM, Bernard V, Stölting S, Kusch K, Nagarathinam K, von Bubnoff N, Murga Penas EM, Merz H, Busch H, Feller AC, and Gebauer N
- Subjects
- Dendritic Cells, Humans, Myeloproliferative Disorders, Skin Neoplasms
- Published
- 2022
- Full Text
- View/download PDF
12. Case Report: GNAQ - and SF3B1 Mutations in an Aggressive Case of Relapsing Uveal Ring Melanoma.
- Author
-
Prasuhn M, Freitag JC, Lüken S, Kakkassery V, Merz H, Caliebe A, Spielmann M, Ranjbar M, and Rommel F
- Abstract
The molecular mechanisms for uveal ring melanoma are still unclear until today. In this case report, we describe a patient with a malignant uveal melanoma with exudative retinal detachment that had been treated with plaque brachytherapy, resulting in successful tumor regression. After 1 year, a ring-shaped recurrence with extraocular extension appeared, and the eye required enucleation. Histological and molecular genetic analyses revealed an epithelioid-cell-type melanoma with complete circumferential involvement of the ciliary body and, so far, unreported GNAQ and SF3B1 mutations in ring melanoma. Therefore, this report gives new genetic background information on this ocular tumor usually leading to enucleation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Prasuhn, Freitag, Lüken, Kakkassery, Merz, Caliebe, Spielmann, Ranjbar and Rommel.)
- Published
- 2022
- Full Text
- View/download PDF
13. Polyclonal Immunotactoid Glomerulopathy Associated with Monoclonal Gammopathy of IgM Type and Underlying Plasmacellular Disease: Successful Treatment with Rituximab Alone.
- Author
-
Neukirchen W, Oesterling A, Wennmann DO, Heitplatz B, Ritter P, Merz H, and Busch V
- Abstract
Immunotactoid glomerulopathy (ITG) occurs infrequently and is characterized by organized IgG containing deposits. It most usually manifests as a concomitant disease of a broad spectrum of oncologic entities. We here present an exceptional case of ITG without glomerular light chain restriction secondary to a IgM kappa type monoclonal gammopathy of undetermined significance. Due to nephrotic syndrome and deterioration of kidney function a rituximab monotherapy was initiated without targeting the plasmacellular augmentation, which was confirmed as the underlying process. The treatment led to a long-term improvement of proteinuria and stabilization of glomerular filtration rate. Its therapeutic effect has to be attributed to immunomodulatory capacities and targeting of podocytes rather than to be interpreted as directed against a bone marrow or glomerular clone. We conclude that rituximab therapy may be a valuable part of the therapeutic options in ITG irrespective of the underlying oncologic entity., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2022 by S. Karger AG, Basel.)
- Published
- 2022
- Full Text
- View/download PDF
14. Comparative analysis of international prognostic indices in gray-zone lymphoma.
- Author
-
Witte HM, Merz H, Bernd HW, Bauer A, Bernard V, Feller AC, and Gebauer N
- Subjects
- Antineoplastic Combined Chemotherapy Protocols therapeutic use, Humans, Prognosis, Progression-Free Survival, Retrospective Studies, Hodgkin Disease diagnosis, Hodgkin Disease therapy, Lymphoma, Large B-Cell, Diffuse drug therapy, Lymphoma, Large B-Cell, Diffuse therapy
- Abstract
Gray-zone lymphoma (GZL) reflects an aggressive B-cell neoplasm with features intermediate between diffuse large B-cell lymphoma (DLBCL) and classical Hodgkin lymphoma (cHL). The International Prognostic Index (IPI) and its derivatives (R-IPI, NCCN-IPI, and the Hasenclever IPS) have been established for DLBCL or cHL while the most suitable scoring system for GZL remains undetermined. In an exploratory multi-centric cohort of GZL ( n = 61), we performed a comparative analysis of prognostic indices with regard to model fit and mutual concordance. The calculation of the corrected Akaike's information criterion (cAIC) and Harrel's concordance index (c-index) for each scoring system identified the NCCN-IPI to harbor the most convincing prognostic capabilities regarding both overall survival (OS) and progression-free survival (PFS) compared to its enhanced derivatives. The current results affirm the clinical utility of the NCCN-IPI and suggest its preferential use in clinical practice in GZL-patients.
- Published
- 2022
- Full Text
- View/download PDF
15. Integrative genomic and transcriptomic analysis in plasmablastic lymphoma identifies disruption of key regulatory pathways.
- Author
-
Witte HM, Künstner A, Hertel N, Bernd HW, Bernard V, Stölting S, Merz H, von Bubnoff N, Busch H, Feller AC, and Gebauer N
- Subjects
- Genomics, Herpesvirus 4, Human genetics, Humans, Proto-Oncogene Proteins c-myc genetics, Signal Transduction, Transcriptome, Epstein-Barr Virus Infections complications, Epstein-Barr Virus Infections genetics, Plasmablastic Lymphoma complications, Plasmablastic Lymphoma diagnosis, Plasmablastic Lymphoma genetics
- Abstract
Plasmablastic lymphoma (PBL) represents a clinically heterogeneous subtype of aggressive B-cell non-Hodgkin lymphoma. Targeted-sequencing studies and a single-center whole-exome sequencing (WES) study in HIV-positive patients recently revealed several genes associated with PBL pathogenesis; however, the global mutational landscape and transcriptional profile of PBL remain elusive. To inform on disease-associated mutational drivers, mutational patterns, and perturbed pathways in HIV-positive and HIV-negative PBL, we performed WES and transcriptome sequencing (RNA-sequencing) of 33 PBL tumors. Integrative analysis of somatic mutations and gene expression profiles was performed to acquire insights into the divergent genotype-phenotype correlation in Epstein-Barr virus-positive (EBV+) and EBV- PBL. We describe a significant accumulation of mutations in the JAK signal transducer and transcription activator (OSMR, STAT3, PIM1, and SOCS1), as well as receptor tyrosine-kinase RAS (ERBB3, NRAS, PDGFRB, and NTRK) pathways. We provide further evidence of frequent perturbances of NF-κB signaling (NFKB2 and BTK). Induced pathways, identified by RNA-sequencing, closely resemble the mutational profile regarding alterations accentuated in interleukin-6/JAK/STAT signaling, NF-κB activity, and MYC signaling. Moreover, class I major histocompatibility complex-mediated antigen processing and cell cycle regulation were significantly affected by EBV status. An almost exclusive upregulation of phosphatidylinositol 3-kinase/AKT/mTOR signaling in EBV+ PBL and a significantly induced expression of NTRK3 in concert with recurrent oncogenic mutations in EBV- PBL hint at a specific therapeutically targetable mechanism in PBL subgroups. Our characterization of a mutational and transcriptomic landscape in PBL, distinct from that of diffuse large B-cell lymphoma and multiple myeloma, substantiates the pathobiological independence of PBL in the spectrum of B-cell malignancies and thereby refines the taxonomy for aggressive lymphomas., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
16. Aggressive B-cell lymphoma cases with 11q aberration patterns indicate a spectrum beyond Burkitt-like lymphoma.
- Author
-
Gebauer N, Witte HM, Merz H, Oschlies I, Klapper W, Caliebe A, Tharun L, Spielmann M, von Bubnoff N, Feller AC, and Murga Penas EM
- Subjects
- Chromosome Aberrations, Humans, In Situ Hybridization, Fluorescence, Burkitt Lymphoma diagnosis, Burkitt Lymphoma genetics, HIV Infections, Lymphoma, B-Cell diagnosis, Lymphoma, B-Cell genetics
- Abstract
The recent characterization of a group of non-MYC rearranged aggressive B-cell lymphomas, resembling Burkitt lymphoma (BL), characteristically harboring a telomeric 11q loss or combined 11q proximal gains/loss pattern has led to the introduction of the provisional entity of Burkitt-like lymphoma with 11q aberration (BLL-11q). Prompted by the discovery of a telomeric 11q loss in an HIV+ high-grade B-cell lymphoma patient, we investigated an extended cohort of aggressive B-cell lymphomas, enriched for cases with histopathological features intermediate between DLBCL and BL, including double- and triple-hit lymphomas (n = 47), for 11q loss/combined 11q proximal gains/loss pattern by fluorescence in situ hybridization. We provide first evidence that 11q aberrations can be found in both BLL in the context of an underlying HIV infection as well as in high-grade B-cell lymphomas with MYC, BCL2, and/or BCL6 rearrangements. We therefore propose that the clinicopathological spectrum of malignancies carrying this aberration may be broader than previously assumed., (© 2021 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
17. Autoimmune neutropenia associated with heterozygous variant of SBDS gene mimicking Shwachman-Bodian-Diamond syndrome.
- Author
-
Rother C, Gebauer N, Schneider J, Bauer A, Holzhausen F, Mayer T, Riecke A, Müller M, Merz H, Steinestel K, and Witte HM
- Subjects
- Humans, Proteins genetics, Shwachman-Diamond Syndrome, Bone Marrow Diseases diagnosis, Bone Marrow Diseases genetics, Neutropenia diagnosis, Neutropenia genetics
- Published
- 2021
- Full Text
- View/download PDF
18. Performance of international prognostic indices in plasmablastic lymphoma: a comparative evaluation.
- Author
-
Hertel N, Merz H, Bernd HW, Bernard V, Künstner A, Busch H, von Bubnoff N, Feller AC, Witte HM, and Gebauer N
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Follow-Up Studies, Humans, International Agencies, Male, Middle Aged, Plasmablastic Lymphoma drug therapy, Prognosis, Retrospective Studies, Risk Factors, Survival Rate, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Nomograms, Plasmablastic Lymphoma pathology
- Abstract
Purpose: Plasmablastic lymphoma (PBL) is a rare and aggressive B-cell malignancy with a heterogenous clinical and prognostic spectrum, determined by multiple factors, including age, HIV- and MYC-status. While there exist several validated scoring systems for diffuse large B-cell lymphoma, which incorporate basic clinical features (age, lactate dehydrogenase, sites of (extranodal) involvement, stage and performance), none of these have been systematically assessed in PBL., Methods: We determined the (age-adjusted; aa)-International Prognostic Index (IPI), revised IPI (R-IPI), and National Comprehensive Cancer Network IPI (NCCN-IPI) in a comprehensive multi-center cohort (n = 78) of PBL patients. Further, all indices were comparatively investigated for model quality and concordance., Results: Univariate analysis revealed significant prognostic capabilities for all indices, all of which identified a subgroup with favorable outcome. Discriminatory power between patients with less benign prognosis and especially refractory disease exhibited significant variability. Subsequently, stratified models for each risk score were compared employing corrected Akaike's information criterion (cAIC) and Harrel's concordance index (c-index). Here, the NCCN-IPI outperformed both IPI and R-IPI regarding c-index with ambiguous cAIC results, underlining its clinical utility and suggesting it for preferential use in clinical practice., Conclusion: Our current observations support the use of the IPI and its enhanced derivatives in PBL patients. There is, however, a distinct requirement for novel prognostic tools to better delineate subgroups at risk for early relapse or refractory disease as well as late relapse. A comprehensive molecular characterization of a clinically annotated cohort of PBL patients is therefore urgently warranted., (© 2021. The Author(s).)
- Published
- 2021
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.