Publications by authors named "Michael Von Bergwelt-Baildon"

Article Synopsis
  • Tixagevimab-cilgavimab is effective in reducing severe COVID-19 outcomes in high-risk hematological malignancy patients during the Omicron wave, despite a significant incidence of breakthrough infections.
  • 32.6% of patients experienced COVID-19 infections, but most cases were milder and shorter in duration, especially within the first six months of treatment.
  • Recent B-cell depletion was identified as a significant risk factor for breakthrough infections, indicating that these patients may need extra caution and monitoring.
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Tertiary lymphoid structures (TLS) in cancer are considered ectopic hotspots for immune activation that are similar to lymphoid follicles in secondary lymphoid organs (SLO). This study elucidates shared and TLS/SLO-specific features in pancreatic ductal adenocarcinoma (PDAC). TLS abundance was related to superior survival and T-cell abundance in 110 treatment-naïve PDAC samples, underlining their clinical relevance.

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Article Synopsis
  • CAR T cell therapy has transformed the treatment of blood cancers, but long-term survivors face significant challenges like infections, second cancers, and non-relapse mortality.
  • Infections are the primary cause of non-relapse mortality, often related to weakened immune systems following treatment, while secondary primary malignancies have raised concerns, leading to FDA warnings.
  • Effective management of these complications, including preventive measures and monitoring, is essential for enhancing patient outcomes as CAR T therapy is explored for broader applications beyond cancer.
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Prostate cancer (PCa) metastasis is one of the leading causes of cancer-related mortality in men worldwide, primarily due to its tendency to metastasize, with bones of axial skeleton being the favored target-site. PCa bone-metastasis (PCa-BM) presents significant clinical challenges, especially by the weakening of bone architecture, majorly due to the formation of osteoblastic lesions, leading to severe bone fractures. Another complication is that the disease predominantly affects elderly men.

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Approximately one third of the German population has a migration background.According to the federal office for migration, in 2022 around 2,7 million people have taken refuge or have immigrated to Germany, causing major challenges for our health system. In this article, important infectious diseases, and non-infectious conditions like hemoglobinopathies are presented.

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Objectives: The treatment of rare tumors often necessitates the involvement of highly specialized teams, typically based in larger medical centers or university hospitals, which are often lacking in rural areas. The German TARGET (the Trans-sectoral Personalized Care Concept for Patients with Rare Cancers) project aims to improve the network between outpatient oncology practices and more centralized expert teams via telemedicine.

Methods: The primary work involved conceptualizing the implementation of project requirements based on feedback from various TARGET project teams, and ultimately, the method of implementation using the software CentraXX.

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Article Synopsis
  • The introduction highlights the rapid growth of point-of-care (POC) manufacturing for chimeric antigen receptor (CAR) modified T cells, particularly focusing on anti-CD20 CAR T cells for melanoma patients in a phase I clinical trial.
  • The methods used involved producing CD20 CAR T cells using a second-generation lentiviral vector on the CliniMACS Prodigy® platform, demonstrating high purity and functionality across two production sites.
  • Results confirmed a sufficient expansion and activation capability of the CAR T cells, revealing interindividual differences in their response, thereby supporting the effectiveness of the CliniMACS Prodigy® for decentralized CAR T cell manufacturing.
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The case of a 33-year-old male with recurrent icterus and hemolysis since childhood that was long mistaken for Gilbert disease is presented. Subsequently, the patient also developed splenomegaly and gallstones together with iron overload. Genetic testing revealed the diagnosis of hereditary xerocytosis, which is an erythrocyte membrane disorder causing recurrent hemolysis.

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Relapse and regimen-related toxicities remain major challenges in achieving long-term survival, particularly among older patients with high-risk myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Previous studies have demonstrated the feasibility of treosulfan-based conditioning, noting stable engraftment and low non-relapse mortality (NRM) in patients undergoing HLA-matched allo-HSCT. However, data on treosulfan-based conditioning in the HLA-haploidentical transplantation (HaploT) setting are limited.

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Purpose: This study investigates the care provision and the role of infectious disease (ID) specialists during the coronavirus disease-2019 (COVID-19) pandemic.

Methods: A survey was conducted at German study sites participating in the Lean European Open Survey on SARS-CoV-2 infected patients (LEOSS). Hospitals certified by the German Society of Infectious diseases (DGI) were identified as ID centers.

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Chimeric antigen receptor T cell therapy has been established in the treatment of various B cell malignancies. However, translating this therapeutic effect to treat solid tumors has been challenging because of their inter-tumoral as well as intratumoral heterogeneity and immunosuppressive microenvironment. Local interventions, such as surgery, radiotherapy, local ablation, and locoregional drug delivery, can enhance chimeric antigen receptor T cell therapy in solid tumors by improving tumor infiltration and reducing systemic toxicities.

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Although chimeric antigen receptor (CAR) T cell therapy represents a transformative immunotherapy, it is also associated with distinct toxicities that contribute to morbidity and mortality. In this systematic review and meta-analysis, we searched MEDLINE, Embase and CINAHL (Cochrane) for reports of nonrelapse mortality (NRM) after CAR T cell therapy in lymphoma and multiple myeloma up to March 2024. After extraction of causes and numbers of death, we analyzed NRM point estimates using random-effect models.

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Purpose: To assess the eligibility of patients with advanced or recurrent solid malignancies presented to a molecular tumor board (MTB) at a large precision oncology center for inclusion in trials with the endpoints objective response rate (ORR) or duration of response (DOR) based on Response Evaluation Criteria in Solid Tumors (RECIST version 1.1).

Methods: Prospective patients with available imaging at the time of presentation in the MTB were included.

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Cancer immunotherapy with chimeric antigen receptor (CAR) T cells can cause immune effector cell-associated neurotoxicity syndrome (ICANS). However, the molecular mechanisms leading to ICANS are not well understood. Here we examined the role of microglia using mouse models and cohorts of individuals with ICANS.

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Article Synopsis
  • * Neurocognitive testing (NCT) revealed mild impairments in some patients, while brain imaging (BI) showed abnormalities in only 14.5% of cases, suggesting that the changes may not be directly linked to COVID-19 effects.
  • * Patients with severe CS were more likely to experience symptoms of depression, fatigue, and a lower quality of life, indicating a potential connection between cognitive symptoms and overall mental health issues among Post COVID-19 patients.
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Systemic sclerosis, a severe inflammatory autoimmune disease, shares a common thread with cancer through the underlying mechanism of inflammation. This inflammatory milieu not only drives the immune dysregulation characteristic of autoimmune diseases but also plays a pivotal role in the pathogenesis of cancer. Among the cellular components involved, B cells have emerged as key players in hematologic tumor and autoimmune disease, contributing to immune dysregulation and persistent tissue fibrosis in systemic sclerosis, as well as tumor progression and immune evasion in cancer.

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Background: The individual HLA-I genotype is associated with cancer, autoimmune diseases and infections. This study elucidates the role of germline homozygosity or allelic imbalance of HLA-I loci in esophago-gastric adenocarcinoma (EGA) and determines the resulting repertoires of potentially immunogenic peptides.

Methods: HLA genotypes and sequences of either (1) 10 relevant tumor-associated antigens (TAAs) or (2) patient-specific mutation-associated neoantigens (MANAs) were used to predict good-affinity binders using an in silico approach for MHC-binding (www.

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Article Synopsis
  • In the context of multiple myeloma, CAR T cells targeting B cell maturation antigen (BCMA) show promise for long-term disease management, with various constructs being tested for efficacy.* -
  • The study explored the impact of different CAR designs, specifically varying linker lengths and costimulatory domains, on the performance of anti-BCMA CAR T cells using primary T cells and myeloma cell lines.* -
  • Results indicated that while the short linker CAR had better cytokine production, the CD28-based CARs outperformed in cytotoxicity and faster killing of MM cells, but the 41BB-based CARs exhibited better persistence in vivo, highlighting the complexity of optimizing CAR architectures.*
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Purpose: Brain metastasis (BM) in colorectal cancer (CRC) is a rare event with poor prognosis. Apart from (K)RAS status and lung and bone metastasis no biomarkers exist to identify patients at risk. This study aimed to identify a gene expression signature associated with colorectal BM.

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Lymph node metastasis (LNM) occurs in less than 5% of soft tissue sarcoma (STS) patients and indicates an aggressive course of disease. Suspicious lymph nodes (LN) in staging imaging are a frequent topic of discussion in multidisciplinary tumor boards. Predictive markers are needed to facilitate stratification and improve treatment of STS patients.

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Article Synopsis
  • Immunotherapies, especially immune checkpoint inhibitors, are effective against various tumors but often lead to serious side effects that need thorough analysis to improve patient outcomes.
  • The international Side-Effect Registry Immuno-Oncology (SERIO) collects detailed data on side effects from immunotherapy across different tumor types, focusing on immune-related adverse events (irAE) and integrating new modules for specific syndromes.
  • With 1398 documented irAE cases from 58 centers in 13 countries, SERIO has provided valuable insights into the prevalence and severity of these side effects, contributing to numerous publications aimed at improving management strategies for patients experiencing these adverse events.
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Background: Treatment of hematological malignancies with chimeric antigen receptor modified T cells (CART) is highly efficient, but often limited by an immune effector cell-associated neurotoxicity syndrome (ICANS). As conventional MRI is often unremarkable during ICANS, we aimed to examine whether resting-state functional MRI (rsfMRI) is suitable to depict and quantify brain network alterations underlying ICANS in the individual patient.

Methods: The dysconnectivity index (DCI) based on rsfMRI was longitudinally assessed in systemic lymphoma patients and 1 melanoma patient during ICANS and before or after clinical resolution of ICANS.

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