Publications by authors named "Stephen M Ansell"

Background: CD19 CAR T-cell therapy is a novel anti-cancer treatment that has produced remarkable responses in relapsed or refractory B-cell hematological malignancies. Cytokine Release Syndrome (CRS) is a dysregulated immune response that frequently occurs after CAR T-cell infusion. It can cause cardiac dysfunction and circulatory collapse negatively impacting outcomes and survival.

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The role of the bone marrow (BM) microenvironment in regulating the antitumor immune response in Waldenstrom macroglobulinemia (WM) remains poorly understood. Here we transcriptionally and phenotypically profiled non-malignant (CD19 CD138) BM cells from WM patients with a focus on myeloid derived suppressive cells (MDSCs) to provide a deeper understanding of their role in WM. We found that HLA-DRCD11bCD33 MDSCs were significantly increased in WM patients as compared to normal controls, with an expansion of predominantly polymorphonuclear (PMN)-MDSCs.

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Recent breakthroughs in research have sparked a paradigm shift in our understanding of cancer biology, uncovering the critical role of the crosstalk between tumor cells and the immune cells of the tumor microenvironment (TME) in malignant transformation. Fibroblasts have long been viewed as ancillary participants in cancer progression, often eclipsed by the prominence given to malignant cells. Novel investigations, however, have increasingly acknowledged the essential part played by the fibroblasts and their phenotypic doppelganger cancer-associated fibroblasts (CAFs) in fostering immunosuppression and promoting tumor progression.

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Background And Objectives: Patients with typical anti-myelin-associated glycoprotein (anti-MAG) neuropathy have IgM-gammopathy, mimic distal chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and are treatment resistant. Anti-MAG patients go unrecognized when IgM-gammopathy is undetected or with atypical phenotypes. We investigated an optimal anti-MAG titration cutoff for excluding CIDP and the impact of IgM-gammopathy detection on neuropathy treatment evaluation without anti-MAG antibodies.

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This study sheds light on the pivotal role of the oncoprotein DEK in B-cell lymphoma. We reveal DEK expression correlates with increased tumor proliferation and inferior overall survival in cases diagnosed with low-grade B-cell lymphoma (LGBCL). We also found significant correlation between DEK expression and copy number alterations in LGBCL tumors, highlighting a novel mechanism of LGBCL pathogenesis that warrants additional exploration.

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Disease Overview: Hodgkin lymphoma (HL) is an uncommon B-cell lymphoid malignancy affecting 8570 new patients annually and representing ~10% of all lymphomas in the United States.

Diagnosis: HL is composed of two distinct disease entities: classical HL and nodular lymphocyte predominant HL (also called nodular lymphocyte predominant B-cell lymphoma). Nodular sclerosis, mixed cellularity, lymphocyte depletion, and lymphocyte-rich HL are subgroups of classical HL.

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The infusion autograft absolute number of inhibitory killer immunoglobulin-like receptor (KIR) 2DL2 and activating natural killer (NK)p30 cells are predictors of clinical outcomes in lymphoma patients undergoing autologous peripheral blood hematopoietic stem cell transplantation (APBHSCT). To assess if the long-term recovery of these NK cell subsets still holds clinical relevance, we set up to investigate their prognostic ability at day 100 post-APBHSCT. This was a retrospective single-institution study including 107 patients from our prior phase III trial who had a clinical assessment at day 100 post-APBHSCT.

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Article Synopsis
  • Immunochemotherapy is currently the primary treatment for newly diagnosed diffuse large B-cell lymphoma (ndDLBCL), but it's ineffective for some patients, prompting research into better prognostic methods.
  • By analyzing transcriptomic data from a large group of patients, researchers identified seven distinct clusters of ndDLBCL, with one specific cluster (A7) linked to poorer outcomes due to characteristics like low immune cell presence and high MYC expression.
  • The study also explores how certain drugs, like lenalidomide, may improve treatment for the high-risk A7 cluster by enhancing T-cell movement into tumors and the expression of key tumor markers, while identifying TCF4 as a crucial factor in MYC biology for this group.
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Unirradiated patients with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (NHL) who undergo anti-CD19 chimeric antigen receptor T-cell therapy (CART) have a predominant localized pattern of relapse, the significance of which is heightened in individuals with limited/localized disease before CART. This study reports on the outcomes of patients with R/R NHL and limited (<5 involved sites) disease bridged with or without radiotherapy. A multicenter retrospective review of 150 patients with R/R NHL who received CART with <5 disease sites before leukapheresis was performed.

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Article Synopsis
  • The standard treatment for fit patients with relapsed diffuse large B-cell lymphoma (DLBCL) is salvage chemotherapy followed by autologous stem cell transplant (ASCT), but it may not be ideal for everyone.
  • A study of 151 patients showed that while most had good responses before ASCT, those who had multiple lines of salvage chemotherapy or were diagnosed at an advanced stage faced significantly worse outcomes.
  • Median progression-free survival was 54.5 months and overall survival was 88.9 months, with no significant survival difference based on age or other characteristics, although advanced-stage relapse and multiple salvage treatments negatively affected survival rates.
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Currently, the role of DNA methylation in the immunoglobulin M (IgM) monoclonal gammopathy disease spectrum remains poorly understood. In the present study, a multiomics prospective analysis was conducted integrating DNA methylation, RNA sequencing (RNA-seq), and whole-exome sequencing data in 34 subjects (23 with Waldenström macroglobulinemia [WM], 6 with IgM monoclonal gammopathy of undetermined significance [MGUS], and 5 normal controls). Analysis was focused on defining differences between IgM gammopathies (WM/IgM-MGUS) compared with controls, and specifically between WM and IgM-MGUS.

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Article Synopsis
  • * Findings showed a high overall objective response rate (>75%) with the use of brentuximab vedotin in conjunction with either ipilimumab or nivolumab, indicating effective treatment options for patients.
  • * Identified specific immune markers in the blood that correlate with treatment resistance, which could help in tailoring patient treatment plans for those with treatment-resistant relapsed HL.
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  • * Researchers used a multiomic approach on tumor samples from 444 newly diagnosed DLBCL patients, combining gene analysis methods to identify a signature predictive of high early clinical failure risk.
  • * The study found that this signature, which includes ARID1A mutations, accurately predicted 45% of early clinical failures and could significantly influence future treatment strategies.
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  • Tumor immune infiltration and blood immune signatures are important for predicting outcomes in breast cancer, but their link to response from neoadjuvant chemotherapy (NAC) hasn't been well studied.
  • In a study of 126 breast cancer patients, various immune cell populations in their blood were analyzed to determine if these profiles could predict how well patients would respond to NAC.
  • The findings indicated that specific immune cell types (like myeloid cells in triple-negative and T cells in hormone receptor-positive breast cancer) correlated with treatment responses, while those in HER2-positive cancer showed no significant associations.
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Article Synopsis
  • * Core signal transduction pathways in cHL are often aberrant or constantly activated, largely due to genetic mutations that disrupt normal cellular functions.
  • * Advancements in understanding cHL's biology have led to better treatments, and continued research may uncover new mechanisms that can further inform treatment options in the future.
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Article Synopsis
  • The study focuses on the prognosis of patients with Waldenström macroglobulinemia (WM) and reassesses traditional prognostic scoring systems in light of new therapies and genetic data.
  • Researchers analyzed records of 889 treatment-naïve WM patients to identify clinical predictors influencing overall survival, leading to a new prognostic model based on factors like age and serum levels.
  • The newly developed Modified Staging System for WM (MSS-WM) successfully categorizes patients into four distinct risk groups based on their clinical data, demonstrating significant differences in 5-year overall survival rates.
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Follicular lymphoma (FL) is an indolent non-Hodgkin lymphoma of germinal center origin, which presents with significant biologic and clinical heterogeneity. Using RNA-seq on B cells sorted from 87 FL biopsies, combined with machine-learning approaches, we identify 3 transcriptional states that divide the biological ontology of FL B cells into inflamed, proliferative, and chromatin-modifying states, with relationship to prior GC B cell phenotypes. When integrated with whole-exome sequencing and immune profiling, we find that each state was associated with a combination of mutations in chromatin modifiers, copy-number alterations to TNFAIP3, and T follicular helper cells (Tfh) cell interactions, or primarily by a microenvironment rich in activated T cells.

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Antibody titers and the potential need for immunization have not been formally studied in recipients of chimeric antigen receptor T cell therapy (CAR-T). Prior studies have shown that CD19-targeted CAR-T can induce persistent B cell aplasia but preserve plasma cells for humoral response. Aiming to assess the immune repertoire and antibody titer status of CAR-T recipients, we conducted a retrospective study of immune cell recovery and antibody titers to vaccines in anti-CD19 CAR-T recipients at Mayo Clinic, Rochester.

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Chimeric antigen receptor T-cell therapy is the new standard of care in fit patients with refractory or early relapsed diffuse large B-cell lymphoma (DLBCL). However, there may still be a role for salvage chemotherapy (ST) and autologous stem cell transplant (ASCT) in certain circumstances (e.g.

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Immune checkpoint inhibitors (ICIs) have demonstrated remarkable response rates in relapsed or refractory Hodgkin lymphoma (HL). Still, most patients eventually progress. Patterns of progression after ICIs are not well described and are essential to defining the role of local therapies in combination with ICIs.

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