Publications by authors named "David Wrench"

Article Synopsis
  • Posttransplant lymphoproliferative disorder (PTLD) is a rare but serious complication in solid organ transplant patients, and chemotherapy can lead to significant side effects.
  • The TIDaL trial tested the safety and effectiveness of ibrutinib, alongside a risk-based treatment strategy, for newly diagnosed patients with CD20+ B-cell PTLD.
  • While ibrutinib did not meet the effectiveness threshold anticipated, the study highlighted the potential to reduce exposure to harsher chemotherapy treatments for patients in the low-risk category, indicating a direction for future research.
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During the COVID-19 pandemic, ibrutinib with or without rituximab was approved in England for initial treatment of mantle cell lymphoma (MCL) instead of immunochemotherapy. Because limited data are available in this setting, we conducted an observational cohort study evaluating safety and efficacy. Adults receiving ibrutinib with or without rituximab for untreated MCL were evaluated for treatment toxicity, response, and survival, including outcomes in high-risk MCL (TP53 mutation/deletion/p53 overexpression, blastoid/pleomorphic, or Ki67 ≥ 30%).

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Patients with haematological malignancies have a high risk of severe infection and death from SARS-CoV-2. In this prospective observational study, we investigated the impact of cancer type, disease activity, and treatment in 877 unvaccinated UK patients with SARS-CoV-2 infection and active haematological cancer. The primary end-point was all-cause mortality.

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Post-transplant lymphoproliferative disorder (PTLD) is an often fatal complication of cardiac transplantation that occurs in 2% to 6% of transplant recipients. We report a case in which PTLD led to pulmonary artery external compression and multimodality imaging showed key features in the diagnosis, management, and follow-up. ().

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Background: Using an updated dataset with more patients and extended follow-up, we further established cancer patient characteristics associated with COVID-19 death.

Methods: Data on all cancer patients with a positive reverse transcription-polymerase chain reaction swab for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) at Guy's Cancer Centre and King's College Hospital between 29 February and 31 July 2020 was used. Cox proportional hazards regression was performed to identify which factors were associated with COVID-19 mortality.

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Very few studies investigating COVID-19 in cancer patients have included cancer patients as controls. We aimed to identify factors associated with the risk of testing positive for SARS CoV2 infection in a cohort of cancer patients. We analyzed data from all cancer patients swabbed for COVID-19 between 1 March and 31 July 2020 at Guy's Cancer Centre.

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There is insufficient evidence to support clinical decision-making for cancer patients diagnosed with COVID-19 due to the lack of large studies. We used data from a single large UK Cancer Center to assess the demographic/clinical characteristics of 156 cancer patients with a confirmed COVID-19 diagnosis between 29 February and 12 May 2020. Logistic/Cox proportional hazards models were used to identify which demographic and/or clinical characteristics were associated with COVID-19 severity/death.

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Article Synopsis
  • Lymphoplasmacytic lymphoma (LPL) is a rare type of mature B cell lymphoma that typically affects the bone marrow, spleen, and lymph nodes, but can also present as a primary tumor in the stomach, as seen in a case study of a 47-year-old man.
  • The patient displayed reflux symptoms, and investigations revealed a gastroesophageal junction polyp and ulcer, with biopsies indicating an abnormal accumulation of plasma cells and lymphocytes, leading to the diagnosis of primary isolated gastric LPL.
  • This case highlights the uncommon nature of gastric LPL presentations, emphasizing the importance for medical professionals to recognize this rare condition, which may occur without the typical associated paraprotein in serum or significant bone marrow involvement.
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Patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are unfit for or relapsed postautologous stem-cell transplantation have poor outcomes. Historically, mTORC1 inhibitors have produced responses in approximately 30% of patients in this setting. mTORC1 inhibitor efficacy may be limited by resistance mechanisms including AKT activation by mTORC2.

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Background: Consensus guidelines are not available for the use of immunoglobulin replacement therapy (IGRT) in patients developing iatrogenic secondary antibody deficiency following B-cell targeted therapy (BCTT) in autoimmune rheumatic disease.

Objectives: To evaluate the role of IGRT to manage hypogammaglobulinemia following BCTT in autoimmune rheumatic disease (AIRD).

Methods: Using an agreed search string we performed a systematic literature search on Medline with Pubmed as vendor.

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Objectives: The association of B cell targeted therapies with development of hypogammaglobulinaemia and infection is increasingly recognized. Our aim was to develop consensus recommendations for immunoglobulin replacement therapy for management of hypogammaglobulinaemia following B cell targeted therapies in autoimmune rheumatic diseases.

Methods: A modified Delphi exercise involved a 17-member Taskforce committee, consisting of immunologists, rheumatologists, nephrologists, haematologists, a gastroenterologist, an immunology specialist nurse and a patient representative.

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The treatment of relapsed aggressive lymphoma remains a challenge. Platinum-containing chemotherapy is standard of care. Gemcitabine/oxaliplatin (Gem-Ox) with or without rituximab (R) is an outpatient regimen with a favorable toxicity profile.

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Article Synopsis
  • The study looked at how PET scans can help predict outcomes for patients with DLBCL, a type of lymphoma.
  • Researchers found that measuring something called metabolic tumor volume (MTV) before treatment was key in figuring out how well patients would do over time.
  • By combining MTV with another score, they could categorize patients into groups with different chances of survival, helping doctors understand who might need more aggressive treatment.
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Anaemia is an independent, commonly under-recognised risk factor for delirium. Prompt management of anaemia and its underlying aetiology could result in recovery from delirium and associated psychotic manifestations. We report this unprecedented case of complete recovery from delirium and challenging behaviour, following treatment of autoimmune haemolytic anaemia with rituximab.

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Article Synopsis
  • Understanding how Follicular Lymphoma (FL) clones evolve during disease progression is essential for effective treatment and monitoring.
  • Genetic studies suggest FL may evolve through divergent evolution from a common ancestor cell, but it's unclear where this cell is located and how it matures.
  • Analysis of somatic hypermutation in immunoglobulin genes from B cell subpopulations revealed a complex network of distinct tumor subclones, indicating an oligoclonal population stuck in a developmental stage, complicating efforts to find a cure.
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Follicular lymphoma is an incurable malignancy, with transformation to an aggressive subtype representing a critical event during disease progression. Here we performed whole-genome or whole-exome sequencing on 10 follicular lymphoma-transformed follicular lymphoma pairs followed by deep sequencing of 28 genes in an extension cohort, and we report the key events and evolutionary processes governing tumor initiation and transformation. Tumor evolution occurred through either a 'rich' or 'sparse' ancestral common progenitor clone (CPC).

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Inherited risk determinants for follicular lymphoma (FL) have recently been described in the immune gene-rich human leukocyte antigen region on chromosome 6p. The known importance of host immune response to FL survival led us to evaluate these germline factors in FL outcome. We confirm the association of single nucleotide polymorphisms rs10484561 (P = 3.

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Purpose Of Review: Although karyotypic events in follicular lymphoma and its transformation to aggressive lymphoma have been well described, the underlying genetic changes have until recently remained obscure. Both germline and acquired molecular events are now known to predict disease risk and outcome, respectively. Recent developments in these fields are covered within this review.

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To investigate the cell of origin linking follicular (FL) and transformed (t-FL) lymphomas, we analyzed the somatic hypermutation (SHM) pattern of the variable region of the immunoglobulin heavy gene (IgH-VH) in 18 sequential FL/t-FL samples and a father (donor) and son (recipient), who developed FL and t-FL, after transplantation. Genealogic trees showed a pattern compatible with a common progenitor cell (CPC) origin in 13 cases. The identification of the t-FL clonotype in the previous FL sample and of the putative CPC sequence in both the FL/t-FL biopsies showed that the intraclonal diversity of FL and t-FL germinal centers (GCs) is more intricate than previously described, and all 3 clonotypes (CPC, FL, t-FL) may occur simultaneously within the same lymph node.

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