Multi-modal analysis reveals tumor and immune features distinguishing EBV-positive and EBV-negative post-transplant lymphoproliferative disorders.

The oncogenic Epstein-Barr virus (EBV) can drive tumorigenesis with disrupted host immunity, causing malignancies including post-transplant lymphoproliferative disorders (PTLDs). PTLD can also arise in the absence of EBV, but the biological differences underlying EBV(+) and EBV(-) B cell PTLD and the associated host-EBV-tumor interactions remain poorly understood. Here, we reveal the core differences between EBV(+) and EBV(-) PTLD, characterized by increased expression of genes related to immune processes or DNA interactions, respectively, and the augmented ability of EBV(+) PTLD B cells to modulate the tumor microenvironment through elaboration of monocyte-attracting cytokines/chemokines.

International Metabolic Prognostic Index Is Superior to Other Metabolic Tumor Volume-Based Prognostication Methods in a Real-Life Cohort of Diffuse Large B-Cell Lymphoma.

Baseline metabolic tumor volume (MTV) is a promising prognostic marker in diffuse large B-cell lymphoma (DLBCL). We assessed the prognostic value of 4 novel metabolic risk scores in a real-life DLBCL cohort and compared them with the revised International Prognostic Index (IPI). We included a consecutive series of untreated DLBCL, not otherwise specified cases that were diagnosed in our hospital from 2008 to 2021 with available baseline [F]FDG PET/CT.

Genetic and immunological features of immune deficiency and dysregulation-associated lymphoproliferations and lymphomas as a basis for classification.

Immune deficiency and dysregulation-associated lymphoproliferative disorders and lymphomas (IDD-LPDs) encompass a heterogeneous clinical and pathological spectrum of disorders that range from indolent lymphoproliferations to aggressive lymphomas. They arise in a variety of clinical settings and are associated with oncogenic viruses such as the Epstein-Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus/human herpes virus (KSHV/HHV8) in some, but not all, cases. The recognition of IDD-LPDs as distinct from LPDs in immune competent patients is essential to tailor clinical management options for affected patients.

Clinical characteristics and survival outcomes of patients with primary central nervous system lymphoma treated with high-dose methotrexate-based polychemotherapy and consolidation therapies.

Given the rarity of primary central nervous system lymphoma (PCNSL), evaluations of different high-dose methotrexate-(HD-MTX)-based treatment regimens is sparse. This retrospective, multicenter study evaluates clinical characteristics and outcomes (progression-free, overall and disease-specific survival) after five HD-MTX-based polychemotherapeutic regimens and two consolidation therapies. 346 patients with histologically confirmed PCNSL, treated with ≥ 1 cycle HD-MTX-based strategies (≥3g/m/cycle) were included.

Single center, real-world retrospective study of CAR-T cell therapy for relapsed/refractory large B-cell lymphoma beyond second line: five-year results at the University Hospitals Leuven.

Introduction: Large B-cell lymphomas (LBCL) are the most frequently aggressive B-cell non-Hodgkin lymphomas. Anti-CD19 chimeric antigen receptor (CAR)-T cell therapy has emerged as a new, powerful treatment for relapsed or refractory (R/R) disease. Two CAR-T cell products, tisagenlecleucel (tisa-cel,) and axicabtagene ciloleucel (axi-cel), are reimbursed in Belgium for R/R LBCL beyond second line.

Single center, real-world retrospective study of CAR-T cell therapy for relapsed/refractory large B-cell lymphoma beyond second line: five-year results at the University Hospitals Leuven.

Introduction: Large B-cell lymphomas (LBCL) are the most frequently aggressive B-cell non-Hodgkin lymphomas. Anti-CD19 chimeric antigen receptor (CAR)-T cell therapy has emerged as a new, powerful treatment for relapsed or refractory (R/R) disease. Two CAR-T cell products, tisagenlecleucel (tisa-cel,) and axicabtagene ciloleucel (axi-cel), are reimbursed in Belgium for R/R LBCL beyond second line.

Treatment of Epstein-Barr Virus infection in immunocompromised patients.

Epstein-Barr Virus (EBV), is a ubiquitous γ-Herpesvirus that infects over 95% of the human population and can establish a life-long infection without causing any clinical symptoms in healthy individuals by residing in memory B-cells. Primary infection occurs in childhood and is mostly asymptomatic, however in some young adults it can result in infectious mononucleosis (IM). In immunocompromised individuals however, EBV infection has been associated with many different malignancies.

Tabelecleucel for allogeneic haematopoietic stem-cell or solid organ transplant recipients with Epstein-Barr virus-positive post-transplant lymphoproliferative disease after failure of rituximab or rituximab and chemotherapy (ALLELE): a phase 3, multicentre, open-label trial.

Background: Survival in Epstein-Barr virus (EBV)-positive post-transplant lymphoproliferative disease following haematopoietic stem-cell transplant (HSCT) or solid organ transplant (SOT) is poor after failure of initial therapy, indicating an urgent need for therapies for this ultra-rare disease. With recent EU marketing authorisation, tabelecleucel is the first off-the-shelf, allogeneic, EBV-specific T-cell immunotherapy to receive approval for treatment of relapsed or refractory EBV-positive post-transplant lymphoproliferative disease. We aimed to determine the clinical benefit of tabelecleucel in patients with relapsed or refractory EBV-positive post-transplant lymphoproliferative disease following HSCT or SOT.

OpenFIBSEM: A universal API for FIBSEM control.

This paper introduces OpenFIBSEM, a universal API to control Focused Ion Beam Scanning Electron Microscopes (FIBSEM). OpenFIBSEM aims to improve the programmability and automation of electron microscopy workflows in structural biology research. The API is designed to be cross-platform, composable, and extendable: allowing users to use any portion of OpenFIBSEM to develop or integrate with other software tools.

Epidemiology, Outcomes, and Complement Gene Variants in Secondary Thrombotic Microangiopathies.

Background: The identification of complement defects as major drivers of primary atypical hemolytic uremic syndrome (HUS) has transformed the landscape of thrombotic microangiopathies (TMAs), leading to the development of targeted therapies and better patient outcomes. By contrast, little is known about the presentation, genetics, and outcomes of TMA associated with specific diseases or conditions, also referred to as secondary TMA.

Methods: In this study, we assessed the relative incidence, clinical and genetic spectra, and long-term outcomes of secondary TMA versus other TMAs in consecutive patients hospitalized with a first episode of TMA from 2009 to 2019 at two European reference centers.

Safety and performance of the Spectra Optia apheresis system for white blood cell depletion in patients with elevated white blood cell counts.

Background: For the past 30 years, white blood cell depletion (WBCD) or leukocytapheresis has been conducted to rapidly reduce excessive circulating white blood cell (WBC) concentrations in patients at risk for or with symptoms of leukostasis due to hyperleukocytosis. The goal of leukocytapheresis is to prevent or treat acute complications from leukostasis, thereby enabling patients to receive potentially curative chemotherapy.

Methods: This report details the results from a retrospective and a prospective clinical study conducted in the European Union and the People's Republic of China, which assessed the use of the Spectra Optia Apheresis System for leukocytapheresis in patients with hyperleukocytosis.

Characteristics and Outcome of Post-Transplant Lymphoproliferative Disorders After Solid Organ Transplantation: A Single Center Experience of 196 Patients Over 30 Years.

Post-transplant lymphoproliferative disorder (PTLD) is a rare but life-threatening complication after transplantation. In this retrospective, monocentric study we aimed to collect real life data regarding PTLD and determine the role of Epstein Barr Virus (EBV) status and year of diagnosis on prognosis. We identified 196 biopsy-proven PTLD after solid organ transplantation (SOT) diagnosed at the University Hospitals Leuven (Belgium) from 1989 to 2019.

[F]FDG-PET/CT volumetric parameters can predict outcome in untreated mantle cell lymphoma.

Several studies have shown a strong predictive value for pretreatment [F]FDG-PET/CT metabolic parameters in different lymphoma subtypes. However, few publications exist concerning the role of metabolic parameters in mantle cell lymphoma (MCL). We retrospectively investigated the prognostic value of baseline metabolic tumor volume (MTV) and lesion dissemination in untreated MCL.

Aberrant MYCN expression drives oncogenic hijacking of EZH2 as a transcriptional activator in peripheral T-cell lymphoma.

Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of hematological cancers arising from the malignant transformation of mature T cells. In a cohort of 28 PTCL cases, we identified recurrent overexpression of MYCN, a member of the MYC family of oncogenic transcription factors. Approximately half of all PTCL cases was characterized by a MYC expression signature.

Epstein-Barr virus-associated posttransplant lymphoproliferative disorders: new insights in pathogenesis, classification and treatment.

Purpose Of Review: Posttransplant lymphoproliferative disorder (PTLD) is a serious complication following transplantation from an allogeneic donor. Epstein-Barr Virus (EBV) is involved in a substantial number of cases. In this review, we aim to summarize recent knowledge on pathogenesis, classification and treatment of EBV + PTLD.

Evaluating fostamatinib disodium as a treatment option for immune thrombocytopenia in adult patients.

Introduction: Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder characterized by increased platelet destruction and decreased platelet production, leading to thrombocytopenia with or without bleeding manifestations. The majority of patients experiencing treatment need will eventually need secondary treatment following first-line therapy with steroids. In 2018, the oral spleen tyrosine kinase inhibitor fostamatinib received US Food and Drug Administration approval for ITP patients with an insufficient response to a previous treatment.

Pushing the boundaries. Concurrent Hodgkin lymphoma and breast cancer treatment with preservation of pregnancy: A case report.

Background: Breast cancer and hematological cancers are the most commonly diagnosed malignancies during pregnancy. This case report is the first to describe the ultimate challenge to preserve a pregnancy while the expectant mother is diagnosed and treated simultaneously for two concurrent primary malignancies, a stage IIA Hodgkin lymphoma and pT2N0(Sn) breast cancer.

Clinical Case: A 36-year-old pregnant primigravida underwent a routine non-invasive prenatal test at 14 weeks and 4 days of gestation.

Immunotherapy for cancer treatment during pregnancy.

Immunotherapy has greatly improved outcomes for subgroups of patients with cancer. As indications keep expanding, there is an unmet need to gain a better understanding of the effect of these therapies on pregnancy and fertility. During pregnancy, substantial adaptations occur in the maternal immune system to maintain protection against pathogens while avoiding detrimental reactions to the semi-allogeneic fetus.

Fusion transcripts FYN-TRAF3IP2 and KHDRBS1-LCK hijack T cell receptor signaling in peripheral T-cell lymphoma, not otherwise specified.

Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of non-Hodgkin lymphomas with poor prognosis. Up to 30% of PTCL lack distinctive features and are classified as PTCL, not otherwise specified (PTCL-NOS). To further improve our understanding of the genetic landscape and biology of PTCL-NOS, we perform RNA-sequencing of 18 cases and validate results in an independent cohort of 37 PTCL cases.

Comprehensive genome-wide analysis of routine non-invasive test data allows cancer prediction: A single-center retrospective analysis of over 85,000 pregnancies.

Background: Implausible false positive results in non-invasive prenatal testing (NIPT) have been occasionally associated with the detection of occult maternal malignancies. Hence, there is a need for approaches allowing accurate prediction of whether the NIPT result is pointing to an underlying malignancy, as well as for organized programs ensuring efficient downstream clinical management of these cases.

Methods: Using a data set of 88,294 NIPT performed at University Hospital Leuven (Belgium) between November 2013 and March 2020, we retrospectively evaluated the positive predictive value (PPV) of our NIPT approach for cancer detection.