Epstein-Barr virus-associated lymphomas decoded.

Epstein-Barr virus (EBV)-associated lymphomas cover a range of histological B- and T-cell non-Hodgkin and Hodgkin lymphoma subtypes. The role of EBV on B-cell malignant pathogenesis and its impact on the tumour microenvironment are intriguing but incompletely understood. Both the International Consensus Classification (ICC) and 5th Edition of the World Health Organization (WHO-HAEM5) proposals give prominence to the distinct clinical, prognostic, genetic and tumour microenvironmental features of EBV in lymphoproliferative disorders. There have been major advances in our biological understanding, in how to harness features of EBV and its host immune response for targeted therapy, and in using EBV as a method to monitor disease response. In this article, we showcase the latest developments and how they may be integrated to stimulate new and innovative approaches for further lines of investigation and therapy.

Irritable Bowel Syndrome in Veterans with Gulf War Illness Evaluated at VA's War-Related Illness and Injury Study Center.

INTRODUCTION: Excess rates of Gulf War illness (GWI) and irritable bowel syndrome (IBS), two chronic multisymptom illnesses, have long been documented among nearly 700,000 veterans who served in the 1990-1991 Persian Gulf War. We sought to report the prevalence, characteristics, and association of GWI and IBS decades after the war in a clinical cohort of deployed Gulf War veterans (GWVs) who were evaluated at the Department of Veterans Affairs' War Related Illness and Injury Study Center (WRIISC) for unexplained chronic symptoms. MATERIALS AND METHODS: We analyzed data gathered from clinical intake questionnaires of deployed GWVs who were evaluated at WRIISC clinics between 2008 and 2020. We applied Centers for Disease Control (CDC) criteria to determine the prevalence of severe GWI. IBS was identified using Rome IV diagnostic criteria (current IBS) and veterans' self-reported "history of physician-diagnosed IBS." We examined associations between IBS and GWI using bivariate analyses and multivariable logistic regression. RESULTS: Among the N = 578 GWVs evaluated by the WRIISC, severe GWI (71.8%), history of physician-diagnosed IBS (50.3%) and current IBS (42.2%) were all highly prevalent. Nearly half of GWVs with severe GWI met Rome criteria for IBS (45.8%), and over half reported a history of physician-diagnosed IBS (56.1%). In multivariable models, severe GWI was significantly associated both with current IBS (adjusted odds ratio (aOR): 1.68, 95% CI: 1.11, 2.54) and with veteran-reported history of physician-diagnosed IBS (aOR: 2.15, 95% CI: 1.43, 2.23). IBS with diarrhea (IBS-D) was the most common subtype among GWVs with current IBS (61.1%). However, IBS-mixed affected a significantly greater proportion of veterans with severe GWI, compared to veterans who did not have severe GWI (P = .03). CONCLUSIONS: More than 20 years after the Persian Gulf War, our findings indicate a high degree of comorbidity between severe GWI and IBS among deployed GWVs seeking care for unexplained illnesses. Our results suggest GWVs with GWI should be screened for IBS for which evidence-based treatments are available and could potentially reduce symptom burden. Conversely, symptoms of IBS should trigger additional evaluation for non-gastrointestinal symptoms in deployed Gulf War veterans to identify possible GWI and ensure a comprehensive approach to care.

Longitudinal Patterns of Multimorbidity in Gulf War Era Veterans With and Without Gulf War Illness.

Objectives: To examine whether severe Gulf War illness (SGWI) case status was associated with longitudinal multimorbidity patterns. Methods: Participants were users of the Veteran Health Administration Health Care System drawn from the Gulf War Era Cohort and Biorepository (n = 840). Longitudinal measures of multimorbidity were constructed using (1) electronic health records (Charlson Comorbidity Index; Elixhauser; and Veterans Affairs Frailty Index) from 10/1/1999 to 6/30/2023 and (2) self-reported medical conditions (Deficit Accumulation Index) since the war until the survey date. Accelerated failure time models examined SGWI case status as a predictor of time until threshold level of multimorbidity was reached, adjusted for age and sociodemographic and military characteristics. Results: Models, adjusted for covariates, revealed that (1) relative to the SWGI- group, the SGWI+ group was associated with an accelerated time for reaching each threshold and (2) the relationship between SGWI and each threshold was not moderated by age. Discussion: Findings suggest that veterans with SGWI experienced accelerated aging.

Brexucabtagene autoleucel for relapsed or refractory mantle cell lymphoma in the United Kingdom: A real-world intention-to-treat analysis.

Brexucabtagene autoleucel (brexu-cel) is an autologous CD19 CAR T-cell product, approved for relapsed/refractory (r/r) mantle cell lymphoma (MCL). In ZUMA-2, brexu-cel demonstrated impressive responses in patients failing ≥2 lines, including a bruton's tyrosine kinase inhibitor, with an overall and complete response rate of 93% and 67%, respectively. Here, we report our real-world intention-to-treat (ITT) outcomes for brexu-cel in consecutive, prospectively approved patients, from 12 institutions in the United Kingdom between February 2021 and June 2023, with a focus on feasibility, efficacy, and tolerability. Of 119 approved, 104 underwent leukapheresis and 83 received a brexu-cel infusion. Progressive disease (PD) and/or manufacturing (MF) were the most common reasons for failure to reach harvest and/or infusion. For infused patients, best overall and complete response rates were 87% and 81%, respectively. At a median follow-up of 13.3 months, median progression-free survival (PFS) for infused patients was 21 months (10.1-NA) with a 6- and 12-month PFS of 82% (95% confidence interval [CI], 71-89) and 62% (95% CI, 49-73), respectively. ≥Grade 3 cytokine release syndrome and neurotoxicity occurred in 12% and 22%, respectively. On multivariate analysis, inferior PFS was associated with male sex, bulky disease, ECOG PS > 1 and previous MF. Cumulative incidence of non-relapse mortality (NRM) was 6%, 15%, and 25% at 6, 12, and 24 months, respectively, and mostly attributable to infection. Outcomes for infused patients in the UK are comparable to ZUMA-2 and other real-world reports. However, ITT analysis highlights a significant dropout due to PD and/or MF. NRM events warrant further attention.