CD19-directed chimeric antigen receptor T-cell therapy: what can we learn from the haematologist?

CD19-directed chimeric antigen receptor (CAR) T-cell therapy, originally developed for haematological malignancies, has recently emerged as a promising therapy for patients with autoimmune diseases. By selectively depleting CD19-positive B-cells, this therapy brings a new approach in resetting immune dysregulation and potentially providing long-term remission for patients with a refractory disease. Recent reports have highlighted its effectiveness in conditions such as SLE, systemic sclerosis and myositis.

Targeting DOT1L and EZH2 synergizes in breaking the germinal center identity of Diffuse Large B-cell Lymphoma.

Differentiation of antigen-activated B cells into pro-proliferative germinal center (GC) B cells depends on the activity of the transcription factors MYC and BCL6, and the epigenetic writers DOT1L and EZH2. GCB-like Diffuse Large B Cell Lymphomas (GCB-DLBCLs) arise from GCB cells and closely resemble their cell of origin. Given the dependency of GCB cells on DOT1L and EZH2, we investigated the role of these epigenetic regulators in GCB-DLBCLs and observed that GCB-DLBCLs synergistically depend on the combined activity of DOT1L and EZH2.

Groundwater arsenic and antimony mobility from an antimony mining area: Controls of sulfide oxidation, carbonate and silicate weathering, and secondary mineral precipitation.

Sulfide mineral oxidation has been recognized as the key driver of arsenic (As) and antimony (Sb) mobility in mining-impacted groundwater. However, the role of carbonate and silicate weathering and secondary mineral precipitation in this process remain unknown. A comprehensive geochemical study of groundwater was conducted in an Sb-mining area, Hunan, China, with samples collected from aquifers of the Xikuangshan Formation (Dx), the Shetianqiao Formation (Ds ), and the Lower Carboniferous Formation (Cy).

Enteropathy-associated T-cell lymphoma: A population-based cohort study on incidence, treatment, and outcome in the Netherlands.

Introduction: Enteropathy-associated T-cell lymphoma (EATL) is a peripheral T-cell lymphoma (PTCL) with a poor prognosis. Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with or without etoposide consolidated by autologous stem cell transplantation (ASCT) are recommended for fit PTCL patients. The role of etoposide and ASCT in EATL is unclear.

Health-related quality of life dynamics: modeling insights from immunotherapy.

Background: Understanding health-related quality of life (HRQoL) dynamics is essential for assessing and improving treatment experiences; however, clinical and observational studies struggle to capture their full complexity. We use simulation modeling and the case of Chimeric Antigen Receptor T-cell therapy-a type of cancer immunotherapy that can prolong survival, but carries life-threatening risks-to study HRQoL dynamics.

Methods: We developed an exploratory system dynamics model with mathematical equations and parameter values informed by literature and expert insights.

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.

Comparative effectiveness of 6x R-CHOP21 versus 6x R-CHOP21 + 2 R for patients with advanced-stage diffuse large B-cell lymphoma.

First-line treatment for advanced-stage diffuse large B-cell lymphoma (DLBCL) typically involves 6x R-CHOP21 or 6x R-CHOP21 with two additional rituximab administrations (6x R-CHOP21 + 2 R). In contemporary practice, this treatment choice might be guided by interim PET scan results. This nationwide, population-based study investigates the comparative effectiveness of these treatment regimens in an era where interim PET-guided treatment decisions were not standard practice.

Rationale and design of RESILIENCE: A prospective randomized clinical trial evaluating remote ischaemic conditioning for the prevention of anthracycline cardiotoxicity.

Aims: There is a lack of therapies able to prevent anthracycline cardiotoxicity (AC). Remote ischaemic conditioning (RIC) has shown beneficial effects in preclinical models of AC.

Methods: REmote iSchemic condItioning in Lymphoma PatIents REceiving ANthraCyclinEs (RESILIENCE) is a multinational, prospective, phase II, double-blind, sham-controlled, randomized clinical trial that evaluates the efficacy and safety of RIC in lymphoma patients receiving anthracyclines.

Size-Increased All-Phenylene Molecular Spoked Wheels - A Combined Theoretical and Experimental Approach.

A lateral expansion of molecular spoked wheels (MSWs) based on an all-phenylene backbone is described. The MSWs contain a central hub, six spokes, and a rim that is formed by a sixfold Yamamoto coupling of the respective non-cyclized dodecabromo precursor yielding MSWs with up to 30 phenylene rings in the perimeter. Attempts to prepare compounds of such size without flexible side groups at the spokes were unsuccessful, most probably due to an aggregation and accompanying oligomerization of the precursors during the cyclization.

Groundwater irrigation induced variations in DOM fluorescence and arsenic mobility.

Dissolved organic matter (DOM) plays a predominant role in groundwater arsenic (As) mobility. However, the temporal-spatial variations in DOM fluorescent characteristics and their effects on As mobility induced by groundwater irrigation remain unclear. To address these issues, groundwater from multilevel and irrigation wells in Zones I and II (with low- and high-As groundwater irrigation, respectively) from the Hetao Basin, China, were monitored in both non-irrigation (NIG) and irrigation (IG) seasons.

Impact of debulking therapy on the clinical outcomes of axicabtagene ciloleucel in the treatment of relapsed or refractory large B-cell lymphoma.

Axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor T-cell therapy, was approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL) based on the results from pivotal Cohorts 1+2 of ZUMA-1 (NCT02348216). ZUMA-1 was expanded to investigate safety management strategies aimed at reducing the incidence and severity of cytokine release syndrome (CRS) and neurologic events (NEs). Prospective safety expansion Cohort 5 evaluated the impact of debulking therapy, including rituximab-containing immunochemotherapy regimens and radiotherapy, in axi-cel-treated patients; the CRS and NE management strategy paralleled those in Cohorts 1+2.

Production and stability of cultured red blood cells depends on the concentration of cholesterol in culture medium.

The production of cultured red blood cells (cRBC) for transfusion purposes requires large scale cultures and downstream processes to purify enucleated cRBC. The membrane composition, and cholesterol content in particular, are important during proliferation of (pro)erythroblasts and for cRBC quality. Therefore, we tested the requirement for cholesterol in the culture medium during expansion and differentiation of erythroid cultures with respect to proliferation, enucleation and purification by filtration.

para-Aminoazobenzenes-Bipolar Redox-Active Molecules.

Azobenzenes (ABs) are versatile compounds featured in numerous applications for energy storage systems, such as solar thermal storages or phase change materials. Additionally, the reversible one-electron reduction of these diazenes to the nitrogen-based radical anion has been used in battery applications. Although the oxidation of ABs is normally irreversible, 4,4'-diamino substitution allows a reversible 2e oxidation, which is attributed to the formation of a stable bis-quinoidal structure.

Same job, same working conditions? A cross-sectional study to examine the similarities and differences of the working situation in ambulatory and residential youth welfare workers.

Background: Employees in social work exhibit high rates of sick leave due to mental health issues. Additionally, work-related demands in youth welfare have increased in recent years. Particularly in light of the escalating shortage of skilled professionals in this field, this trend becomes especially critical.

Treatment strategies and outcome in relapsed peripheral T-cell lymphoma: results from the Netherlands Cancer Registry.

Optimal treatment in patients with refractory or relapsed peripheral T-cell lymphomas (R/R T-NHLs) is unknown. In this population-based study, outcomes in R/R peripheral T-cell lymphoma not otherwise specified (PTCL NOS), angioimmunoblastic T-cell lymphoma (AITL), and anaplastic lymphoma kinase-positive (ALK+) and ALK-negative (ALK-) anaplastic large cell lymphoma (ALCL) were evaluated. Patients with PTCL NOS, AITL, ALK+ ALCL, and ALK- ALCL (≥18 years) diagnosed in 2014 to 2019 were identified using the Netherlands Cancer Registry.

Brentuximab vedotin and chemotherapy in relapsed/refractory Hodgkin lymphoma: a propensity score-matched analysis.

Several single-arm studies have explored the inclusion of brentuximab vedotin (BV) in salvage chemotherapy followed by autologous stem cell transplantation (ASCT) for relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL). However, no head-to-head comparisons with standard salvage chemotherapy have been performed. This study presents a propensity score-matched analysis encompassing individual patient data from 10 clinical trials to evaluate the impact of BV in transplant-eligible patients with R/R cHL.