Observations from a national sample exchange program for molecular haematology testing.

External quality assessment programs (EQAP) for molecular haematology generally only assess the analytical phase of laboratory testing or provide limited evaluation of post-analytical components. We incorporated comprehensive post-analytical evaluation into an existing national inter-laboratory sample exchange program for molecular haematology due to the increasing complexity of diagnostic molecular testing and interpretation. We report key findings from four years of longitudinal data using this approach.

Gene Expression Signatures for the Accurate Diagnosis of Peripheral T-Cell Lymphoma Entities in the Routine Clinical Practice.

Purpose: Peripheral T-cell lymphoma (PTCL) includes heterogeneous clinicopathologic entities with numerous diagnostic and treatment challenges. We previously defined robust transcriptomic signatures that distinguish common PTCL entities and identified two novel biologic and prognostic PTCL-not otherwise specified subtypes (PTCL-TBX21 and PTCL-GATA3). We aimed to consolidate a gene expression-based subclassification using formalin-fixed, paraffin-embedded (FFPE) tissues to improve the accuracy and precision in PTCL diagnosis.

Characterisation of immune checkpoints in Richter syndrome identifies LAG3 as a potential therapeutic target.

Richter syndrome (RS), an aggressive lymphoma occurring in the context of chronic lymphocytic leukaemia/small lymphocytic lymphoma, is associated with poor prognosis when treated with conventional immunochemotherapy, therefore, improved treatments are required. Immune checkpoint blockade has shown efficacy in some B-cell malignancies and modest responses in early clinical trials for RS. We investigated the immune checkpoint profile of RS as a basis to inform rational therapeutic investigations in RS.

LAG3: a novel immune checkpoint expressed by multiple lymphocyte subsets in diffuse large B-cell lymphoma.

Blockade of the PD-1 axis has modest efficacy in diffuse large B-cell lymphoma (DLBCL), but data regarding LAG3 are sparse. The impact of LAG3 digital gene expression was tested in 309 patients with DLBCL treated with standard chemoimmunotherapy. Cellular distribution of LAG3 protein was determined by immunohistochemistry and flow cytometry.

COO and MYC/BCL2 status do not predict outcome among patients with stage I/II DLBCL: a retrospective multicenter study.

In advanced-stage diffuse large B-cell lymphoma (DLBCL), the presence of an activated B-cell phenotype or a non-germinal center (GCB) phenotype, coexpression of MYC and BCL2 by immunohistochemistry, and the cooccurrence of and or rearrangements are associated with inferior outcomes. It is unclear whether these variables remain prognostic in stage I/II patients. In this retrospective study, we evaluated the prognostic impact of cell of origin (COO), as well as dual-expressor (DE) status and molecular double-hit (DH) status, in stage I/II DLBCL by positron emission tomography with computed tomography (PET-CT).

The tumour microenvironment is immuno-tolerogenic and a principal determinant of patient outcome in EBV-positive diffuse large B-cell lymphoma.

Objective: Epstein-Barr virus-positive diffuse large B-cell lymphoma (EBV DLBCL) is a recently identified entity. Data regarding outcome to frontline immuno-chemotherapy are conflicting. Although the prognostic impact of the tumour microenvironment (TME) in EBV DLBCL is well-established, it remains untested whether the TME influences survival in EBV DLBCL.

Circulating cell-free miR-494 and miR-21 are disease response biomarkers associated with interim-positron emission tomography response in patients with diffuse large B-cell lymphoma.

MicroRNA (miRNA)s are dysregulated in Diffuse large B-cell lymphoma (DLBCL), where they reflect the malignant B-cells and the immune infiltrate within the tumor microenvironment. There remains a paucity of data in DLBCL regarding cell-free (c-f) miRNA as disease response biomarkers. Immunosuppressive monocyte/macrophages, which are enriched in DLBCL, are disease response markers in DLBCL, with miRNA key regulators of their immunosuppressive function.

Immune evasion via PD-1/PD-L1 on NK cells and monocyte/macrophages is more prominent in Hodgkin lymphoma than DLBCL.

Much focus has been on the interaction of programmed cell death ligand 1 (PD-L1) on malignant B cells with programmed cell death 1 (PD-1) on effector T cells in inhibiting antilymphoma immunity. We sought to establish the contribution of natural killer (NK) cells and inhibitory CD163 monocytes/macrophages in Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL). Levels of PD-1 on NK cells were elevated in cHL relative to DLBCL.

The T-cell Receptor Repertoire Influences the Tumor Microenvironment and Is Associated with Survival in Aggressive B-cell Lymphoma.

To investigate the relationship between the intra-tumoral T-cell receptor (TCR) repertoire and the tumor microenvironment (TME) in diffuse large B-cell lymphoma (DLBCL) and the impact of TCR on survival. We performed high-throughput unbiased TCRβ sequencing on a population-based cohort of 92 patients with DLBCL treated with conventional (i.e.

Ratios of T-cell immune effectors and checkpoint molecules as prognostic biomarkers in diffuse large B-cell lymphoma: a population-based study.

Background: Risk-stratification of diffuse large B-cell lymphoma (DLBCL) requires identification of patients with disease that is not cured, despite initial treatment with R-CHOP. The prognostic importance of the revised International Prognostic Index (R-IPI) and cell of origin of the malignant B cell are established in DLBCL. We aimed to develop a novel, easily applicable, tissue-based prognostic biomarker based on quantification of the tumour microenvironment that is independent of and additive to the R-IPI and cell of origin.

Predictors of poor outcome and benefits from antibiotics in children with acute otitis media: pragmatic randomised trial.

Objectives: To identify which children with acute otitis media are at risk of poor outcome and to assess benefit from antibiotics in these children.

Design: Secondary analysis of randomised controlled trial cohort.

Setting: Primary care.