Publications by authors named "Luc Xerri"

A robust prognostic and biological classification for newly diagnosed follicular lymphoma (FL) using molecular profiling remains challenging. FL tumors from patients treated in the RELEVANCE trial with rituximab-chemotherapy (R-chemo) or rituximab-lenalidomide (R2) were analyzed using RNA sequencing, DNA sequencing, immunohistochemistry (IHC), and/or fluorescence in situ hybridization. Unsupervised gene clustering identified 2 gene expression signatures (GSs) enriched in normal memory (MEM) B cells and germinal center (GC) B-cell signals, respectively.

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Introduction: Immune-related neurological syndromes (affecting both the central and peripheral nervous system, as well as the neuromuscular junction) can associate with low-grade B-cell lymphomas.

Methods: We conducted a retrospective study on the records of patients with miscellaneous immune-related neuropathies followed by the "Referral Centre for Neuromuscular Diseases and ALS" in collaboration with the Services of Internal Medicine and Hematology (La Timone Hospital, and the Paoli Calmettes-Insitute, Marseille, France; Geneva University Hospitals, Geneva, Switzerland). Clinical, biological, immunological and histological work-up was carried out and data collected.

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The fifth edition of the World Health Organization Classification of Haematolymphoid Tumours (WHO-HAEM5) is the product of an evidence-based evolution of the revised fourth edition with wide multidisciplinary consultation. Nonetheless, while every classification incorporates scientific advances and aims to improve upon the prior version, medical knowledge remains incomplete and individual neoplasms may not be easily subclassified in a given scheme. Thus, optimal classification requires ongoing study, and there are certain aspects of some entities and subtypes that require further refinements.

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Several therapies to improve the management of lymphoma are currently being investigated, necessitating the development of new biomarkers. However, this requires high-quality and clinically annotated biological material. Therefore, we established a lymphoma biobank including all available biological material (tissue specimens and matched biological resources) along with associated clinical data for lymphoma patients diagnosed, according to the WHO classification, between 2005 and 2022 in the Laboratory of Clinical and Experimental Pathology, Nice, France.

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Article Synopsis
  • Rituximab treatment is more effective than the 'watch and wait' approach for low-tumor burden follicular lymphoma, improving progression-free survival (PFS) but maintenance therapy raised concerns about resource use and patient adherence.
  • A study compared intravenous (IV) rituximab and subcutaneous (SC) rituximab adminstration in patients, demonstrating better 4-year PFS rates in the experimental SC group (58.1% vs 41.2%).
  • While high exposure to rituximab during the first three months led to improved response rates, time to next treatment (TTNT) and overall survival (OS) showed no significant differences between the two approaches.
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  • The RELEVANCE trial compared the effectiveness of lenalidomide plus rituximab (R) to rituximab plus chemotherapy (R-chemo) in patients with untreated advanced-stage follicular lymphoma (FL) over a follow-up period of 6 years.
  • Both treatment groups showed similar 6-year progression-free survival (PFS) rates of about 60% and overall survival rates of 89%, indicating that R is as effective as R-chemo.
  • The study also found no significant safety concerns, suggesting that R is a viable chemo-free option for treating previously untreated patients with FL.
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  • The study investigates biological differences between stage I and stage III/IV follicular lymphoma (FL) by analyzing genomic and immune landscapes through next-generation sequencing and immunohistochemistry.
  • While many similarities in mutations and cell populations were found, notable differences were observed, specifically in the presence of certain T cells and mutations between the stages.
  • The findings suggest that stage I FL shows genetic heterogeneity driven mainly by mutations in STAT6, whereas stage III/IV FL is more influenced by BCL6 translocation, indicating different underlying oncogenic pathways for each stage.
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According to expert guidelines, lymph node surgical excision is the standard of care for lymphoma diagnosis. However, core needle biopsy (CNB) has become widely accepted as part of the lymphoma diagnostic workup over the past decades. The aim of this study was to present the largest multicenter inventory of lymph nodes sampled either by CNB or surgical excision in patients with suspected lymphoma and to compare their diagnostic performance in routine pathologic practice.

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Article Synopsis
  • The overview discusses the upcoming 5th edition of the WHO Classification of Haematolymphoid Tumours, specifically focusing on lymphoid neoplasms, while myeloid and histiocytic neoplasms will be covered separately.
  • Key changes from the previous 4th edition include a hierarchical reorganization of entities, modifications in their nomenclature, and revisions to diagnostic criteria and subtypes.
  • The new edition will also see the deletion of certain entities, the introduction of new ones, and the inclusion of tumour-like lesions and germline predisposition syndromes related to lymphoid neoplasms.
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DUSP22 gene rearrangements are recurrent in systemic and cutaneous ALK-negative anaplastic large cell lymphomas, rarely encountered in other cutaneous CD30+ lymphoproliferations, and typically absent in other peripheral T-cell lymphomas. We report the case of a 51-year-old woman, with longstanding celiac disease and a rapidly enlarging leg ulcer, due to a DUSP22-rearranged CD30+ T-cell lymphoproliferation. Subsequent history revealed an intestinal enteropathy-associated T-cell lymphoma (EATL).

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Despite the impressive efficacy of chimeric antigen receptor (CAR) T-cell therapy (CART) in B-cell non-Hodgkin lymphomas, durable responses are uncommon. The histopathologic and molecular features associated with treatment failure are still largely unknown. Therefore, we have analyzed 19 sequential tumor samples from 9 patients, prior anti-CD19 CART (pre-CART) and at relapse (post-CART), using immunohistochemistry, fluorescence in situ hybridization, array comparative genomic hybridization, next-generation DNA and RNA sequencing, and genome-scale DNA methylation.

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Although follicular lymphoma (FL) is usually graded as FL1-2, FL3A, and FL3B, some borderline cases can be observed and led us to investigate the clinicopathologic diversity of grade 3 FL (FL3). Among 2449 FL patients enrolled in Lymphoma Study Association (LYSA) trials, 1921 cases with sufficient material underwent a central pathologic review. The resulting diagnoses comprised 89.

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In diffuse large B-cell lymphoma (DLBCL), tumor-infiltrating T lymphocytes (TILs) are involved in therapeutic responses. However, tumor-specific TILs can be dysfunctional, with impaired effector functions. Various mechanisms are involved in this exhaustion, and the increased expression of programmed cell death receptor 1 (PD1) and TIM3 on dysfunctional cells suggests their involvement.

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Complete molecular response (CMR) after first-line immunochemotherapy reflects treatment efficacy and may predict prognosis in patients with follicular lymphoma (FL). RELEVANCE is the first phase 3 trial comparing the chemotherapy-free regimen lenalidomide/rituximab (R2) vs rituximab/chemotherapy (R-Chemo) in previously untreated FL patients (ClinicalTrials.gov identifier: NCT01650701).

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Article Synopsis
  • Researchers studied 34 cases of breast implant-associated anaplastic large cell lymphoma (BI-ALCL) to understand the genetic changes that contribute to its development, using advanced sequencing techniques.* -
  • They found that 74% of cases had mutations in epigenetic modifiers, particularly KMT2C and KMT2D, which were linked to changes in specific histone methylation patterns.* -
  • Additionally, mutations in the JAK/STAT signaling pathway were common, especially in tumor samples, suggesting these genetic alterations play a role in the pathology of BI-ALCL.*
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Indolent T-cell lymphoproliferative disorders of the gastrointestinal tract are rare clonal T-cell diseases that more commonly occur in the intestines and have a protracted clinical course. Different immunophenotypic subsets have been described, but the molecular pathogenesis and cell of origin of these lymphocytic proliferations is poorly understood. Hence, we performed targeted next-generation sequencing and comprehensive immunophenotypic analysis of ten indolent T-cell lymphoproliferative disorders of the gastrointestinal tract, which comprised CD4 (n=4), CD8 (n=4), CD4/CD8 (n=1) and CD4/CD8 (n=1) cases.

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Purpose: The PRIMA study (ClinicalTrials.gov identifier: NCT00140582) established that 2 years of rituximab maintenance after first-line immunochemotherapy significantly improved progression-free survival (PFS) in patients with follicular lymphoma compared with observation. Here, we report the final PFS and overall survival (OS) results from the PRIMA study after 9 years of follow-up and provide a final overview of safety.

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