Clinical profile and cardiovascular events in patients with atrial fibrillation and hematologic malignancies with recent initiation of targeted therapy: real-life data from CANAC-FA registry.

Background: "Real-life" data on cardiovascular management and clinical outcomes in patients with atrial fibrillation (AF) and hematologic malignancies are limited.

Aim: To describe the clinical profile and incidence of cardiovascular events in this population.

Methods: Data were obtained from the CANAC-FA Registry, an observational, multicenter and retrospective study.

Real-World Treatment Patterns After Discontinuation of Venetoclax or BTKis in the Frontline Setting Among Older Adults With Chronic Lymphocytic Leukemia.

Purpose: Venetoclax and Bruton's tyrosine kinase inhibitors (BTKis) are key treatment options for patients with chronic lymphocytic leukemia (CLL) in the frontline setting. This study characterized postdiscontinuation treatment patterns and hospitalization of frontline venetoclax and BTKis in a national sample of older adults with CLL.

Methods: We identified 1,770 Medicare beneficiaries 66 years and older with CLL initiating venetoclax with obinutuzumab (VEN-O, n = 193) or BTKi treatment (n = 1,577) in the frontline setting between June 01, 2019, and June 30, 2020.

EXPRESSION OF IMMUNOGLOBULIN LIGHT CHAIN GENES IN STEREOTYPED CASES FROM UKRAINIAN COHORT OF CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS.

Background: Analysis of immunoglobulin heavy chain gene (IGHV) rearrangements expressed in chronic lymphocytic leukemia (CLL) cells has provided insights into the B-cell receptor (BCR) repertoire in CLL. In more than 40% of CLL patients, (quasi)identical or stereotyped BCR is expressed. The recent data point at the non-stochastic expression of immunoglobulin light lambda (IGLV) or kappa (IGKV) chains as well.

Potassium/sodium cation carriers robustly up-regulate CD20 antigen by targeting MYC, and synergize with anti-CD20 immunotherapies to eliminate malignant B cells.

Our investigation uncovers that nanomolar concentrations of salinomycin, monensin, nigericin, and narasin (a group of potassium/sodium cation carriers) robustly enhance surface expression of CD20 antigen in B-cell-derived tumor cells, including primary malignant cells of chronic lymphocytic leukemia and diffuse large B-cell lymphoma. Experiments in vitro, ex vivo, and animal model reveal a novel approach of combining salinomycin or monensin with therapeutic anti-CD20 monoclonal antibodies or anti-CD20 CAR-T cells, significantly improving non- Hodgkin lymphoma (NHL) therapy. The results of RNA-seq, genetic editing, and chemical inhibition delineate the molecular mechanism of CD20 upregulation, at least partially, to the downregulation of MYC, the transcriptional repressor of the MS4A1 gene encoding CD20.

The survival grip-how cell adhesion promotes tumor maintenance within the microenvironment.

Cell adhesion is warranted by proteins that are crucial for the maintenance of tissue integrity and homeostasis. Most of these proteins behave as receptors to link adhesion to the control of cell survival and their expression or regulation are often altered in cancers. B-cell malignancies do not evade this principle as they are sustained in relapsed niches by interacting with the microenvironment that includes cells and their secreted factors.

Clonally unrelated HL-type RS manifested as hemophagocytic syndrome: a case report and literature review.

Hodgkin lymphoma variant of Richter syndrome (HL-type RS) is a very rare disease, in which chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) is transformed into novel Hodgkin lymphoma. The most important prognostic factor of HL-type RS is the clonal relationship between HL-type RS and the preexisting CLL/SLL. Detailed confirmation of clonally unrelated HL-type RS cases have not been reported.

Case report: HSV lymphadenitis in immunocompromised patient with CLL.

Background: Richter's transformation (RT) in chronic lymphocytic leukemia (CLL) is associated with poor prognosis and requires prompt modifications in patient care. CLL patients are susceptible to severe infections due to immune dysregulation induced by their malignancy and immunosuppressive therapies.

Case Presentation: We present a case of a 63-year-old man with CLL who previously achieved remission and presented with a right inguinal mass.

A 16-week progressive exercise training intervention in treatment-naïve chronic lymphocytic leukaemia: a randomised-controlled pilot study.

Background: Chronic lymphocytic leukaemia (CLL) typically presents with asymptomatic, early-stage disease that is monitored until disease progression ('treatment-naïve' CLL). The objective of this pilot study was to assess the feasibility and preliminary safety of an exercise program in treatment-naïve CLL. We also sought to preliminarily assess the impact of the exercise program on disease activity, as it has been proposed that exercise training may reduce disease outgrowth in treatment-naïve CLL.

A Practical Guideline for MicroRNA Sequencing Data Analysis in Chronic Lymphocytic Leukemia.

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression. They have been associated with several diseases and cancers, including chronic lymphocytic leukemia (CLL). CLL is the most common form of adult leukemia, and its pathogenesis is driven by the deletion of miRNAs, such as the miR-15a/16-1 cluster.

Transcriptomic clustering of chronic lymphocytic leukemia: molecular subtypes based on Bruton's tyrosine kinase expression levels.

Historically, CLL prognostication relied on disease burden, reflected in clinical stage. Later, chromosome abnormalities and genomics suggested several CLL subtypes which were aligned with response to therapy. Gene expression profiling data identified pathways associated with CLL progression.

Clinical and Paraclinical Characterizations, Management, and Prognosis in DPPX Antibody-Associated Encephalitis: A Systematic Review.

In dipeptidyl-peptidase-like protein 6 (DPPX) antibody-associated encephalitis, DPPX antibodies from serum and CSF target the extracellular subunit of the voltage-gated potassium channel 4.2. This targeting leads to a characteristic clinical triad comprising gastrointestinal symptoms (predominantly diarrhea), cognitive-psychiatric dysfunction, and manifestations of CNS hyperexcitability, with hyperekplexia being a more specific feature.

Proliferating CLL cells express high levels of CXCR4 and CD5.

Chronic lymphocytic leukemia (CLL) is an incurable progressive malignancy of CD5 B cells with a birth rate between 0.1% and 1% of the entire clone per day. However, the phenotype and functional characteristics of proliferating CLL cells remain incompletely understood.

Establishing meaningful change thresholds for European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire CLL-specific module domain scores: An analysis based on the TRANSCEND CLL 004 study in patients with relapsed or refractory chronic lymphocytic leukaemia or small lymphocytic lymphoma.

Introduction: The study aimed to establish meaningful thresholds at patient and group levels for the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire CLL-specific module (EORTC QLQ-CLL17) domain scores in adults with relapsed or refractory (R/R) chronic lymphocytic leukaemia (CLL).

Material And Methods: Data for the analysis were from the TRANSCEND CLL 004 study (NCT03331198). EORTC QLQ-CLL17 and selected anchor measures were assessed at baseline and multiple postbaseline visits up to 24 months after treatment initiation.

Emergence of rearrangement and mutations in , , and associated with therapy resistance in chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is an indolent low-grade B-cell neoplasm that generally responds well to treatment. Rarely, CLL cases exhibit an IGH::CCND1 rearrangement, presenting a diagnostic challenge in distinguishing between clonal evolution within CLL and an independent mantle cell lymphoma. We report a case of CLL with the emergence of an IGH::CCND1 rearrangement and mutations associated with treatment resistance, including TP53, BTK, and BCL2, during disease progression.

Immunoglobulin light chain mutational status refines IGHV prognostic value in identifying chronic lymphocytic leukemia patients with early treatment requirement.

The mutational status of immunoglobulin (IG) light chain genes in chronic lymphocytic leukemia (CLL) and its clinical impact have not been extensively studied. To assess their prognostic significance, the IG light chain gene repertoire in CLL patients has been evaluated using a training-validation approach. In the training cohort (N = 573 CLL), 92.

Single-cell analysis of a bi-clonal chronic lymphocytic leukemia reveals two clones with distinct gene expression pattern.

Dual productive B-cell receptor (BCR) rearrangements have been repeatedly reported for chronic lymphocytic leukemia (CLL), but the standard population-based PCR analyses cannot distinguish whether these are bi-clonal CLL, or a monoclonal CLL with bi-allelic productive rearrangements. We investigated CLL cells by combined single-cell RNA and BCR sequencing. We identified two CLL clones using different immunoglobulin (Ig) heavy-chain V region genes (IGHV) genes and distinct Ig λ light chains.

Liposomal Encapsulation of Chlorambucil with a Terpyridine-Based, Glutathione-Targeted Optical Probe Facilitates Cell Entry and Cancer Cell Death.

The nitrogen mustard alkylating agent chlorambucil (CBL) is a critical component of chemotherapeutic regimens used in the treatment of chronic lymphocytic leukemia. The cancer cell-killing actions of CBL are limited by glutathione (GSH) conjugation, a process catalyzed by the GSH transferase hGSTA1-1 that triggers CBL efflux from cells. In the cancer cell microenvironment, intracellular GSH levels are elevated to counterbalance oxidative stress generated due to the high glycolytic demand.

Differential Cardiotoxicity of Ibrutinib Versus Chemoimmunotherapy in Chronic Lymphocytic Leukemia: A Population-Based Study.

Chronic lymphocytic leukaemia (CLL) is the most common form of leukaemia among adults, particularly in Western nations. The introduction of Bruton's tyrosine kinase (BTK) inhibitors as a treatment of CLL, namely, ibrutinib, which is a first-generation BTK inhibitor, has significantly improved the treatment landscape for CLL. However, ibrutinib has been associated with an increased risk of atrial fibrillation (AF) and hypertension.

Inflammatory Markers Significantly Increased in Patients Treated with Obinotuzumab for Lymphoproliferative Diseases.

: The purpose of this study was to analyze the behaviors of inflammatory markers, such as procalcitonin and C-reactive protein (CRP), during treatment with obinotuzumab (an anti-CD20 antibody). : Our non-randomized observational study prospectively evaluated a cohort of 22 adult patients with lymphoproliferative neoplasms, chronic lymphocytic leukemia (CLL), and follicular lymphoma (FL) with indications for obinotuzumab therapy. : All patients had their blood drawn to determine blood counts, CRP, and procalcitonin, as well as body temperature measurements and blood cultures performed for bacterial infections on day 0 before administration of the anti-CD20 antibody.

Somatic Recombination Between an Ancient and a Recent Gene Variant Is Associated with the NOTCH2 Gain-of-Function Phenotype in Chronic Lymphocytic Leukemia.

Constitutively active NOTCH2 signaling is a hallmark in chronic lymphocytic leukemia (CLL). The precise underlying defect remains obscure. Here we show that the mRNA sequence coding for the NOTCH2 negative regulatory region (NRR) is consistently deleted in CLL cells.

Molecular Composition and Kinetics of B Cells During Ibrutinib Treatment in Patients with Chronic Lymphocytic Leukemia.

Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of B cells due to constitutive B-cell receptor (BCR) signaling, leading to apoptosis resistance and increased proliferation. This study evaluates the effects of the Bruton Tyrosine Kinase (BTK) inhibitor ibrutinib on the molecular composition, clonality, and kinetics of B cells during treatment in CLL patients. Employing a multi-omics approach of up to 3.

Real-World Evidence on Adverse Events and Healthcare Resource Utilization in Patients with Chronic Lymphocytic Leukaemia in Spain Using Natural Language Processing: The SRealCLL Study.

The SRealCLL study described the occurrence of adverse events (AEs) and healthcare resource utilization in patients with chronic lymphocytic leukaemia (CLL) using artificial intelligence in a real-world scenario in Spain. We collected real-world data on patients with CLL from seven Spanish hospitals between January 2016 and December 2018, focusing on their AE and healthcare service utilization. Data extraction from electronic health records of 385,904 patients was performed using the EHRead technology, which is based on natural language processing and machine learning.