Infectious complications are among the leading causes of mortality in chronic lymphocytic leukemia (CLL). Over the past decade, several advances have been made in treating CLL through inhibition of Bruton tyrosine kinase and the antiapoptotic protein BCL-2. As mortality from CLL progression is expected to decline in the next several years, mortality from severe infections is anticipated to increase. Therefore, understanding the nature of immune defects in CLL and developing strategies to augment the impaired immune system are needed to keep pace with advancements in treatment. This review article summarizes the available data on immune dysfunctions, their clinical consequences, therapeutic implications, and current strategies to enhance immune function in patients with CLL.
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http://dx.doi.org/10.6004/jnccn.2024.7090 | DOI Listing |
Haematologica
March 2025
Experimental Hematology, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain; Department of Medicine, Universitat Autònoma de Barcelona, Bellaterra.
Continuous treatment with ibrutinib not only exerts tumor control but also enhances T cell function in patients with chronic lymphocytic leukemia (CLL). We conducted longitudinal multi-omics analyses in samples from CLL patients receiving ibrutinib upfront to identify potential adaptive mechanisms to Bruton tyrosine kinase (BTK) inhibition during the first 12 months of continuous therapy. We found that ibrutinib induced a decrease in the expression of exhaustion markers and the proportion of Tregs and Tfh cells normalized to levels observed in healthy donors.
View Article and Find Full Text PDFFront Med (Lausanne)
February 2025
Department of Hematology and Oncology, Faculty of Medicine, Augsburg University Hospital, University of Augsburg, Augsburg, Germany.
The treatment landscape for chronic lymphocytic leukemia (CLL) has expanded dramatically over the last decade, with a wide range of effective treatments now available. Clinical management of CLL varies widely depending on patient profile, meaning the optimal treatment in Arab patients, who tend to be young and often present with comorbidities, including diabetes and obesity, requires specific considerations. In the absence of regional guidelines, a group of experts from across the Gulf region and one international expert from Germany convened to discuss and agree upon a position statement for venetoclax-based fixed-duration treatment strategies for Arab patients with CLL.
View Article and Find Full Text PDFInt J Mol Sci
February 2025
Department of Laboratory Medicine, Division of Biomolecular and Cellular Medicine, Karolinska Institutet, 17177 Stockholm, Sweden.
Chronic lymphocytic leukemia (CLL) cells depend on microenvironment niches for proliferation and survival. The adhesion of tumor cells to stromal cells in such niches triggers the activation of signaling pathways crucial for their survival, including B-cell receptor (BCR) signaling. While inhibitors of Bruton's tyrosine kinase (BTKi) have shown efficacy in patients with CLL by disrupting these interactions, acquired resistance and toxicity remain a challenge during long-term therapy.
View Article and Find Full Text PDFDiagnostics (Basel)
March 2025
Department of Pathology, Microbiology and Immunology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Fluorescence in situ hybridization (FISH) testing against chromosome 12 centromere (CEN12) is routinely included in the work-up of patients with suspected chronic lymphocytic leukemia (CLL) or monoclonal B-cell lymphocytosis (MBL). However, incidental findings can occur and be challenging. : Interphase and metaphase FISH analyses with various probes, including CEN12 probes from different vendors, and conventional cytogenetics were applied.
View Article and Find Full Text PDFCancers (Basel)
March 2025
Division of Hematology, Department of Translational Medicine, Università del Piemonte Orientale and Azienda Ospedaliero-Universitaria Maggiore della Carità, 28100 Novara, Italy.
Histological transformation (HT) into aggressive lymphoma is a turning point in a significant fraction of patients affected by indolent lymphoproliferative neoplasms, namely, chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), marginal zone lymphomas (MZLs), and lymphoplasmacytic lymphoma (LPL) [...
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