Leukaemic cells from hairy cell leukaemia (HCL) secrete a soluble form of the interleukin-2 receptor (sIL-2R) which is measurable in serum. Previous evidence suggested that sIL-2R may correlate well with tumour burden and demonstrated a reduction in sIL-2R levels after therapy with recombinant interferon-α2. We evaluated the role of sIL-2R as a new prognostic factor and as a tool for disease monitoring.
View Article and Find Full Text PDFUnlabelled: In Chronic Lymphocytic Leukemia (CLL), t(14;19)(q32;q13), leading to the overexpression of BCL3, is found in ∼1% of cases and is associated with an aggressive disease. In this study, leveraging a large CLL patient cohort collected thanks to an international collaboration, we investigate for the first time the circular transcriptome (circRNAome) associated with the rare t(14;19), in comparison with CLL without t(14;19) and B cells of age-matched healthy donors. We described the circRNAs commonly dysregulated in CLL, including circCSNK1G3 and circEXOC6B(3–5), which were depleted, and circZNF609 and circLPAR3, which were overexpressed in malignant cells.
View Article and Find Full Text PDFIntroduction: Chronic Lymphocytic Leukemia (CLL) is a disease marked by high infectious risk due to a combination of patient, disease and treatment-related factors. As a new landscape in the therapeutic panorama is emerging with the introduction of novel agents, it is essential to understand their impact on the incidence of infectious events and consequently what prevention and management strategies should be introduced.
Areas Covered: We searched the PUBMED database considering peer-reviewed papers published between January 2013 and January 2025 that reported on at least 100 patients and provided detailed information on infectious complications.
Familial chronic lymphocytic leukemia (CLL) constitutes 5-7% of CLL and has previously shown a more aggressive pattern of evolution compared to sporadic CLL, even if no difference in overall survival (OS) has been observed. This multicenter case-control study aimed to compare clinical features, molecular biomarkers, and patient outcomes of familial and sporadic CLL. Adult CLL patients were enrolled from 18 Italian centers, with familial CLL defined as having at least one first-degree relative affected by CLL.
View Article and Find Full Text PDFOctogenarians represent a significant fraction of patients with chronic lymphocytic leukemia (CLL) but, despite the prevalence of the disease in this age group, limited data are available on the safety and efficacy of novel drugs in this subgroup. We conducted a multicenter retrospective study enrolling 120 octogenarian patients who received venetoclax (Ven) regimens in any line. Regarding efficacy, we found Ven to perform similarly to what is reported in younger patients with CLL, with an overall response rate of 91%, a complete response rate of 44%, and median progression-free survival of 44 months.
View Article and Find Full Text PDFChronic lymphocytic leukaemia (CLL) is a heterogeneous disease characterised by the uncontrolled proliferation of mature lymphocytes. A subset of CLL patients harbouring complex karyotype (CK) presents with poor prognosis and limited treatment options. This review aims to discuss the current understanding of such patient subset, including its molecular landscape, diagnostic approaches, treatment modalities and emerging therapies.
View Article and Find Full Text PDFIntroduction: The identification of baseline prognostic factors in Classical Hodgkin Lymphoma could help in tailoring a risk-based approach as the therapeutic landscape expands. Currently, the International Prognostic Score (IPS) represents the most used prediction tool in clinical practice, but other potential baseline risk predictors have been identified.
Methods: We performed a retrospective analysis in a cohort of 274 patients treated with FDG-PET/CT-guided ABVD to assess the prognostic significance of the IPS risk factors, and to validate the impact of the peripheral blood lymphocyte to monocyte (LMR) and neutrophil to lymphocyte (NLR) ratios on prognosis definition.
Introduction: In classical Hodgkin lymphoma (cHL), the survival of neoplastic cells is mediated by the activation of NF-κB, JAK/STAT and PI3K/Akt signaling pathways. CK2 is a highly conserved serine/threonine kinase, consisting of two catalytic (α) and two regulatory (β) subunits, which is involved in several cellular processes and both subunits were found overexpressed in solid tumors and hematologic malignancies.
Methods And Results: Biochemical analyses and assays showed an impaired expression of CK2 subunits in cHL, with CK2α being overexpressed and a decreased expression of CK2β compared to normal B lymphocytes.
Although the unfavourable prognostic role of complex karyotype (CK) in chronic lymphocytic leukaemia (CLL) patients treated with chemoimmunotherapy has been clarified, its impact on the outcome of patients being treated with novel targeted agents, and especially with venetoclax-based regimens, remains to be resolved. In fact, only few studies, utilizing data derived from clinical trials (e.g.
View Article and Find Full Text PDFVenetoclax (VEN) has been shown to play a synergistic effect in combination with hypomethylating agents (HMAs) in the frontline treatment of acute myeloid leukemia (AML). However, the potential role of this therapy in the relapsed/refractory (R/R) AML setting, still needs to be further unveiled. The aim of the current study was to retrospectively outline the safety profile, response and survival outcomes of R/R AML patients treated with VEN in association with HMAs.
View Article and Find Full Text PDFChronic lymphocytic leukemia (CLL) exhibits substantial variability in disease course. The mutational status of the B-cell receptor immunoglobulin heavy variable (IGHV) chain is a critical prognostic factor, categorizing patients into mutated (M-IGHV) and unmutated (U-IGHV) groups. Recently, a third subgroup with borderline mutational status (BL-IGHV) has been identified, comprising approximately 5% of CLL cases.
View Article and Find Full Text PDFSignalling events downstream the B-cell receptor (BCR) are central for the survival and progression of chronic lymphocytic leukaemia (CLL) cells. Focal adhesion kinase (FAK), regulated through calpain, interacts with molecules of BCR signalling, cytoskeletal modelling and disease progression, such as Src/Lyn, cortactin and HS1. Hypothesizing that FAK might play a key role in CLL pathogenesis, we observed a down-modulation of FAK whole form, associated with FAK cleavage due to calpain activity upon BCR stimulation.
View Article and Find Full Text PDFThe approved combination of Tixagevimab/Cilgavimab has been shown to decrease the rate of symptomatic SARS-CoV-2 infection in patients at increased risk of inadequate response to vaccination. However, Tixagevimab/Cilgavimab was tested in a few studies that included patients with hematological malignancies, even if this population has shown an increased risk of unfavorable outcomes following infection (with high rates of hospitalization, intensive care unit admission, and mortality) and poor significant immunization following vaccines. We performed a real-life prospective cohort study to evaluate the rate of SARS-CoV-2 infection following pre-exposure prophylaxis with Tixagevimab/Cilgavimab in anti-spike seronegative patients compared to a cohort of seropositive patients who were observed or received a fourth vaccine dose.
View Article and Find Full Text PDFImmune evasion is considered one of the modern hallmarks of cancer and is a key element in the pathogenesis of classical Hodgkin Lymphoma (cHL). This haematological cancer achieves effective avoidance of the host's immune system by overexpressing the PD-L1 and PD-L2 proteins on the surface of the neoplastic cells. Subversion of the PD-1/PD-L axis, however, is not the sole contributor to immune evasion in cHL, as the microenvironment nurtured by the Hodgkin/Reed-Sternberg cells is a major player in the creation of a biological niche that sustains their survival and hinders immune recognition.
View Article and Find Full Text PDFSecondary antibody deficiency (SAD) is a common complication in chronic lymphocytic leukemia (CLL) which favors the development of life-threatening infections. Subcutaneous immunoglobulins (IG) (SCIG) have been proven to be as effective as intravenous immunoglobulin (IVIG) in primary immunodeficiencies. Since only a few studies investigated SCIG in secondary antibody deficiency, the aim of this study was to assess the efficacy and safety of SCIG or IVIG in CLL patients with secondary antibody deficiency.
View Article and Find Full Text PDFFront Oncol
November 2022
One of the main issues in the treatment of patients with chronic lymphocytic leukemia (CLL) deals with the choice between continuous or fixed-duration therapy. Continuous ibrutinib (IB), the first-in-class BTK inhibitor, and obinutuzumab-chlorambucil (G-CHL) are commonly used therapies for elderly and/or comorbid patients. No head-to-head comparison has been carried out.
View Article and Find Full Text PDFThe disease course of chronic lymphocytic leukemia (CLL) is frequently characterized by the occurrence of various complications, such as second primary cancer, which can impact patients' prognoses. While therapies for CLL have evolved tremendously in the past decades, overlooking the possibility of rare neoplasms that arise along with CLL may hinder the benefit that these therapies grant to patients. Moreover, the ability of newer therapies to alter the landscape of these complications is still largely unknown.
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