Real-world efficacy and safety of fostamatinib in ITP patients: Italian multicentre experience. GIMEMA ITP1122 study.

The efficacy and safety of fostamatinib in adult patients with persistent/chronic immune thrombocytopenia (p/c ITP) were demonstrated in the FIT-1/FIT-2 trials. This retrospective, multicentre observational study evaluated real-world outcomes in consecutive p/c ITP patients treated with fostamatinib in Italy. The primary end-point, serving as a surrogate for both efficacy and safety, was the proportion of patients receiving fostamatinib for at least 6 months.

Integration of [F]FDG-PET radiomics with liquid biopsy improves outcome prediction in newly diagnosed diffuse large B-cell lymphoma.

Early identification of relapsing/refractory diffuse large B-cell lymphoma (DLBCL) represents an unmet clinical need. A real-life cohort of newly diagnosed DLBCL (n = 120) treated with R-CHOP was investigated. Using the standardized uptake value (SUV) threshold of 4.

Disease-specific U1 spliceosomal RNA mutations in mature B-cell neoplasms.

Recurrent mutations in the third base of U1 spliceosomal RNA responsible for marked splicing and expression abnormalities have been described in chronic lymphocytic leukemia (CLL) and some solid tumors. However, the clinical significance of these mutations in large and independent CLL cohorts as well as their presence in other B-cell neoplasms is unknown. Here we characterized U1 mutations in 1670 CLL and 363 mature B-cell lymphomas.

Innovative Use of Fostamatinib in Managing Refractory Immune Thrombocytopenia in an HIV-Positive Patient: A Case Report.

Managing immune thrombocytopenia (ITP) in HIV patients remains challenging due to refractory cases and treatment limitations. This report highlights fostamatinib as a safe, effective, and antiretroviral therapy-compatible option, offering durable platelet stabilization in a difficult-to-treat population.

Richter transformation in diffuse large B-cell lymphoma in patients with chronic lymphocytic leukemia receiving ibrutinib: risk factors and outcomes.

This study aimed to define the incidence and risk factors for diffuse large B cell lymphoma variant of RT (DLBCL-RT) in 976 patients with CLL who received ibrutinib therapy. DLBCL-RT was recorded in 83 (8.5%) patients, with a 7-year 15.

Resistance to targeted therapies in chronic lymphocytic leukemia: Current status and perspectives for clinical and diagnostic practice.

The integration of BTK and BCL2 inhibitors into the treatment of patients with chronic lymphocytic leukemia (CLL) represents a paradigm shift and has led to significant improvements in clinical outcomes, including prolonged survival and enhanced quality of life. However, despite the efficacy of these agents, resistance to targeted therapy remains a major challenge, ultimately resulting in treatment failure and disease progression for a significant proportion of patients. Related to this, diagnostic testing for genetic variants associated with resistance, such as mutations in BTK, PLCG2 and BCL2, may become an increasingly common part of clinical routine practice.

Primary Extranodal Follicular Lymphoma: A Retrospective Survey of the International Extranodal Lymphoma Study Group (IELSG).

The characteristics at diagnosis and clinical course of primary extranodal follicular lymphoma (EFL) have not been extensively described. The International Extranodal Lymphoma Study Group (IELSG) conducted an international retrospective survey aimed to describe the clinical features at diagnosis and the outcomes of FL cases with a clinically dominant extranodal component. The dataset included 605 pathologically reviewed cases from 19 different countries, and their outcomes were compared to those of nodal follicular lymphomas.

Assessing frailty in patients with relapsed/refractory multiple myeloma: A comparison between the patient-reported frailty phenotype and the International Myeloma Working Group frailty index.

Introduction: The International Myeloma Working Group Frailty Index (IMWG FI) is one of the most used frailty assessment tools in patients with multiple myeloma (MM). A patient-centered frailty tool based on patient-reported outcomes (PROs) has been recently proposed for patients with relapsed/refractory MM (RRMM): the Patient-Reported Frailty Phenotype (PRFP). This cross-sectional analysis aimed to replicate the PRFP within a real-world setting and to describe health-related quality of life (HRQoL) profiles based on this new patient-centered frailty classification.

Liquid Biopsy in B and T Cell Lymphomas: From Bench to Bedside.

Liquid biopsy through the analysis of circulating tumor DNA (ctDNA) is emerging as a powerful and non-invasive tool complementing tissue biopsy in lymphoma management. Whilst tissue biopsy remains the diagnostic gold standard, it fails to detect the molecular heterogeneity of the tumor's multiple compartments and poses challenges for sequential disease monitoring. In diffuse large-B-cell lymphoma (DLBCL), ctDNA facilitates non-invasive genotyping by identifying hallmark mutations (e.

A comprehensive genetic study of classic Hodgkin lymphoma using circulating tumor DNA.

This study analyzed the genetics of classic Hodgkin lymphoma (cHL) by using circulating tumor DNA (ctDNA). Two genetic subtypes were identified, differing in genetic instability mechanisms: one subtype (64% of cases) showed a higher mutation load and a higher fraction of mutations associated with activation-induced cytidine deaminase and microsatellite instability signatures, whereas the other subtype (36% of cases) exhibited chromosomal instability with more somatic copy number alterations. Whole-genome duplication was more common in cHL compared with other B-cell tumors and emerged as a prognostic biomarker for patients undergoing Adriamycin (doxorubicin)-bleomycin-vinblastine-dacarbazine-based therapy.

ATM aberrations in chronic lymphocytic leukemia: del(11q) rather than ATM mutations is an adverse-prognostic biomarker.

Despite the well-established adverse impact of del(11q) in chronic lymphocytic leukemia (CLL), the prognostic significance of somatic ATM mutations remains uncertain. We evaluated the effects of ATM aberrations (del(11q) and/or ATM mutations) on time-to-first-treatment (TTFT) in 3631 untreated patients with CLL, in the context of IGHV gene mutational status and mutations in nine CLL-related genes. ATM mutations were present in 246 cases (6.

International consensus statement on diagnosis, evaluation, and research of Richter transformation: the ERIC recommendations.

Richter transformation (RT) is defined as an aggressive lymphoma emerging in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL). Despite novel therapeutics developed in CLL, RT is associated with poor outcomes. In light of recent progress regarding the diagnostic procedures and therapeutic concepts of RT, an international group of experts, under the coordination of the European Research Initiative on CLL, has developed consensus recommendations for clinical procedures and future research on this disease.

Comparative Analysis of the Performance of Automated Digital Cell Morphology Analyzers for Leukocyte Differentiation in Hematologic Malignancies: Mindray MC-80 Versus West Medical Vision Hema.

Introduction: The use of artificial intelligence in hematology laboratories has improved the diagnostic evaluation of peripheral blood cells. The aim of this study is to compare the performance of two automated digital cell morphology analyzers, the Mindray MC-80 and the West Medical Vision Hema Pro, with manual microscopy, the gold standard, for leukocyte differentiation in patients with hematologic malignancies and infections.

Methods: Peripheral blood smears from 75 patients were analyzed, including cases of acute lymphoblastic leukemia (ALL, 4), chronic lymphocytic leukemia (CLL, 20), acute myeloid leukemia (AML, 20), chronic myeloid leukemia (CML, 5), other lymphoproliferative disorders (LPD, 20), and infections (6).

Molecular Mechanisms in the Transformation from Indolent to Aggressive B Cell Malignancies.

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) [...

Molecular clustering on ctDNA improves the prognostic stratification of patients with DLBCL compared with ctDNA levels.

Circulating tumor DNA (ctDNA) levels can help predict outcomes in diffuse large B-cell lymphoma (DLBCL), but its integration with DLBCL molecular clusters remains unexplored. Using the LymphGen tool in 77 DLBCL cases with both ctDNA and tissue biopsy, a 95.8% concordance rate in molecular cluster assignment was observed, showing the reproducibility of molecular clustering on ctDNA.

Venetoclax therapy in chronic lymphocytic leukaemia patients relapsed after allogeneic haematopoietic stem cell transplantation.

Allogeneic hematopoietic stem cell transplantation (alloHSCT) remains an option for young and fit chronic lymphocytic leukaemia (CLL) patients with high-risk disease features. However, allotransplanted patients are generally excluded from clinical trials, making data regarding the use of venetoclax after alloHSCT extremely rare. We report data from 7 CLL patients who received venetoclax after alloHSCT among 53 Italian centers.

Molecular measurable residual disease by immunoglobulin gene rearrangements on circulating tumor DNA predicts outcome in diffuse large B-cell lymphoma.

In diffuse large B-cell lymphoma (DLBCL) treatment response relies on imaging. We investigated the potential value of molecular measurable residual disease (MRD) on circulating tumor DNA (ctDNA) to predict the outcome of 73 DLBCL patients. At baseline, next-generation sequencing was used to detect clonal immunoglobulin (IG) gene rearrangements on tumor biopsies (N=57) and ctDNA (N=73).

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.

Efficacy and safety of bendamustine, rituximab and bortezomib treatment in relapsed/refractory Waldenstrom Macroglobulinaemia: results of phase 2 single-arm FIL-BRB trial.

This multicentre phase II study Fondazione Italiana Linfomi (FIL)-bortezomib plus rituximab plus bendamustine (BRB) tested a combination of bendamustine (90 mg/m on days 1-2), rituximab (375 mg/m intravenously on day 1) and bortezomib (1.3 mg/m sc on days 1, 8, 15, 22) every 28 days for six cycles in 38 symptomatic patients with relapsed/refractory Waldenstrom macroglobulinaemia (RR-WM). Moreover, MYD88 and CXCR4 mutations were tested by droplet digital polymerase chain reaction (ddPCR) both at baseline and at the end of treatment in 21 patients.

CAT rs1001179 Single Nucleotide Polymorphism Identifies an Aggressive Clinical Behavior in Chronic Lymphocytic Leukemia.

Chronic lymphocytic leukemia (CLL) is characterized by an extremely variable clinical course. Although several parameters have been shown to be associated with clinical outcomes in patients with CLL, there remains substantial intragroup clinical heterogeneity in otherwise molecularly and staging homogeneous CLL subgroups. We have recently shown that high catalase (CAT) expression identifies patients with an aggressive clinical course and that higher CAT expression is associated with the presence of the rs1001179 single nucleotide polymorphism (SNP) T allele in the CAT promoter.

High Mitophagy and Low Glycolysis Predict Better Clinical Outcomes in Acute Myeloid Leukemias.

Acute myeloid leukemia (AML) emerges as one of the most common and fatal leukemias. Treatment of the disease remains highly challenging owing to profound metabolic rewiring mechanisms that confer plasticity to AML cells, ultimately resulting in therapy resistance. Autophagy, a highly conserved lysosomal-driven catabolic process devoted to macromolecular turnover, displays a dichotomous role in AML by suppressing or promoting disease development and progression.

A Rare Case of Life-Threatening Jaundice Caused by Epstein-Barr Virus Infection and Secondary Cold Agglutinin Syndrome Successfully Treated with Rituximab.

Background: Jaundice and hyperbilirubinemia are common clinical problems characterized by the presence of bile pigments in the blood and their deposition in body tissues. This clinical condition can be associated with a broad spectrum of potential benign and malignant causes, including hepatic inflammation, biliary obstruction, impaired bilirubin conjugation and bilirubin overproduction Therefore, the hyperbilirubinemia diagnostic work-up sometimes can be highly challenging and its therapeutic management can require a multidisciplinary approach.

Case Report: We report on a unique case of life-threatening jaundice and hepatic failure in a 20-year-old female who presented to the emergency room with complaints of fever, constant left abdominal pain and generalized profuse fatigue.