Predictors of Splenectomy Response in Immune Thrombocytopenia: A Multicentric Italian Study.

: Splenectomy leads to a high rate of remission in chronic primary immune thrombocytopenia (ITP), but its unpredictable long-term positive outcomes and that it is a irreversible surgical approach discourage clinicians and patients. The identification of predictors of response may redefine the timing of splenectomy. In this retrospective, multicentric study we aimed to investigate clinical-histological predictors of splenectomy response in ITP patients and provide an easy-to-use score to predict splenectomy response in ITP.

Outcomes and prognostic indicators in daratumumab-refractory multiple myeloma: a multicenter real-world study of elotuzumab, pomalidomide, and dexamethasone in 247 patients.

Background: Daratumumab-refractory multiple myeloma (Dara-R MM) presents a significant treatment challenge. This study aimed to evaluate the efficacy and survival outcomes of elotuzumab, pomalidomide, and dexamethasone (EloPd) in a large, real-world cohort of patients with Dara-R MM, with particular focus on progression-free survival (PFS) and overall survival (OS).

Materials And Methods: This retrospective analysis included 247 Dara-R MM patients treated with EloPd.

Proteasome Inhibitors Induce Apoptosis in Ex Vivo Cells of T-Cell Prolymphocytic Leukemia.

Finding an effective treatment for T-PLL patients remains a significant challenge. Alemtuzumab, currently the gold standard, is insufficient in managing the aggressiveness of the disease in the long term. Consequently, numerous efforts are underway to address this unmet clinical need.

T-cell clones of uncertain significance. When is the rogue clone dangerous?

T-cell large granular lymphocyte clones that persist over time and that exhibit molecular and immunophenotypic features closely resembling those of T-cell large granular lymphocyte leukemia (T-LGLL) may be detectable in individuals who lack any clinical or laboratory features supporting a diagnosis of a T-cell malignancy. This condition represents a potential precursor state termed T-cell clones of uncertain significance (T-CUS). T-CUS represents the even more benign extreme of the wide spectrum of clonal T-large granular lymphocyte proliferations, emphasizing the need for an appropriate multiparametric diagnostic assessment that avoids misdiagnosis of T-cell neoplasia.

Belantamab mafodotin in triple-refractory multiple myeloma patients: A retro-prospective observational study in Italy.

Belantamab mafodotin is the first-in-class antibody-drug conjugates targeting B-cell maturation antigen to have demonstrated effectiveness in triple-class refractory multiple myeloma (TCR-MM) patients. We performed a retrospective study including 78 TCR patients, with at least four prior lines of therapy (LOTs), who received belantamab mafodotin within named patient program and expanded access program in Italy between 2020 and 2022. Median age was 65 years (range 42-86 years), ECOG performance status was ≥1 in 45% of patients.

When Waldenström macroglobulinemia hits the kidney: Description of a case series and management of a "rare in rare" scenario.

Background: Renal injury related to Waldenström macroglobulinemia (WM) occurs in approximately 3% of patients. Kidney biopsy is crucial to discriminate between distinct histopathological entities such as glomerular (amyloidotic and non-amyloidotic), tubulo-interstitial and non-paraprotein mediated renal damage. In this context, disease characterization, management, relationship between renal, and hematological response have been poorly explored.

A real-world retrospective-prospective analysis of efficacy and safety of combined ixazomib, lenalidomide, and dexamethasone in relapsed/refractory multiple myeloma: The northern Italy experience.

Introduction: Ixazomib, lenalidomide, and dexamethasone (IRd) have been approved for the treatment of relapsed/refractory multiple myeloma (RRMM) based on the results of the TOURMALINE-MM1.

Objectives And Methods: We conducted a retrospective-prospective analysis of 106 RRMM patients (pts) treated with IRd in 21 centers in Northern Italy, with the aim to evaluate the efficacy and safety of IRd in real life.

Results: At IRd initiation, 34% of pts were aged ≥75 (median 72.

The constitutive activation of STAT3 gene and its mutations are at the crossroad between LGL leukemia and autoimmune disorders.

Type T Large Granular Lymphocyte Leukemia (T-LGLL) is a chronic disorder characterized by the abnormal proliferation of clonal cytotoxic T cells. The intriguing association of T-LGLL with autoimmune and inflammatory diseases, the most prominent example being rheumatoid arthritis, raises questions about the underlying pathophysiologic relationships between these disorders which share several biological and clinical features, most notably neutropenia, which is considered as a clinical hallmark. Recent progress in molecular genetics has contributed to a better understanding of pathogenetic mechanisms, thus moving our knowledge in the field of LGL leukemias forward.

Predictors of unsustained measurable residual disease negativity in patients with multiple myeloma.

The prognostic impact of achieving and in particular maintaining measurable residual disease (MRD) negativity in multiple myeloma is now established; therefore, identifying among MRD-negative patients the ones at higher risk of losing MRD negativity is of importance. We analyzed predictors of unsustained MRD negativity in patients enrolled in the FORTE trial (NCT02203643). MRD was performed by multiparameter flow cytometry (sensitivity of 10-5) at premaintenance and every 6 months thereafter.

Pro-inflammatory cells sustain leukemic clonal expansion in T-cell large granular lymphocyte leukemia.

T-cell large granular lymphocyte leukemia (T-LGLL) is a chronic lymphoproliferative disorder characterized by the clonal expansion of T-cell large granular lymphocytes (T-LGL). Immunophenotypic and genotypic features contribute to discriminate symptomatic (CD8+ STAT3-mutated T-LGLL) from clinically indolent patients, this latter group including CD8+ wildtype (wt), CD4+ STAT5B-mutated and wt cases. T-LGL lymphoproliferation is sustained both by somatic gain-offunction mutations (i.

Tixagevimab/Cilgavimab as pre-exposure prophylaxis against SARS-CoV-2 in patients with hematological malignancies.

The 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.

Impact of minimal residual disease standardised assessment by FDG-PET/CT in transplant-eligible patients with newly diagnosed multiple myeloma enrolled in the imaging sub-study of the FORTE trial.

Background: 18F-FDG-PET/CT is the current standard technique to define minimal residual disease (MRD) outside the bone marrow (BM) in multiple myeloma (MM), recently standardised applying the Deauville scores (DS) to focal lesions (FS) and bone marrow uptake (BMS) and defining the complete metabolic response (CMR) as uptake below the liver background (DS <4).

Methods: In this analysis, we aimed at confirming the role of CMR, and complementarity with BM multiparameter flow cytometry (MFC) at 10, in an independent cohort of newly diagnosed transplant-eligible MM patients previously enrolled in the phase II randomised FORTE trial. 109 of the 474 global patients enrolled in the trial between February 23, 2015, and April 5, 2017, who had paired PET/CT (performed at baseline [B] and preceding maintenance therapy [PM]) and MFC evaluation, were included in this analysis.

Long-term follow-up of rituximab plus bendamustine and cytarabine in older patients with newly diagnosed MCL.

The combination of rituximab, bendamustine, and low-dose cytarabine (R-BAC) has been studied in a phase 2 prospective multicenter study from Fondazione Italiana Linfomi (RBAC500). In 57 previously untreated elderly patients with mantle cell lymphoma (MCL), R-BAC was associated with a complete remission rate of 91% and 2-year progression-free survival (PFS) of 81% (95% confidence interval [CI], 68-89). Here, we report the long-term survival outcomes, late toxicities, and results of minimal residual disease (MRD) evaluation.

Not all LGL leukemias are created equal.

Large Granular Lymphocyte (LGL) Leukemia is a rare, heterogeneous even more that once thought, chronic lymphoproliferative disorder characterized by the clonal expansion of T- or NK-LGLs that requires appropriate immunophenotypic and molecular characterization. As in many other hematological conditions, genomic features are taking research efforts one step further and are also becoming instrumental in refining discrete subsets of LGL disorders. In particular, STAT3 and STAT5B mutations may be harbored in leukemic cells and their presence has been linked to diagnosis of LGL disorders.

Real-world use of carfilzomib combined with lenalidomide and dexamethasone in patients with multiple myeloma in Europe and Israel.

Clinical trials have demonstrated the efficacy and safety of carfilzomib in patients with relapsed/refractory multiple myeloma (RRMM); however, prospective real-world data are limited. This real-world, prospective, observational study evaluated carfilzomib use, effectiveness and safety in adults with RRMM. Data are presented for a subset of patients ( = 383) who received carfilzomib in combination with lenalidomide and dexamethasone (KRd).

Experts' consensus on the definition and management of high risk multiple myeloma.

High risk multiple myeloma (HRMM) at diagnosis is currently recognized according to the Revised International Staging System (R-ISS) which was set up in 2015. Since then, new clinical and biological prognostic factors have been developed, which could implement the definition of High Risk (HR) category. We conducted a survey in order to identify which additional parameters, both clinical and biological, are considered more useful for the clinical practice and to evaluate if the management of Multiple Myeloma (MM) should change on the basis of the risk category.

Real-World Use and Effectiveness of Carfilzomib Plus Dexamethasone in Relapsed/Refractory Multiple Myeloma in Europe.

This prospective, observational study examined the real-world use of carfilzomib across 11 European countries in adults with relapsed/refractory multiple myeloma (RRMM) who received at least one prior line of therapy. Carfilzomib and dexamethasone (Kd) use, effectiveness and safety were analyzed. In total, 271 patients received Kd among 701 adults enrolled.

LGL Clonal Expansion and Unexplained Cytopenia: Two Clues Don't Make an Evidence.

Clonal expansions of large granular lymphocytes (LGL) have been reported in a wide spectrum of conditions, with LGL leukemia (LGLL) being the most extreme. However, the boundaries between LGLL and LGL clones are often subtle, and both conditions can be detected in several clinical scenarios, particularly in patients with cytopenias. The intricate overlap of LGL clonal expansion with other disease entities characterized by unexplained cytopenias makes their classification challenging.

A bone-based 3D scaffold as an model of microenvironment-DLBCL lymphoma cell interaction.

About 30% of patients with diffuse large B-cell lymphoma (DLBCL) relapse or exhibit refractory disease (r/r DLBCL) after first-line immunochemotherapy. Bone marrow (BM) involvement confers a dismal prognosis at diagnosis, likely due to the interaction between neoplastic cells and a complex tumor microenvironment (TME). Therefore, we developed a 3D model from human decellularized femoral bone fragments aiming to study the role of mesenchymal stromal cells (MSC) and the extracellular matrix (ECM) in the adaptation, growth, and drug resistance of DLBCL lymphoma cells.