Publications by authors named "Civallero M"

Article Synopsis
  • Variations in access to drugs globally make it hard to assess the effectiveness of modern treatments for patients with relapsed and refractory mature T-cell and NK-cell lymphomas in a study of 925 patients.
  • * The study found that relapsed lymphoma patients had better overall survival rates compared to refractory patients after second-line treatment, with several factors identified as predictors of survival.
  • * A new prognostic index (PIRT) categorizes patients based on risk factors into low, intermediate, or high risk, impacting 3-year overall survival rates, and highlights the superior outcomes of novel therapies compared to traditional chemotherapy.
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Introduction: The histological transformation (HT) of follicular lymphoma (FL) is a crucial biological event. The study aimed to evaluate the incidence, clinicial characteristics, prognosis and impact of HT time on survival of FL transforming to diffuse large B-cell lymphoma in population-based large-scale cohorts.

Methods: A retrospective cohort study of FL with HT was performed in the Surveillance, Epidemiology, and End Results database.

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Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of haematological cancers with generally poor clinical outcomes. However, a subset of patients experience durable disease control, and little is known regarding long-term outcomes. The International T-cell Lymphoma Project (ITCLP) is the largest prospectively collected cohort of patients with PTCLs, providing insight into clinical outcomes at academic medical centres globally.

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We report the outcome of 563 cases of newly diagnosed lymphoma registered in 2019-2021, including 176 cases (31.2%) of Hodgkin lymphoma (HL), 130 (23.1%) of diffuse large B-cell lymphoma (DLBCL), 28 (5%) of follicular lymphoma (FL), 16 (2.

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Article Synopsis
  • The study examined outcomes and prognostic factors in patients with limited-stage peripheral T-cell lymphomas (PTCLs) using data from the T-Cell Project, involving 211 patients from 2006-2018.
  • A newly developed model identified risk groups based on factors like age, LDH levels, and serum albumin, showing varying 5-year overall survival rates (OS) of 78%, 46%, and 25% for low, intermediate, and high-risk groups, respectively.
  • The SALENTO Model outperformed existing prognostic indices and revealed that high-risk patients have poor outcomes similar to advanced-stage disease, suggesting a need for more aggressive first-line treatments.
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Introduction: Triple-negative breast cancer (TNBC) patients who do not obtain pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) present higher rate of relapse and worse overall survival. Risk factors for relapse in this subset of patients are poorly characterized. This study aimed to identify the predictive factors for relapse in TNBC patients without pCR after NACT.

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Article Synopsis
  • The T-cell Lymphoma Project is a global study that examined clinical features and treatment outcomes of patients with newly diagnosed peripheral T-cell and NK-cell lymphomas, enrolling 1553 patients from 74 institutions across 14 countries between 2006 and 2018.
  • Among the participants, 131 (8.4%) were identified with anaplastic large cell lymphoma - kinase positive (ALCL, ALK+), mostly in young adults with a median age of 39; many patients had advanced-stage disease but a majority had low-risk scores.
  • Treatment with anthracycline chemotherapy yielded an 81% overall response rate, with 70% achieving complete remission, and three- and five-year overall survival rates
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  • Angioimmunoblastic T-cell lymphoma (AITL) is a serious subtype of peripheral T-cell lymphoma with distinct characteristics and a generally poor prognosis, affecting mostly older patients with advanced disease.
  • A study analyzed data from 282 AITL patients over 12 years, finding a 5-year overall survival rate of 44% and a progression-free survival rate of 32%, with improved outcomes for those who received stem cell transplants.
  • Key factors influencing survival included age, performance status, and specific lab markers, leading to the development of a new prognostic score that better distinguishes risk levels and highlights the need for more effective treatments.
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Previous research involving epithelial ovarian cancer patients showed that, compared to germline (gBRCA) mutations, somatic (sBRCA) mutations present a similar positive impact with regard to overall survival (OS) and platinum and PARP (poly (ADP-ribose) polymerase) inhibitor sensitivity. Nevertheless, molecular testing in these studies did not include copy number variation (CNV) analyses of genes. The aim of this study was to explore the prognostic and predictive role of sBRCA mutations as compared to gBRCA mutations in patients who were also tested for CNVs.

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  • Anaplastic lymphoma kinase-negative anaplastic large cell lymphoma (ALK- ALCL) is a type of aggressive cancer affecting T-cells, with a median diagnosis age of 54 and a majority of male patients (62%).
  • Out of 1,553 cases studied globally, 71% were at advanced stages (III-IV), and 85% received multiagent chemotherapy, showing initial response rates of 77% overall and 63% complete.
  • After a median follow-up of 52 months, progression-free survival was 41 months, and overall survival was 55 months, with treatments including anthracycline and etoposide yielding better overall survival outcomes.
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Article Synopsis
  • HDAC inhibitors, like citarinostat, are promising antitumor drugs with low toxicity to normal cells, while momelotinib specifically targets a key signaling pathway in certain blood disorders like myelofibrosis.
  • Researchers hypothesized that combining HDAC and JAK/STAT pathway inhibitors would enhance treatment effectiveness for lymphoproliferative disorders without increasing toxicity.
  • The combination of citarinostat and momelotinib showed strong cytotoxic effects in lymphoid cell lines, involving reduced mitochondrial function and activation of cell death pathways, suggesting a potential new strategy for cancer treatment.
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  • Extranodal natural killer (NK) T-cell lymphoma (ENKTL) is a rare cancer associated with poor survival rates, predominantly studied in East Asian populations, leaving a gap in international data on treatment outcomes.
  • This research is part of the T-cell Project, which tracked newly diagnosed NK and T-cell lymphoma patients from 13 countries, enrolling 1,695 participants and focusing on patient characteristics and survival rates over time.
  • The study found that 5-year overall survival rates were 54% for patients with nasal ENKTL and 34% for those with extranasal disease, representing the largest global dataset on ENKTL and highlighting significant improvements in patient survival with routine treatment practices.
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The T Cell Project was the largest prospective trial to explore the incidence, treatment patterns, and outcomes for T cell lymphomas. The rare subtypes of T cell lymphomas, including hepatosplenic T cell lymphoma (HSTCL), enteropathy associated T cell lymphoma (EATL), and peripheral gamma delta T cell lymphomas (PGDTCLs) are poorly represented in most studies and there is little data regarding treatment patterns. We report results from 115 patients with hepatosplenic (n = 31), enteropathy associated (n = 65), and PGDTCLs (n = 19).

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Owing to their nano-sized porous structure, CaCO₃ nanocrystals (CaCO₃NCs) hold the promise to be utilized as desired materials for encapsulating molecules which demonstrate wide promise in drug delivery. We evaluate the possibility to encapsulate and release NVP-BEZ235, a novel and potent dual PI3K/mTOR inhibitor that is currently in phase I/II clinical trials for advanced solid tumors, from the CaCO₃NCs. Its chemical nature shows some intrinsic limitations which induce to administer high doses leading to toxicity; to overcome these problems, here we proposed a strategy to enhance its intracellular penetration and its biological activity.

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JAK-2 dysregulation plays an important role as an oncogenic driver, and is thus a promising therapeutic target in hematological malignancies. Ruxolitinib is a pyrrolo[2.3-d]pyrimidine derivative with inhibitory activity against JAK1 and JAK2, moderate activity against TYK2, and minor activity against JAK3.

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Histone deacetylase inhibitors (HDACis) have emerged as a new class of anticancer agents, targeting the biological process including cell cycle and apoptosis. We investigated and explained the anticancer effects of an HDAC6 inhibitor, ricolinostat alone and in combination with bendamustine in lymphoma cell lines. Cell viability was measured by MTT assay.

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We investigated the cytotoxic interactions of romidepsin, a histone deacetylase inhibitor, and lenalidomide, an immunomodulatory agent, in a T-cell lymphoma preclinical model. Hut-78 and Karpas-299 cells were treated with romidepsin and lenalidomide alone and in combination. The interaction between romidepsin and lenalidomide was evaluated by the Chou-Talalay method, and cell viability and clonogenicity were also evaluated.

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Non-Hodgkin lymphomas encompass a heterogeneous group of cancers, with 85-90% arising from B lymphocytes and the remainder deriving from T lymphocytes or NK lymphocytes. These tumors are molecularly and clinically heterogeneous, showing dramatically different responses and outcomes with standard therapies. Deregulated PI3K signaling is linked to oncogenesis and disease progression in hematologic malignancies and in a variety of solid tumors and apparently enhances resistance to antineoplastic therapy, resulting in a poor prognosis.

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We analyzed the combination of a proteasome inhibitor (bortezomib) with enzastaurin (PKC/AKT-inhibitor) or lenalidomide (immunomodulatory agent) for the inhibition of proliferation and induction of apoptosis in B-cell lymphoma cell lines and primary malignant cells. The effects of bortezomib, enzastaurin or lenalidomide, alone or in combinations, on cell viability and apoptosis were evaluated using the Cell Proliferation Kit and flow cytometry analysis. The interaction between drugs was examined by the Chou-Talalay method.

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Objectives: Mantle cell lymphoma (MCL) is a distinct subtype of B-cell lymphoma; the complete response rate for standard therapies in use today is 85 - 90%. NVP-BEZ235 inhibits the PI3K/Akt/mTOR signaling axis at the level of both PI3K and mTOR. In this study, we analyzed the inhibitory effects of NVP-BEZ235 on mantle cell lines and its effects in combination with enzastaurin, everolimus and perifosine.

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Less toxic and more active treatments are needed for indolent lymphomas as there is no curative treatment, and patients eventually die due to complications related to their disease. The purpose of the present study was to assess the antitumour activity of the combination of low doses of Enzastaurin and Lenalidomide (Revlimid) on B-lymphoma cell lines. The combination of Enzastaurin and Lenalidomide, at doses as low as 1 μM, showed strong synergism against indolent lymphomas by reducing cell growth, producing an increase in G0-G1 phase followed by significant decrease in S phase, increasing apoptosis, and inhibiting PI3K/AKT, PKC and MAPK/ERK pathways.

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