Publications by authors named "Trneny M"

JCO SEQUOIA (ClinicalTrials.gov identifier: NCT03336333) is a phase III, randomized, open-label trial that compared the oral Bruton tyrosine kinase inhibitor zanubrutinib to bendamustine plus rituximab (BR) in treatment-naïve patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). The initial prespecified analysis (median follow-up, 26.

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Autologous hematopoietic cell transplants (auto-HCTs) remain the standard of care for transplant-eligible MM patients. The general practice has been to undergo upfront apheresis following induction to collect sufficient number of CD34+ cells to facilitate two auto-HCTs. However, 5-30% of MM patients do not initially mobilise a sufficient number of hematopoietic stem cells and are classified as poor mobilizers (PM).

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  • Some patients with a type of cancer called mantle cell lymphoma (MCL) don't have good treatment options if their cancer comes back.
  • A study tested a new medicine called glofitamab, which was given after patients received another medicine to help reduce side effects.
  • The results showed that many patients got better from the treatment, and while some had side effects, these were manageable with proper care.
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Aim: The aim of this study was to analyse the outcomes of patients with large B-cell lymphoma (LBCL) treated with chimeric antigen receptor T-cell therapy (CAR-Tx), with a focus on outcomes after CAR T-cell failure, and to define the risk factors for rapid progression and further treatment.

Methods: We analysed 107 patients with LBCL from the Czech Republic and Slovakia who were treated in ≥3rd-line with tisagenlecleucel or axicabtagene ciloleucel between 2019 and 2022.

Results: The overall response rate (ORR) was 60%, with a 50% complete response (CR) rate.

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The present study was undertaken to provide more information on the peripheral RNA containing ring of ringshaped nucleoli (RSNo). Human lymphocytes of blood donors and patients suffering from B chronic lymphocytic leukemia mostly characterized by RSNo represented very convenient cell models for such study. According to the light microscopy the peripheral RNA ring possessed several highly condensed foci.

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  • The IELSG37 trial investigated whether patients with primary mediastinal B-cell lymphoma (PMBCL) who have a complete metabolic response (CMR) after treatment can safely skip consolidation radiotherapy.
  • It was a randomized noninferiority study involving 545 patients, focusing on progression-free survival (PFS) over 30 months, with results showing high PFS rates of 96.2% for observation and 98.5% for radiotherapy.
  • The study concluded that avoiding irradiation does not negatively impact survival, highlighting positive outcomes for patients with CMR.
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  • Mantle cell lymphoma (MCL) shows recurring genetic changes in key regulators of the phosphoinositol-3-kinase (PI3K) pathway, particularly involving PIK3CA amplifications and PTEN losses.
  • In vitro studies using modified MCL cell lines revealed that PIK3CA overexpression reduces reliance on B-cell receptor (BCR) signaling, alters metabolic processes, and leads to therapy resistance without affecting AKT signaling.
  • Conversely, PTEN knockout resulted in notable changes, including heightened AKT activation, greater resistance to various inhibitors, and decreased reliance on BCR signaling, indicating how these genetic alterations may promote therapy resistance and adaptive survival mechanisms in MCL.
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Autologous(auto-) and allogeneic(allo-) hematopoietic stem cell transplantation (HSCT) are key treatments for relapsed/refractory diffuse large B-cell lymphoma (DLBCL), although their roles are challenged by CAR-T-cells and other immunotherapies. We examined the transplantation trends and outcomes for DLBCL patients undergoing auto-/allo-HSCT between 1990 and 2021 reported to EBMT. Over this period, 41,148 patients underwent auto-HSCT, peaking at 1911 cases in 2016, while allo-HSCT saw a maximum of 294 cases in 2018.

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  • Venetoclax (VEN) shows promising activity against various lymphomas and leukemias, but remissions tend to be short, prompting the need for combination therapies.
  • Research found that combining VEN with A1155463, a BCL-XL inhibitor, created a strong synergistic effect and could overcome resistance in certain cell lines, even those lacking BCL2L11/BIM, which is often linked to VEN resistance.
  • In vivo studies confirmed the effectiveness of this combination in multiple patient-derived models, and a unique treatment schedule of 4 days on/3 days off minimized side effects, making this a potential innovative approach for treating BCL2+ hematologic malignancies.
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Background: Adding ibrutinib to standard immunochemotherapy might improve outcomes and challenge autologous stem-cell transplantation (ASCT) in younger (aged 65 years or younger) mantle cell lymphoma patients. This trial aimed to investigate whether the addition of ibrutinib results in a superior clinical outcome compared with the pre-trial immunochemotherapy standard with ASCT or an ibrutinib-containing treatment without ASCT. We also investigated whether standard treatment with ASCT is superior to a treatment adding ibrutinib but without ASCT.

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  • - This study compared the effectiveness of autologous haematopoietic stem cell transplantation (AHSCT) and natalizumab in patients with progressive multiple sclerosis (MS), highlighting that AHSCT did not significantly improve disability compared to natalizumab.
  • - Researchers matched 39 patients treated with AHSCT to 65 patients on natalizumab and found no significant differences in confirmed disability worsening or improvement over a period of up to 4 years.
  • - Although AHSCT had some complications like febrile neutropenia and serum sickness, there were no treatment-related deaths, but the results suggest AHSCT is not effective for controlling disability in progressive MS patients with advanced disability and low relapse activity. *
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  • Mantle cell lymphoma (MCL) is a cancer characterized by uncontrolled cell growth, and researchers studied how well palbociclib, a CDK 4/6 inhibitor, works alone and with venetoclax, a BCL2 inhibitor, on MCL cells.
  • They conducted experiments using both MCL cell lines and patient-derived models to evaluate the effectiveness, mechanisms, and potential markers that could indicate which patients might benefit from this combination therapy.
  • The findings showed that the combination treatment was more effective than either drug alone, particularly for patients with MCL that does not have RB1 deletion, suggesting a promising approach to treating this type of lymphoma without traditional chemotherapy.
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Immune thrombocytopenia (ITP) is an autoimmune disease associated with autoantibody-mediated platelet destruction and impaired platelet production, resulting in thrombocytopenia and a predisposition to bleeding. The ongoing, global phase 1/2 study showed that rilzabrutinib, a Bruton tyrosine kinase inhibitor specifically developed to treat autoimmune disorders, could be an efficacious and well-tolerated treatment for ITP. Clinical activity, durability of response, and safety were evaluated in 16 responding patients who continued rilzabrutinib 400 mg twice daily in the long-term extension (LTE) study.

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  • The phase 3 ASPEN trial compared the effectiveness of two BTK inhibitors, zanubrutinib and ibrutinib, in treating Waldenström macroglobulinemia, analyzing genetic mutations' impact on treatment response.
  • The study found that patients with mutations in CXCR4 and TP53 had poorer responses and survival rates but those treated with zanubrutinib generally showed better outcomes than those given ibrutinib.
  • Overall, the research indicated that zanubrutinib offers improved clinical outcomes for patients with specific mutations compared to ibrutinib, highlighting the importance of genetic testing in treatment decision-making.
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  • * Glofitamab is a T-cell-engaging bispecific antibody, being tested in the NP30179 trial, showing promising safety and efficacy results in patients with refractory/relapsed B-cell non-Hodgkin lymphoma, including DLBCL.
  • * The phase II results of the NP30179 study have led to glofitamab's global approval for use in relapsed DLBCL, indicating its comparable effectiveness to other treatments and its manageable side effects
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The Lugano 2014 criteria are the standard for response assessment in lymphoma. We compared the prognostic performance of Lugano 2014 and the more recently developed response evaluation criteria in lymphoma (RECIL 2017), which relies primarily on computed tomography and uses unidimensional measurements, in patients with previously untreated diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) from the phase III GOYA and GALLIUM trials, respectively. Concordance between responses according to the Lugano 2014 and RECIL 2017 criteria was analyzed.

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Cell dysplasia is a currently used term describing various cellular developmental abnormalities visible by microscopy. However, detailed description of these developmental abnormalities might provide useful information not only on the cell state but also on the abnormal developmental steps of cell lineages, tissues and organs. The frequently noted visualized cell dysplastic features reflect nuclear- or nucleolar-cytoplasmic anarchy (asynchrony), premature heterochromatin condensation state, marked aneuploidy, abnormal nucleus-cytoplasm ratio, abnormality of cell organelles including mitochondria, abnormal presence or absence of cell lineage-specific granules, and formation of peripheral buds or blebbing on the cell surface.

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The cell body space occupied by the nucleus decreased during the cell differentiation of the granulocytic cell lineage in CML (Chronic Myeloid Leukemia) patients. In contrary, in patients suffering from CLL (Chronic Lymphocytic Leukemia), the cell body space occupied by the nucleus during the cell differentiation of the lymphocytic lineage did not decrease despite the reduction of the cell size. Thus, the cell body space occupied by the cell nucleus during the differentiation was characteristic for each of these cell lineages.

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Background: Parsaclisib, a potent and highly selective PI3Kδ inhibitor, has shown clinical benefit in patients with relapsed or refractory (R/R) B-cell malignancies. This phase 2 study (CITADEL-203; NCT03126019, EudraCT 2017-001624-22) assessed efficacy and safety of parsaclisib monotherapy in patients with R/R follicular lymphoma (FL).

Methods: Patients ≥18 years of age with histologically confirmed R/R FL (grade 1-3a) and prior treatment with ≥2 systemic therapies received parsaclisib 20 mg once daily (QD) for 8 weeks then parsaclisib 20 mg once weekly (weekly dosing group [WG]) or parsaclisib 20 mg QD for 8 weeks then parsaclisib 2.

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Our knowledge of genetic aberrations, that is, variants and copy number variations (CNVs), associated with mantle cell lymphoma (MCL) relapse remains limited. A cohort of 25 patients with MCL at diagnosis and the first relapse after the failure of standard immunochemotherapy was analyzed using whole-exome sequencing. The most frequent variants at diagnosis and at relapse comprised six genes: TP53, ATM, KMT2D, CCND1, SP140, and LRP1B.

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Background: Parsaclisib is a potent and highly selective PI3Kδ inhibitor that has shown clinical benefit in patients with relapsed/refractory (R/R) B-cell malignancies. In this phase 2 study (CITADEL-205; NCT03235544, EudraCT 2017-003148-19), the efficacy and safety of parsaclisib was evaluated in patients with R/R mantle cell lymphoma (MCL).

Methods: Patients ≥18 years old with pathologically confirmed R/R MCL and prior treatment with 1-3 systemic therapies, with (cohort 1) or without (cohort 2) previous Bruton kinase inhibitor (BTKi) treatment, received oral parsaclisib 20 mg once-daily (QD) for 8 weeks, then either parsaclisib 20 mg once-weekly (weekly dosing group [WG]) or parsaclisib 2.

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Patients with relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL) for whom autologous hematopoietic cell transplantation (auto-HCT) had failed experienced frequent and durable responses to nivolumab in the phase 2 CheckMate 205 trial. We present updated results (median follow-up, ∼5 years). Patients with R/R cHL who were brentuximab vedotin (BV)-naive (cohort A), received BV after auto-HCT (cohort B), or received BV before and/or after auto-HCT (cohort C) were administered with nivolumab 3 mg/kg IV every 2 weeks until progression or unacceptable toxicity.

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Purpose: The combination of zanubrutinib plus obinutuzumab (ZO) was found to be well tolerated with an early signal of efficacy in a phase Ib study. ROSEWOOD is a phase II, randomized study that assessed the efficacy and safety of ZO versus obinutuzumab in patients with relapsed/refractory (R/R) follicular lymphoma (FL).

Methods: Patients with R/R FL who had received ≥2 lines of therapy, including an anti-CD20 antibody and an alkylating agent, were randomly assigned 2:1 to receive ZO or obinutuzumab (O).

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Article Synopsis
  • The phase III ASPEN study showed that zanubrutinib is as effective as ibrutinib but has better safety for treating patients with Waldenström macroglobulinemia (WM).
  • In a long-term follow-up, zanubrutinib demonstrated higher rates of very good partial response and complete response compared to ibrutinib in both cohorts of WM patients.
  • Adverse events like diarrhea, muscle spasms, and hypertension were more common with ibrutinib, while zanubrutinib had a lower risk of treatment-related discontinuation.
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Importance: Autologous hematopoietic stem cell transplant (AHSCT) is available for treatment of highly active multiple sclerosis (MS).

Objective: To compare the effectiveness of AHSCT vs fingolimod, natalizumab, and ocrelizumab in relapsing-remitting MS by emulating pairwise trials.

Design, Setting, And Participants: This comparative treatment effectiveness study included 6 specialist MS centers with AHSCT programs and international MSBase registry between 2006 and 2021.

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