Publications by authors named "Cwynarski K"

Previous reports have indicated that during the era of combination antiretroviral therapy, the major causes of morbidity and mortality in people living with HIV (PLWH) were not solely linked to HIV-related opportunistic infections but also to cancers that were difficult to manage due to HIV-related immunodeficiency. We investigated whether PLWH who underwent autologous hematopoietic stem cell transplantation (ASCT) for lymphomas experienced significant morbidity over the past thirty years following HIV infection. We conducted a retrospective follow-up study of 49 PLWH over a 10-year period following ASCT.

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Background: Procarbazine-containing chemotherapy regimens are associated with cytopenias and infertility, suggesting stem-cell toxicity. When treating Hodgkin lymphoma, procarbazine in escalated-dose bleomycin-etoposide-doxorubicin-cyclophosphamide-vincristine-procarbazine-prednisolone (eBEACOPP) is increasingly replaced with dacarbazine (eBEACOPDac) to reduce toxicity. We aimed to investigate the impact of this drug substitution on the mutation burden in stem cells, patient survival, and toxicity.

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Relapsed/refractory peripheral T cell lymphomas (PTCLs) are aggressive tumors with a poor prognosis. Unlike B cell lymphomas, treatment of PTCL has not benefited from advances in immunotherapy. This is largely due to a lack of suitable target antigens that discriminate malignant from normal T cells, thus avoiding severe immunosuppression consequent to depletion of the entire T cell compartment.

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Background: Peripheral T-cell lymphomas are aggressive non-Hodgkin lymphomas with few treatment options for relapsed or refractory disease. Valemetostat tosylate (valemetostat) is a potent, novel, dual inhibitor of EZH2 and EZH1. We investigated the clinical activity and safety of valemetostat in patients with relapsed or refractory peripheral T-cell lymphoma, and its safety in patients with relapsed or refractory adult T-cell leukaemia/lymphoma.

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Article Synopsis
  • The EHA-ESMO Clinical Practice Guideline offers important recommendations for the diagnosis, staging, treatment, and follow-up of HIV-associated lymphomas.
  • It includes insights from a diverse team of experts in oncology from various European institutions.
  • The recommendations are grounded in scientific research and the collective expertise of the authors.
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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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This Good Practice Paper provides recommendations for the baseline investigation, risk stratification and use of prophylactic interventions for patients with large B-cell lymphoma at risk of central nervous system relapse. Recent evidence which has questioned the role of high-dose methotrexate in this clinical scenario is discussed in detail.

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This EHA-ESMO Clinical Practice Guideline provides key recommendations for managing primary DLBCL of the CNS.The guideline covers clinical, imaging and pathological diagnosis, staging and risk assessment, treatment and follow-up.Algorithms for first-line and salvage treatments are provided.

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  • Posttransplant lymphoproliferative disorder (PTLD) is a rare but serious complication in solid organ transplant patients, and chemotherapy can lead to significant side effects.
  • The TIDaL trial tested the safety and effectiveness of ibrutinib, alongside a risk-based treatment strategy, for newly diagnosed patients with CD20+ B-cell PTLD.
  • While ibrutinib did not meet the effectiveness threshold anticipated, the study highlighted the potential to reduce exposure to harsher chemotherapy treatments for patients in the low-risk category, indicating a direction for future research.
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Peripheral T-cell lymphomas are rare heterogeneous haematological malignancies that may also involve peripheral nerves in a very small subset of cases. We report a patient with a diagnostically challenging cutaneous T-cell lymphoma and multifocal mononeuropathies in whom a targeted nerve biopsy identified lymphomatous infiltration of nerves and expedited combination treatment with chemotherapy and an autologous stem cell transplant. She showed an excellent response with a complete metabolic response on positron emission tomography imaging and significant clinical improvement, maintained 5 years post-treatment.

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Central nervous system (CNS) lymphoma has traditionally had very poor outcomes however advances in management have resulted in dramatic improvements and long-term survival of patients. We describe the evidence for treatment strategies for these aggressive disorders. In primary CNS lymphoma there are randomized trial data to inform treatment decisions but these are lacking to guide management in secondary CNS lymphoma.

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Article Synopsis
  • * Involved 523 patients in a randomized trial, results showed significantly less disease progression and death in the ibrutinib-venetoclax group compared to the FCR group over a median follow-up of 43.7 months.
  • * A large percentage of patients on the ibrutinib-venetoclax therapy achieved undetectable levels of measurable residual disease (MRD), indicating better long-term outcomes, while infection rates were
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The success of CD19 Chimeric antigen receptor (CAR) T-cell therapy in large B-cell lymphoma (LBCL) has been partially offset by toxicity and logistical challenges, which off-the-shelf agents like CD20xCD3 bispecific antibodies might potentially overcome. However, when using CAR T outcomes as the 'standard-of-care comparator̕ for relapsed/refractory (r/r) LBCL, a potential learning curve with implementing a novel, complex therapy like CAR T needs to be considered. To address this, we analysed 726 UK patients intended to be treated with CD19 CAR T for r/r LBCL and compared outcomes between the first year of the national CAR T programme (Era 1; 2019) and the more recent treatment era (Era 2; 2020-2022).

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Plasmablastic lymphoma (PBL) is a rare and aggressive non-Hodgkin lymphoma associated with immunodeficiency, characterized by uncertain treatment approaches and an unfavorable prognosis. We conducted a multicenter, international, retrospective cohort study, aiming to characterize the clinical features, risk factors, and outcomes of patients with PBL. Data were collected from 22 institutions across 4 countries regarding patients diagnosed with PBL between 1 January 1999 and 31 December 2020.

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Article Synopsis
  • The study investigates the effectiveness of high-dose methotrexate (HD-MTX) in preventing CNS (central nervous system) progression in high-risk patients with aggressive B-cell lymphoma.
  • It involved over 2,400 patients, comparing those who received HD-MTX to those who did not, and found a lower risk of CNS progression in the overall group but no significant results in patients who had a complete response after initial treatment.
  • Ultimately, the research concluded that HD-MTX did not show a clear benefit in reducing CNS progression risk, with 7.2% of high-risk patients still progressing over two years.
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Secondary central nervous system (CNS) lymphoma (SCNSL) is a rare but clinically challenging scenario with historically disappointing outcomes. SCNSL refers to lymphoma that has spread into the CNS concurrently with systemic disease or CNS relapse during or after frontline immunochemotherapy, presenting with or without systemic lymphoma. Diffuse large B-cell lymphoma (DLBCL) denotes the most common entity, but an increased incidence is observed in other histologies, such as Burkitt lymphoma and mantle-cell lymphoma.

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Purpose Of Review: Central nervous system (CNS) relapse in patients with diffuse large B-cell lymphoma (DLBCL) is an uncommon but devastating complication with an overall survival of less than 6 months. This article will review the recent updates on CNS prophylaxis including new potential advances in the identification of high-risk patients.

Recent Findings: The identification of patients at a high risk of CNS relapse is based on clinical and biological features has improved over recent years; however, the of different CNS prophylaxis strategies including intrathecal chemotherapy and high-dose methotrexate have been recently questioned in several large retrospective studies.

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