Publications by authors named "Renata Walewska"
The recognition of B-cell prolymphocytic leukemia (B-PLL) as a separate entity is controversial based on the current classification systems. Here, we analyzed the DNA methylome of a cohort of 20 B-PLL cases diagnosed according to the guidelines of the International Consensus Classification/Fourth revised edition of the World Health Organization Classification, and compared them with chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), splenic marginal zone lymphoma (SMZL), and normal B-cell subpopulations. Unsupervised principal component analyses suggest that B-PLL is epigenetically distinct from CLL, MCL, and SMZL, which is further supported by robust differential methylation signatures in B-PLL.
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- * The disease's development is influenced by both the tumor microenvironment and inherent genetic changes, with notable chromosomal abnormalities and recurring mutations linked to B-cell differentiation.
- * Current research reveals distinct patient subgroups based on genetic and epigenetic features, which can inform treatment strategies and improve patient management in the future.
Venetoclax, a highly selective, oral B-cell lymphoma 2 inhibitor, provides a robust targeted-therapy option for the treatment of chronic lymphocytic leukemia (CLL), including patients with high-risk del(17p)/mutated- and immunoglobulin heavy variable region unmutated CLL and those refractory to chemoimmunotherapy across all age groups. Due to the potent pro-apoptotic effect of venetoclax, treatment initiation carries a risk of tumor lysis syndrome (TLS). Prompt and appropriate management is needed to limit clinical TLS, which may entail serious adverse events and death.
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- * 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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- Patients with chronic lymphocytic leukemia (CLL) have a significantly heightened risk of developing other malignancies (OMs), with a study tracking nearly 20,000 CLL patients revealing 3,513 OMs diagnosed over 129,254 years of follow-up.
- The study found that treatment with fludarabine and cyclophosphamide increased the likelihood of developing myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), while non-melanoma skin cancer (NMSC) and prostate cancer were common solid tumors in treated patients.
- Importantly, patients with CLL who developed OMs had lower overall survival rates, especially those diagnosed with AML and MDS, highlighting that C
Background: The approval of Bruton tyrosine kinase (BTK) inhibitors in patients with previously untreated chronic lymphocytic leukaemia (CLL) was based on trials which compared ibrutinib with alkylating agents in patients considered unfit for fludarabine, cyclophosphamide, and rituximab, the most effective chemoimmunotherapy in CLL. We aimed to assess whether ibrutinib and rituximab is superior to fludarabine, cyclophosphamide, and rituximab in terms of progression-free survival.
Methods: This study is an interim analysis of FLAIR, which is an open-label, randomised, controlled, phase 3 trial in patients with previously untreated CLL done at 101 UK National Health Service hospitals.
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- Patients with chronic lymphocytic leukemia (CLL) on ibrutinib treatment often develop resistance due to mutations in the BTK and PLCG2 genes, with varying frequencies impacting patient outcomes.
- A study of 98 CLL patients revealed that 65% of those who relapsed exhibited at least one mutation in BTK or PLCG2, while 12% of responding patients also had mutations, indicating a potential for progression.
- The findings suggest that other genetic mutations may contribute to resistance, with BTK mutation profiles differing between relapsing patients, but no significant impact on TP53 mutations was observed, highlighting the complexity of treatment resistance.
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- - Splenic marginal zone B-cell lymphoma (SMZL) is a complex condition with varying clinical outcomes, influenced by multiple gene mutations and diverse regulatory pathways, making it critical to identify different subgroups based on their genetic and environmental features.
- - Researchers analyzed 303 spleen samples from an international study to understand these subgroups, ultimately identifying two main genetic clusters: NNK (58% of cases) and DMT (32% of cases), each with unique genetic profiles and survival outcomes.
- - The study revealed two types of immune microenvironments within SMZL: immune-suppressive and immune-silent, highlighting their distinct clinical implications and the potential for improving classification and targeted therapies in this disease.
Given advanced age, comorbidities, and immune dysfunction, chronic lymphocytic leukemia (CLL) patients may be at particularly high risk of infection and poor outcomes related to coronavirus disease 2019 (COVID-19). Robust analysis of outcomes for CLL patients, particularly examining effects of baseline characteristics and CLL-directed therapy, is critical to optimally manage CLL patients through this evolving pandemic. CLL patients diagnosed with symptomatic COVID-19 across 43 international centers (n = 198) were included.
View Article and Find Full Text PDFBackground: Acalabrutinib is a selective, covalent Bruton tyrosine-kinase inhibitor with activity in chronic lymphocytic leukaemia. We compare the efficacy of acalabrutinib with or without obinutuzumab against chlorambucil with obinutuzumab in patients with treatment-naive chronic lymphocytic leukaemia.
Methods: ELEVATE TN is a global, phase 3, multicentre, open-label study in patients with treatment-naive chronic lymphocytic leukaemia done at 142 academic and community hospitals in 18 countries.
Despite advances in chronic lymphocytic leukaemia (CLL) treatment, globally chemotherapy remains a central treatment modality, with chemotherapy trials representing an invaluable resource to explore disease-related/genetic features contributing to long-term outcomes. In 499 LRF CLL4 cases, a trial with >12 years follow-up, we employed targeted resequencing of 22 genes, identifying 623 mutations. After background mutation rate correction, 11/22 genes were recurrently mutated at frequencies between 3.
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- - Elderly CLL patients (>75 years) experience more toxicity from ibrutinib compared to younger patients, but the safety of venetoclax in older patients is unclear.
- - This study analyzes safety and efficacy data from 342 CLL patients aged 75 and older versus those under 75, focusing on non-trial treatment settings.
- - Results indicate that venetoclax is equally effective and safe for elderly patients, many of whom have already been treated with ibrutinib and have limited treatment options.
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