Publications by authors named "KUSS B"

Haemophagocytic lymphohistiocytosis (HLH) is a rare complication of immune checkpoint inhibitor therapy. A 55-year-old male with stable chronic lymphocytic leukemia presented with fevers and symptomatic anaemia after nine cycles of nivolumab for metastatic melanoma. Investigations were consistent with autoimmune haemolytic anemia and corticosteroids were initiated.

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Article Synopsis
  • - Chronic lymphocytic leukaemia (CLL) is the most common blood cancer in Australia and New Zealand, with significant advancements in diagnosis and treatment in the past decade.
  • - New technologies like next-generation sequencing and flow cytometry help doctors predict outcomes and monitor treatment responses more effectively, while new therapies have improved care for patients, especially those with high-risk genetic issues.
  • - Given the unique healthcare landscape in Australasia, experts have created a consensus practice statement to provide standardized guidelines for CLL diagnosis and management, keeping in mind public health concerns like the COVID-19 pandemic.
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Cholesterol has many critical functions in cells. It is a key component of membranes and cell-signalling processes, and it functions as a chemical precursor in several biochemical pathways, such as Vitamin D and steroid synthesis. Cholesterol has also been implicated in the development and progression of various cancers, in which it is thought to promote cell proliferation, migration, and invasion.

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Purpose: The CAPTIVATE study investigated first-line ibrutinib plus venetoclax for chronic lymphocytic leukemia in 2 cohorts: minimal residual disease (MRD)-guided randomized discontinuation (MRD cohort) and Fixed Duration (FD cohort). We report outcomes of fixed-duration ibrutinib plus venetoclax in patients with high-risk genomic features [del(17p), TP53 mutation, and/or unmutated immunoglobulin heavy chain (IGHV)] in CAPTIVATE.

Patients And Methods: Patients received three cycles of ibrutinib 420 mg/day then 12 cycles of ibrutinib plus venetoclax (5-week ramp-up to 400 mg/day).

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Ibrutinib is a small molecule inhibitor of Bruton's tyrosine kinase indicated for the treatment of relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and mantle cell lymphoma (MCL). The Named Patient Program in Australia and New Zealand (ANZ NPP) provided access to ibrutinib treatment to 1126 R/R CLL/SLL and 330 R/R MCL patients, prior to Pharmaceutical Benefits Scheme listing. This study aimed to assess the duration of treatment for the ANZ NPP patients, as an indicator of efficacy and tolerability of ibrutinib in the real world.

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Background: Poor diet may contribute to deleterious chronic health among individuals incarcerated. Yet, limited research has evaluated the nutritional content of menus and commissary items provided in jails. Thus, this study assessed the macronutrient distribution, caloric composition, and diet quality of the seven-day cycle menu and commissary items provided in a southwest, rural county jail in the United States.

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Treatment of chronic lymphocytic leukemia (CLL) has been transformed in the past two decades. The introduction of targeted therapies has improved patient outcomes and the deliverability of effective therapies. Making the best use of the next wave of Bruton's tyrosine kinase (BTK) inhibitors requires an understanding of the nuances that separate the drugs in this class of agents.

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Article Synopsis
  • CAPTIVATE (NCT02910583) is a phase 2 study targeting patients under 70 with untreated chronic lymphocytic leukemia, examining a fixed-duration treatment approach using ibrutinib and venetoclax.
  • Patients received an initial lead-in phase of ibrutinib followed by a combination therapy, leading to a 56% complete response rate in those without a specific genetic deletion (del(17p)), surpassing their target of 37%.
  • The treatment showed strong efficacy, with high rates of undetectable minimal residual disease and excellent survival statistics, while maintaining a good safety profile despite some adverse events like neutropenia and hypertension.
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Many cancers rely on glucose as an energy source, but it is becoming increasingly apparent that some cancers use alternate substrates to fuel their proliferation. Chronic lymphocytic leukaemia (CLL) is one such cancer. Through the use of flow cytometry and confocal microscopy, low levels of glucose uptake were observed in the OSU-CLL and HG3 CLL cell lines relative to highly glucose-avid Raji cells (Burkitt's lymphoma).

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Purpose: This paper determined sodium provisions from a seven-day cycle menu and commissary at a rural Southwest County jail and compared it to Dietary Reference Intakes (DRI) and Dietary Approaches to Stop Hypertension (DASH) recommendations for sodium.

Design/methodology/approach: A seven-day cycle menu and commissary items were used to determine sodium content for each meal and commissary pack. Estimates for the menu and commissary packs paired with the menu (commissary scenarios) were converted to a daily average of sodium and compared to DRI and DASH recommendations.

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Peripheral T-cell lymphomas (PTCL) represent a heterogeneous disease group accounting for 10% of non-Hodgkin lymphomas. PTCL patients have typically poorer outcomes compared with aggressive B-cell lymphomas. However, such outcomes are heavily dependent on subtype.

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Purpose: CAPTIVATE (NCT02910583), a randomized phase II study, evaluates minimal residual disease (MRD)-guided treatment discontinuation following completion of first-line ibrutinib plus venetoclax treatment in patients with chronic lymphocytic leukemia (CLL).

Methods: Previously untreated CLL patients age < 70 years received three cycles of ibrutinib and then 12 cycles of combined ibrutinib plus venetoclax. Patients in the MRD cohort who met the stringent random assignment criteria for confirmed undetectable MRD (Confirmed uMRD) were randomly assigned 1:1 to double-blind placebo or ibrutinib; patients without Confirmed uMRD (uMRD Not Confirmed) were randomly assigned 1:1 to open-label ibrutinib or ibrutinib plus venetoclax.

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Covalent Bruton tyrosine kinase inhibitors (BTKi's) and the B-cell lymphoma 2 (BCL2) inhibitor venetoclax have significantly improved outcomes for patients with chronic lymphocytic leukemia (CLL), especially those with biologically adverse disease. Patients with CLL resistant to their first targeted agent (TA) can be effectively treated with the alternative class. However, relapses are expected with second-line TA therapy, and the clinical challenge of double class-resistant disease is now emerging with increasing frequency.

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The clinical significance of low-frequency deletions of 17p13 [tumour protein p53 (TP53)] in patients with chronic lymphocytic leukaemia (CLL) is currently unclear. Low-frequency del17p clones (<25%) were identified in 15/95 patients in the Australasian Leukaemia and Lymphoma Group (ALLG)/CLL Australian Research Consortium (CLLARC) CLL5 trial. Patients with low del17p, without tumour protein p53 (TP53) mutation, had significantly longer progression-free survival and overall survival durations than patients with high del17p clones.

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Chronic lymphocytic leukaemia (CLL) is a malignant lymphoproliferative disorder characterised by the accumulation of dysfunctional B-lymphocytes in the blood and lymphoid tissues. It is a clonally complex disease with a high degree of both intra-tumoural and inter-patient heterogeneity. This variability leads to a wide range of clinical outcomes and highlights the critical need for accurate prognostic tests in CLL.

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Article Synopsis
  • Covalent BTK inhibitors are effective for B-cell malignancies, but patients often stop using them due to resistance or side effects, prompting the evaluation of pirtobrutinib, a new reversible BTK inhibitor.
  • In a phase 1/2 trial with 323 patients, pirtobrutinib showed no dose-limiting toxicities and the recommended dose was established at 200 mg daily, with some reported side effects like fatigue and diarrhea.
  • Among patients with chronic lymphocytic leukemia or small lymphocytic lymphoma who previously used other BTK inhibitors, pirtobrutinib demonstrated a 62% overall response rate, indicating significant efficacy even in those who previously experienced treatment resistance or intolerance.*
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Cell-free DNA (cfDNA) consists of fragments of double stranded DNA that are found in the circulation. They are released from the apoptosis of both normal haemopoietic cells and malignant cells. The use of cfDNA from easily accessible peripheral blood samples has created a new strategy in studying molecular genomics in haematological malignancies.

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The treatment of chronic lymphocytic leukaemia has been revolutionised in recent years, first by the introduction of chemoimmunotherapy regimens and subsequently by the development of drugs, including ibrutinib, idelalisib and venetoclax, that target components of the B-cell receptor signalling pathway or B-cell lymphoma 2 family of proteins. Despite high initial response rates in patients treated with chemoimmunotherapy or targeted agents, a significant proportion of patients relapse with progressive and refractory disease. In a subset of these patients, drug resistance has been associated with specific genetic lesions or activation of alternate pro-survival pathways.

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Highly active BTK inhibitors (BTKis) and the BCL2 inhibitor venetoclax have transformed the therapeutic landscape for chronic lymphocytic leukemia (CLL). Results of prospective clinical trials demonstrate the efficacy of venetoclax to salvage patients with disease progression on BTKis, but data on BTKi therapy after disease progression on venetoclax are limited, especially regarding durability of benefit. We retrospectively evaluated the records of 23 consecutive patients with relapsed/refractory CLL who received a BTKi (ibrutinib, n = 21; zanubrutinib, n = 2) after stopping venetoclax because of progressive disease.

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Objective: Major trauma is associated with blood loss and hypothermia. It is common to replace lost fluid with red cells stored at 2-6°C, and/or colloid/crystalloid fluid stored at ambient temperature, thus increasing hypothermia risk. At trauma and medical retrieval sites, mains electricity powered fluid warmers cannot be generally used.

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Cardiac amyloidosis is a progressive disorder and is sometimes difficult to diagnose even when suspected in the appropriate clinical setting. We present an interesting case of rapidly progressive light-chain cardiac amyloidosis and highlights the importance of close monitoring even when the initial biopsy and imaging findings are not pathognomonic for amyloidosis. ().

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Purpose: In the phase III DUO trial, duvelisib, an oral dual PI3K-δ,γ inhibitor, demonstrated significantly improved efficacy versus ofatumumab [median (m) progression-free survival (PFS), 13.3 vs. 9.

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Chronic lymphocytic leukaemia (CLL) remains the most common incurable malignancy of B cells in the western world. Patient outcomes are heterogeneous and can be difficult to predict with current prognostic markers. Here, we used a quantitative label-free proteomic technique to ascertain differences in the B-cell proteome from healthy donors and CLL patients with either mutated (M-CLL) or unmutated (UM-CLL) IGHV to identify new prognostic markers.

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