Publications by authors named "Michael F Leahy"

Background: The COVID-19 pandemic has significantly impacted people with cancer. Initial vaccine studies excluded patients with malignancy. Immunocompromised individuals remain vulnerable to SARS-CoV-2, necessitating detailed understanding of vaccine response.

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In newly diagnosed transplant-ineligible patients with myeloma, daratumumab has improved outcomes when added to the standard-of-care regimens. In a randomized trial, we tested whether similar improvements would be observed when daratumumab was added to the bortezomib, cyclophosphamide, and dexamethasone (VCD) regimen. Transplant-ineligible patients with untreated myeloma were randomized to receive VCD or VCD plus daratumumab (VCDD).

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Article Synopsis
  • - Patients with myelofibrosis suffer from various symptoms due to bone marrow fibrosis and inflammation, and improving these symptoms can enhance their quality of life.
  • - This study analyzed data from two phase III trials of momelotinib (SIMPLIFY-1 and SIMPLIFY-2) to determine a meaningful change threshold (MCT) for symptoms, finding it to be 8 points for treatment-naive patients and 6 points for those previously treated.
  • - Results showed that momelotinib effectively improved patient symptoms, suggesting that the traditional 50% reduction standard used in clinical trials may be too conservative and that momelotinib offers significant benefits compared to other treatments in myelofibrosis patients.
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Transcription factor 3 (TCF3) is a DNA transcription factor that modulates megakaryocyte development. Although abnormal TCF3 expression has been identified in a range of hematological malignancies, to date, it has not been investigated in myelofibrosis (MF). MF is a Philadelphia-negative myeloproliferative neoplasm (MPN) that can arise or progress from essential thrombocythemia [ET] and polycythemia vera [PV] and where dysfunctional megakaryocytes have a role in driving the fibrotic progression.

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Article Synopsis
  • Myelofibrosis (MF) is a chronic condition causing severe symptoms, particularly fatigue and anemia, which greatly affect patients' quality of life.
  • The JAK1/JAK2/activin A receptor type 1 inhibitor momelotinib has shown promising results in clinical trials, significantly improving both anemia and overall MF-related symptoms compared to danazol.
  • The phase 3 MOMENTUM trial confirmed these benefits, with patients on momelotinib experiencing faster and lasting symptom relief, particularly in fatigue and physical functioning, as demonstrated by various patient-reported outcome measures.
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Platelets are small circulating fragments of cells that play important roles in thrombosis, haemostasis, immune response, inflammation and cancer growth. Although anucleate, they contain a rich RNA repertoire which offers an opportunity to characterise changes in platelet gene expression in health and disease. Whilst this can be achieved with conventional RNA sequencing, a large input of high-quality RNA, and hence blood volume, is required (unless a pre-amplification step is added), along with specialist bioinformatic skills for data analysis and interpretation.

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Article Synopsis
  • Myelofibrosis (MF) causes significant health-related quality of life issues, and traditional clinical trials often use a basic measure of symptom improvement, which may not capture the full range of patient experiences.
  • This study used advanced statistical methods to analyze how symptoms change over a 24-week period in patients with MF treated with momelotinib, comparing these changes to a control group.
  • Results showed that both momelotinib and ruxolitinib improved overall symptoms, but momelotinib consistently led to better outcomes, with more patients reporting improvements or stability compared to the control group.
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Background: Most patients transfused red blood cells in elective surgery receive small volumes of blood, which is likely to be discretionary and avoidable. We investigated the outcomes of patients who received a single unit of packed red blood cells during their hospital admission for an elective surgical procedure when compared to those not transfused.

Methods: This retrospective cohort study included elective surgical admissions to 4 hospitals in Western Australia over a 6-year period.

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Jumping translocations (JT) are rare chromosomal rearrangements caused by the translocation of one donor chromosome segment to two or more recipient chromosomes. In the setting of myeloid neoplasms, JT are typically associated with disease transformation to acute myeloid leukemia (AML), and studies to date have found JT to be associated with poor prognosis and short overall survival. However, JT have been only very rarely reported in AML associated with a favorable AML prognostic cytogenetic marker.

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Background: Predicting red cell transfusion may assist in identifying those most likely to benefit from patient blood management strategies. Our objective was to identify a simple statistical model to predict transfusion in elective surgery from routinely available data.

Materials And Methods: Our final multicentre cohort consisted of 42,546 patients and contained the following potential predictors of red cell transfusion known prior to admission: patient age, sex, pre-admission hemoglobin, surgical procedure, and comorbidities.

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Objectives: The ability to predict in-hospital mortality from data available at hospital admission would identify patients at risk and thereby assist hospital-wide patient safety initiatives. Our aim was to use modern machine learning tools to predict in-hospital mortality from standardized data sets available at hospital admission.

Methods: This was a retrospective, observational study in 3 adult tertiary care hospitals in Western Australia between January 2008 and June 2017.

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Objective: Obesity is a risk factor for developing venous thromboembolism (VTE). Optimal dosage of enoxaparin has not been established in the obese population. We aimed to study clinical outcomes and complications with enoxaparin in obese patients.

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Background: In 2016, a preoperative clinic was implemented to screen, evaluate, and manage anemia and suboptimal iron stores at a major tertiary care medical center in Western Australia. Few studies compare the costs and reimbursements associated with preoperative anemia and suboptimal iron stores management. The objective of our study was to conduct a net cost analysis associated with the implementation of this clinic.

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Zanubrutinib (BGB-3111) is a next-generation Bruton tyrosine kinase inhibitor designed to be more selective with fewer off-target effects. We conducted a phase 1 study to assess the safety of its combination with obinutuzumab and evaluate early efficacy in 81 patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) or relapsed/refractory (R/R) follicular lymphoma (FL). In this phase 1b study, zanubrutinib was tolerable at 160 mg twice daily or 320 mg once daily combined with IV obinutuzumab in patients with CLL/SLL (n = 45) and FL (n = 36).

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Chronic lymphocytic leukaemia is a slow-growing leukaemia of developing B-lymphocytes, which may transform to an aggressive lymphoma known as Richter's syndrome. While Richter's syndrome can present in untreated or relapsed-refractory cases, it may occur upon the commencement of less intensity treatment regimens. We present a case of Richter's syndrome following treatment with chlorambucil and obinutuzumab and review of available literature on the topic.

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Background: The ability to predict transfusions arising during hospital admission might enable economized blood supply management and might furthermore increase patient safety by ensuring a sufficient stock of red blood cells (RBCs) for a specific patient. We therefore investigated the precision of four different machine learning-based prediction algorithms to predict transfusion, massive transfusion, and the number of transfusions in patients admitted to a hospital.

Study Design And Methods: This was a retrospective, observational study in three adult tertiary care hospitals in Western Australia between January 2008 and June 2017.

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Background: There are no overviews of systematic reviews investigating haemoglobin thresholds for transfusion. This is important as the literature on transfusion thresholds has grown considerably in recent years. Our aim was to synthesise evidence from systematic reviews and meta-analyses of the effects of restrictive and liberal transfusion strategies on mortality.

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We report a rare case of aggressive plasmablastic lymphoma with an initial presentation of dermatomyositis. The challenges associated with the diagnosis and treatment approach are also highlighted in this case report.

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The World Health Organization (WHO) has declared coronavirus disease 2019 (COVID-19), the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a pandemic. Global health care now faces unprecedented challenges with widespread and rapid human-to-human transmission of SARS-CoV-2 and high morbidity and mortality with COVID-19 worldwide. Across the world, medical care is hampered by a critical shortage of not only hand sanitizers, personal protective equipment, ventilators, and hospital beds, but also impediments to the blood supply.

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