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Abstract Hypomethylating agents are the most widely used upfront therapy for patients with myelodysplastic syndrome (MDS) who are not suitable for hematopoietic stem cell transplantation. In Australia, azacitidine was, until recently, the only approved and subsidized treatment for patients with intermediate‐2 and high‐risk MDS, chronic myelomonocytic leukemia, and low blast acute myeloid leukemia. We analyzed prescription data to evaluate the real‐world persistence and overall survival (OS) of patients prescribed azacitidine for the first time in Australia. A retrospective cohort analysis of patients who had been prescribed Pharmaceutical Benefits Scheme (PBS)‐listed azacitidine for the first time, between January 2016 and April 2021, was conducted using the PBS 10% dataset. Treatment persistence and OS were estimated using Kaplan–Meier methods. The impact of the number of treatment cycles and treatment adherence on OS was also estimated. There were 351 patients in the PBS 10% dataset who initiated treatment with azacitidine. The average age (standard deviation [SD]) at azacitidine initiation was 71.9 (11.1) years and the average number (SD) of azacitidine prescriptions was 5.6 (0.2). The median persistence on azacitidine was 15.6 months, and the OS was 13.4 months. The median OS for patients who had six or more cycles of azacitidine treatment was greater compared to patients who had five or less cycles of treatment. The data from this real‐world study illustrate the unmet medical needs of patients with MDS treated with azacitidine in Australia. The majority of patients are not treated with the optimal number of cycles of azacitidine, which is negatively correlated with patient outcomes.

Abstract This study reports the development activities for the Treatment Preference Myelodysplasia Questionnaires (TPMQ) for clinicians (mTPMQ), carers (cTPMQ), and patients (pTPMQ). These tools are intended to evaluate treatment preferences for patients with myelodysplastic syndromes (MDS). This was a non‐interventional, cross‐sectional qualitative interview study consisting of interviews with clinicians, patients, and those caring for patients with MDS. All participants were located in Australia and data were collected from qualitative mixed‐method interviews composed of concept elicitation and cognitive debriefing related to initial drafts of the questionnaires. Fifteen individuals participated in interviews (five from each group). Based on the concept elicitation portion of interviews, concepts of importance were classified and reasons for treatment preference were documented. From cognitive debriefing, the questionnaires were generally deemed to be clear and easy to understand. Participant input from both concept elicitation and cognitive debriefing portions was used to revise initial drafts of the questionnaires. The mTPMQ, cTPMQ, and pTPMQ were developed with direct input from clinicians, patients, and caregivers to assess the key concepts of interest related to the preference for the treatment of MDS and are ready to be used and evaluated further in clinical trials.

Abstract Despite an increasing desire to use historical cohorts as “synthetic” controls for new drug evaluation, limited data exist regarding the comparability of real-world outcomes to those in clinical trials. Governmental cancer data often lacks details on treatment, response, and molecular characterization of disease sub-groups. The Australasian Leukaemia and Lymphoma Group National Blood Cancer Registry (ALLG NBCR) includes source information on morphology, cytogenetics, flow cytometry, and molecular features linked to treatment received (including transplantation), response to treatment, relapse, and survival outcome. Using data from 942 AML patients enrolled between 2012–2018, we assessed age and disease-matched control and interventional populations from published randomized trials that led to the registration of midostaurin, gemtuzumab ozogamicin, CPX-351, oral azacitidine, and venetoclax. Our analyses highlight important differences in real-world outcomes compared to clinical trial populations, including variations in anthracycline type, cytarabine intensity and scheduling during consolidation, and the frequency of allogeneic hematopoietic cell transplantation in first remission. Although real-world outcomes were comparable to some published studies, notable differences were apparent in others. If historical datasets were used to assess the impact of novel therapies, this work underscores the need to assess diverse datasets to enable geographic differences in treatment outcomes to be accounted for.

The mechanisms underlying the pathogenesis of vaccine-induced immune thrombotic thrombocytopenia (VITT) remain unclear. Here the authors show that anti-PF4 antibodies are responsible for the activation of platelets and neutrophils, and blockage of FcγRIIa or NETosis in vivo can prevent thrombosis.

Microparticles (MPs) are small fragments of membrane-bound cytoplasm that are shed from the surface of an activated or apoptotic cell. Recently, their function as vectors of transcellular exchange of biologic information, in addition to better described forms of intercellular communication such as growth factors, cytokines, and chemokines, has become well recognized. Circulating levels of MPs are thought to reflect a balance between cell stimulation, proliferation, and death. The production of MPs is thought to predominately occur by vesiculation or blebbing of the cell membrane. The mechanisms governing the remodeling of the plasma membrane are complex, involving cytoskeletal changes and a shift from normal phospholipid asymmetry. Increased intracellular calcium subsequent to cell activation leads to intracellular increases in several proteins including gelsolin and calpain, as well as the activity of enzymes such as translocase, floppase, and scramblase, which play important roles in the homeostasis of the cell membrane. The membrane vesiculation and phospholipids asymmetry leading to the production of MPs occurs by the complex interplay of the proteins involved. There are several clinical conditions associated with elevated MPs, and most are also associated with an increased risk of thrombosis. Apart from cardiovascular disease and venous thromboembolism, MPs are also elevated in solid tumors with metastatic disease. The measurement of MPs is being regarded as a potential biomarker, given the range of conditions in which they are elevated and the association with prothrombotic states. The utility of measuring MPs as a diagnostic and prognostic marker is currently a subject of intense investigation. The further development of the various methods for the detection and measurement of MPs and prospective clinical trials establishing the utility of such tests will be critical prior to the routine measurement of MPs in the diagnostic laboratory. [ABSTRACT FROM AUTHOR]

Microparticles are small, membrane-bound vesicles that are generated from cells of different origin. It now appears that all circulating blood cells as well as endothelial cells release membranous fragments ~1 ?m in size or smaller bearing at least some characteristics of the parent cell. Elevated levels of microparticles have been described in cardiovascular states, thrombotic conditions, and cancer. Various methods of detection for microparticles include flow cytometry, enzyme-linked immunoassays, and functional assays. Flow cytometry has several advantages including its ability to quantitate and identify microparticles of different cellular origin. However, the standardization of preanalytical and analytical variables for enumeration of microparticles remains a significant challenge. Newer approaches are being investigated, and an international collaboration is working on standardization of detection as well as quantitation of microparticles by flow cytometry. Although it has evolved as an important vascular biology research tool, microparticle detection needs further evaluation and refinement before it becomes truly useful as a clinical tool. [ABSTRACT FROM AUTHOR]