Real-world impact of primary immune thrombocytopenia and treatment with thrombopoietin receptor agonists on quality of life based on patient-reported experience: Results from a questionnaire conducted in Switzerland, Austria, and Belgium.

AIMS OF THE STUDY Thrombopoietin receptor agonists (TPO-RAs) are approved for immune thrombocytopenia (ITP), but their impact on health-related quality of life (HRQoL) remains poorly investigated in clinical practice. This observational study aimed to gain insight into real-world patient-reported experiences of the burden of ITP and TPO-RAs. METHOD An online questionnaire of closed questions was used to collect views of patients with primary ITP from Switzerland, Austria, and Belgium, between September 2018 and April 2020. RESULTS Of 46 patients who completed the questionnaire (total cohort), 41% were receiving TPO-RAs. A numerically higher proportion of patients reported being free from symptoms at the time of the questionnaire (54%) than at diagnosis (24%), irrespective of treatment type. Bleeding, the most frequently reported symptom at diagnosis (59%), was reduced at the time of the questionnaire (7%). Conversely, fatigue was reported by approximately 40% of patients at both diagnosis and the time of the questionnaire. Having a normal life and their disease under control was reported by 83% and 76%, respectively, but 41% were worried/anxious about their condition. Nearly 50% reported that ITP impaired their engagement in hobbies/sport or energy levels and 63% reported no impact on employment. When stratified by TPO-RA use, bleeding was better controlled in those receiving TPO-RAs than not (0% vs 11%). A numerically lower proportion receiving TPO-RAs than not reported worry/anxiety about their condition (16% vs 59%) and shifting from full-time to part-time employment (11% vs 22%). Similar proportions were satisfied with their therapy whether they were receiving TPO-RAs or not (89% vs 85%). CONCLUSIONS Many factors affect HRQoL in patients with ITP. Of patients receiving TPO-RAs, none experienced bleeding at the time of the questionnaire; they also showed a more positive perspective for some outcomes than those not using TPO-RAs. However, fatigue was not reduced by any treatment

Immunomodulation with romiplostim as a second-line strategy in primary immune thrombocytopenia: The iROM study.

Thrombopoietin receptor agonists (TPO-RAs) stimulate platelet production, which might restore immunological tolerance in primary immune thrombocytopenia (ITP). The iROM study investigated romiplostim's immunomodulatory effects. Thirteen patients (median age, 31 years) who previously received first-line treatment received romiplostim for 22 weeks, followed by monitoring until week 52. In addition to immunological data, secondary end-points included the sustained remission off-treatment (SROT) rate at 1 year, romiplostim dose, platelet count and bleedings. Scheduled discontinuation of romiplostim and SROT were achieved in six patients with newly diagnosed ITP, whereas the remaining seven patients relapsed. Romiplostim dose titration was lower and platelet count response was stronger in patients with SROT than in relapsed patients. In all patients, regulatory T lymphocyte (Treg) counts increased until study completion and the counts were higher in patients with SROT. Interleukin (IL)-4, IL-9 and IL-17F levels decreased significantly in all patients. FOXP3 (Treg), GATA3 (Th2) mRNA expression and transforming growth factor-β levels increased in patients with SROT. Treatment with romiplostim modulates the immune system and possibly influences ITP prognosis. A rapid increase in platelet counts is likely important for inducing immune tolerance. Better outcomes might be achieved at an early stage of autoimmunity, but clinical studies are needed for confirmation

Diagnostik und Therapie myelodysplastischer Syndrome

Diagnosis and treatment of myelodysplastic syndromes The myelodysplastic syndromes (MDS) are heterogeneous clonal disorders of the hematopoietic stem cells and affect mainly elderly people from the 7th decade of life. Management of MDS patients is challenging due to the broad spectrum of presentations and courses of the disease, varying from chronic cytopenia to rapid progression towards acute myeloid leukaemia (AML). The incidence and prevalence of MDS is expected to increase due to ageing of the population. Therefore, MDS is assumed to become one of the most important haematologic malignancies with an emerging impact on future healthcare costs. The only curative treatment is an allogeneic hematopoietic stem cell transplantation for which only a minority of patients is eligible. This review shall provide an update for practicing hemato-oncologists on the current understanding of pathophysiology as well as the recommendations for diagnosis and treatment of this emerging disease

Rituximab for acute plasma-refractory thrombotic thrombocytopenic purpura. A case report and concise review of the literature

Thrombotic thrombocytopenic purpura (TTP) is a rare disease which responds well to plasma exchange treatment in the majority of patients. We report on a patient with acute TTP caused by severe autoantibody-mediated ADAMTS-13 deficiency, in whom remission was not achieved by initial treatment consisting of plasma exchange (PE), plasma infusion and corticosteroids, followed by vincristine and splenectomy. In view of the ongoing activity of TTP, treatment was initiated with rituximab, a chimaeric monoclonal antibody directed against the CD 20 antigen present on B lymphocytes. The patient received 4 weekly infusions of 375 mg/m2, each administered after the daily PE session and withholding PE until 48 hours later. Three weeks after the last infusion of rituximab a complete clinical and laboratory remission of this first episode of acute refractory TTP was documented. A concise review of the literature on the role of rituximab in patients with a first episode of acute plasma-refractory TTP suggests that rituximab in that situation may produce clinical remission in a significant proportion of patients, result in a lowered plasma requirement and avoid the complications of salvage immunosuppressive therapy. The use of rituximab in acute refractory TTP appears to be safe, with no excess infectious complications. We conclude that rituximab should be considered in TTP patients with acquired ADAMTS-13 deficiency who fail to respond clinically after 7-14 days of standard treatment with daily PE and glucocorticoids

Final report : studies of freshwater inflow effects on the Lavaca River Delta and Lavaca Bay, Texas

The Texas Water Development Board (TWDB) is concerned with management of surface freshwater resources. They must plan on water use by urban populations, industry, and agriculture. In addition they must also consider the needs of Texas bays and estuaries that have evolved to receive freshwater input. In order to better understand these needs, the TWDB has been conducting and sponsoring research on the freshwater requirements of bays and estuaries in both impounded and non-impounded drainage basins. The TWDB contracted with the University of Texas at Austin's Marine Science Institute (UTMSI) for one such project. Officials from TWDB and UTMSI met and worked out the components of a two year, multidisciplinary study on selected sites in the upper Lavaca-Tres Palacios Estuary and parts of Matagorda Bay. Data were collected on 14 sampling trips between November 1984 and August 1986. The primary goals were to obtain an environmental assessment of the upper Lavaca Bay after completion of the Palmetto Bend reservoir project on the Navidad River (dam closed in 1980, forming Lake Texana); and to document the use of the lower river delta as a nursery area for finfish and shellfish. The study had several components that are reported as separate chapters within this report. The broad objective of this and similar studies is addressed by three questions. What happens when freshwater is introduced into the estuary? What happens when freshwater is withheld from the estuary? How much freshwater must be introduced to forestall the negative effects of withholding it? These questions have little meaning unless there is a clear understanding of what processes are being studied and what temporal and spatial scales are being considered. There is a crucial relationship between the scales of physical forcing and biological response that is dependent on the generation times and mobilities of the organisms in question (Haury et al. 1979; Lewis and Platt 1982). Because the diverse biological components of an estuarine ecosystem have vastly different lifespans and capacity for movement, the answers to the three questions above would depend in large part on ecological perspective. A reasonable approach would be to look at the temporal scale of a year and the spatial scale encompassing the drainage basin. Appropriate biological components for study would include larger organisms that integrate their environment and may have some economic importance: finfish, shrimp, and benthic macrofauna. Unfortunately, many of the effects of physical forcing (i.e. freshwater input) on higher trophic levels are likely to be indirectly expressed through influences on the productivity and taxonomic composition of food resources. So, to answer our three questions in the appropriate context for management (relatively long term, large scale, higher trophic levels), it is necessary to answer the same questions for lower trophic levels on appropriate scales for each biological component. In addition, the nature of biological coupling between producers and consumers must be determined. For example, what is the relationship between primary production and fish production? The problem assumes immense proportions. Ideally, a study of the freshwater requirements of an estuary would look at statistical relationships between state variables (e.g. salinity, chlorophyll, zooplankton abundance, fisheries yield) and also the dynamic processes linking the variables (e.g. light-limitation of primary production, feeding habits of juvenile fish, etc.). This two-year study with approximately bimonthly sampling was by necessity constrained. Systematic sampling provided good records of a large number of variables over limited temporal and spatial scales but process-oriented studies were beyond the scope of the contract. Many process-oriented questions are now being addressed in a project recently initiated in San Antonio Bay.From the University of Texas at Austin Marine Science Institute, Port Aransas, Texas ... to Texas Water Development Board ... Austin, Texas ...December 1986Marine Scienc