Risk Factors for Alloimmunisation after red blood Cell Transfusions (R-FACT): a case cohort study

INTRODUCTION: Individuals exposed to red blood cell alloantigens through transfusion, pregnancy or transplantation may produce antibodies against the alloantigens. Alloantibodies can pose serious clinical problems such as delayed haemolytic reactions and logistic problems, for example, to obtain timely and properly matched transfusion blood for patients in which new alloantibodies are detected. OBJECTIVE: The authors hypothesise that the particular clinical conditions (eg, used medication, concomitant infection, cellular immunity) during which transfusions are given may contribute to the risk of immunisation. The aim of this research was to examine the association between clinical, environmental and genetic characteristics of the recipient of erythrocyte transfusions and the risk against erythrocyte alloimmunisation during that transfusion episode. METHODS AND ANALYSIS STUDY DESIGN: Incident case-cohort study. SETTING: Secondary care, nationwide study (within the Netherlands) including seven hospitals, from January 2005 to December 2011. STUDY POPULATION: Consecutive red cell transfused patients at the study centres. INCLUSION: The study cohort comprises of consecutive red blood cell transfused patients at the study centre. EXCLUSION: Patients with transfusions before the study period and/or pre-existing alloantibodies.Cases defined as first time alloantibody formers; Controls defined as transfused individuals matched (on number of transfusions) to cases and have not formed an alloantibody. STATISTICAL ANALYSIS: Logistic regression models will be used to assess the association between the risk to develop antibodies and potential risk factors, adjusted for other risk factors. ETHICS AND DISSEMINATION: Approval at each local ethics regulatory committee will be obtained. Data will be coded for privacy reasons. Patients will be sent a letter and an information brochure explaining the purpose of the study. A consent form in presence of the study coordinator will be signed before the blood taking commences. Investigators will submit progress summary of the study to study sponsor regularly. Investigators will notify the accredited ethics board of the end of the study within a period of 8 weeks.Stemcel biology/Regenerative medicine (incl. bloodtransfusion

Autologous platelet scintigraphy and clinical outcome of splenectomy in immune thrombocytopenia:A systematic review and meta-analysis

Autologous platelet sequestration pattern is associated with post-splenectomy platelet response in patients with immune thrombocytopenia (ITP). However, published results are contradictory, and have not been systematically reviewed. Our aim is to systematically review and meta-analyse the association between sequestration pattern and post-splenectomy platelet response. Articles were selected from MEDLINE when they a) included ITP patients, b) performed scintigraphy, and c) included post-splenectomy platelet response. The 23 included studies (published between 1969-2018) represented 2966 ITP-patients. Response to splenectomy occurred most frequently in patients with a splenic pattern (87.1 % in splenic versus 47.1 % in mixed and 25.5 % in hepatic patterns). A pooled analysis of 8 studies showed an odds ratio of 14.21 (95 % CI: 3.65-55.37) for platelet response in the splenic versus the hepatic group. Our findings indicate that a splenic sequestration pattern is associated with better response after splenectomy. Platelet sequestration patterns may be useful in the clinical decision-making regarding splenectomy.Immunobiology of allogeneic stem cell transplantation and immunotherapy of hematological disease

The role of preoperative iron deficiency in colorectal cancer patients: prevalence and treatment

Background: In preoperative blood management of colorectal cancer patients, intravenous iron therapy is increasingly used to treat anaemia and prevent red blood cell transfusions. However, while iron deficiency is the most common cause of anaemia, little is known about the prevalence and namely type of iron deficiency in this population, whereas both types of iron deficiency (i.e. absolute and functional iron deficiency) are recommended to be treated differently by international cancer guidelines. Objective: The aim of present study is to investigate the prevalence and namely type of iron deficiency in colorectal cancer patients, and to assess its clinical relevance. Methods: Preoperative iron status, clinical parameters (i.e. age, ASA classification, tumour location, tumour stage) and postoperative complications were retrospectively collected for all newly diagnosed colorectal cancer patients in our institution over a 3-year period. Results: Iron deficiency was observed in 163 (48.1%) of 339 patients. Of these iron-deficient patients, 3.7% had an isolated absolute iron deficiency (AID) and 15.3% a functional iron deficiency (FID), while the rest had a combination of AID and FID. Anaemia was present in 66.1% of iron-deficient patients. Iron deficiency was significantly associated with an increased postoperative complication rate (univariable OR 1.94, p = 0.03, multivariable OR 1.84, p = 0.07), with right-sided tumours (p < 0.001), high ASA classification (p = 0.002), advanced tumour stage (p = 0.01) and advanced age (p = 0.04). In comparing clinical parameters between patients with AID and FID, advanced age was significantly associated with FID (p = 0.03), and the presence of anaemia with AID (p = 0.02). Conclusion: In preoperative colorectal cancer patients, there is a high prevalence of iron deficiency, including a high percentage of patients with—a component of—functional iron deficiency, associated with the increased postoperative complication rate. As both types of iron deficiency require a different treatment strategy, our results illustrate the therapeutic potential of especially intravenous iron supplementation in patients with severe iron deficiency and stress the urgency of routinely monitoring preoperative iron status and differentiation between types of iron deficiency. As iron therapy may also be potentially harmful in respect to stimulation of tumour growth, future clinical trials assessing the long-term effect of iron therapy are necessary

Should HLA and HPA-matched platelet transfusions for patients with Glanzmann Thrombasthenia or Bernard-Soulier syndrome be standardized care? A Dutch survey and recommendations

Background: Glanzmann thrombasthenia (GT) and Bernard-Soulier syndrome (BSS) patients require frequent platelet transfusions and hence have an increased risk for alloimmunization against donor Human Leukocyte Antigens (HLA) when no HLA-matching is performed. Knowing that Human Platelet Antigens (HPA) are located on the platelet glycoproteins that can be absent in these patients, preventive HPA-matching may also be considered. Uniform recommendations on this topic lack in transfusion guidelines making standard practice unclear, therefore, we aimed to provide a framework for matched platelet transfusions. Study Design and Methods: We conducted a targeted literature search and a national survey of Dutch (pediatric) hematologists from July to September 2021. Results: We found 20 articles describing platelet transfusion policies in 483 GT-patients and 29 BSS-patients, both adults and children. Twenty surveys were returned for full analysis. All responders treated patients with platelet disorders, including GT (n = 36 reported) and BSS (n = 29 reported). Of respondents, 75% estimated the risk of antibody formation as “likely” for HLA and 65% for HPA. Formation of HLA antibodies was reported in 5 GT and in 5 BSS-patients, including one child. Fifteen respondents gave preventive HLA-matched platelets in elective setting (75%). Three respondents additionally matched for HPA in GT-patients (15%). Main argument for matched platelet transfusions was preventing alloimmunization to safeguard the effectivity of ‘random’ donor-platelets in acute settings. Conclusion: Elective HLA-matching for GT and BSS-patients is already conducted by most Dutch (pediatric) hematologists. HPA-matching is mainly applied when HPA-antibodies are formed. Based on the current literature and the survey, recommendations are proposed.</p

Iron therapy as treatment of anemia: A potentially detrimental and hazardous strategy in colorectal cancer patients

Stemcel biology/Regenerative medicine (incl. bloodtransfusion

Highly Sensitive Flow Cytometry Allows Monitoring of Changes in Circulating Immune Cells in Blood After Tdap Booster Vaccination

© 2021 Diks, Khatri, Oosten, de Mooij, Groenland, Teodosio, Perez-Andres, Orfao, Berbers, Zwaginga, van Dongen and Berkowska.Antigen-specific serum immunoglobulin (Ag-specific Ig) levels are broadly used as correlates of protection. However, in several disease and vaccination models these fail to predict immunity. In these models, in-depth knowledge of cellular processes associated with protective versus poor responses may bring added value. We applied high-throughput multicolor flow cytometry to track over-time changes in circulating immune cells in 10 individuals following pertussis booster vaccination (Tdap, Boostrix®, GlaxoSmithKline). Next, we applied correlation network analysis to extensively investigate how changes in individual cell populations correlate with each other and with Ag-specific Ig levels. We further determined the most informative cell subsets and analysis time points for future studies. Expansion and maturation of total IgG1 plasma cells, which peaked at day 7 post-vaccination, was the most prominent cellular change. Although these cells preceded the increase in Ag-specific serum Ig levels, they did not correlate with the increase of Ig levels. In contrast, strong correlation was observed between Ag-specific IgGs and maximum expansion of total IgG1 and IgA1 memory B cells at days 7 to 28. Changes in circulating T cells were limited, implying the need for a more sensitive approach. Early changes in innate immune cells, i.e. expansion of neutrophils, and expansion and maturation of monocytes up to day 5, most likely reflected their responses to local damage and adjuvant. Here we show that simultaneous monitoring of multiple circulating immune subsets in blood by flow cytometry is feasible. B cells seem to be the best candidates for vaccine monitoring.K is supported by the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 707404. The here presented study is a pilot study for the Innovative Medicines Initiative (IMI) PERISCOPE program, a Joint Undertaking under grant agreement No 115910. This Joint Undertaking receives support from the European Union’s Horizon 2020 Research and Innovation Programme, the European Federation of Pharmaceutical Industries and Associations (EFPIA), and the Bill and Melinda Gates Foundation (BMGF). The flow cytometric studies in this study were supported by the EuroFlow Consortium. The EuroFlow Consortium received support from the FP6-2004-LIFESCIHEALTH-5 program of the European Commission (grant LSHB-CT-2006-018708) as Specific Targeted Research Project (STREP)

Patient blood management in colorectal cancer patients: a survey among Dutch gastroenterologists, surgeons, and anesthesiologists

Stemcel biology/Regenerative medicine (incl. bloodtransfusion

EVALUACIÓN DE RESULTADOS QUIRÚRGICOS DESDE LA PERSPECTIVA DEL PACIENTE

RESUMENMedir la calidad de vida relacionada a salud y los síntomas de los pacientes es un problema difícil. Las medición de los problemas de salud mediante escalas o cuestionarios se ha desarrollado para crear los Instrumentos de Evaluación desde la Perspectiva del Paciente o PRO's por su nombre en inglés: Patient-reported outcomes. Los PROs evalúan la calidad de vida en forma genérica o específica en un continuo, entregando instrumentos que pueden evaluar la gravedad de una enfermedad o el impacto de una intervención desde la perspectiva del paciente en frecuentes escenarios clínicos. El objetivo de la presente revisión es entregar a clínicos e investigadores una introducción hacia los PROs y resumir sus principales propiedades.SUMMARYQuantifying health-related quality of life and specific patient symptoms it is a difficult problem. Health measurement scales has developed to include rigorous techniques to develop patient-reported outcome measures (PROs). PROs assess objectively the QoL in a continuum, providing instruments to measure the severity of a given disease or the impact of a therapeutic intervention from patient perspective in different clinical problems. The following review aims to introduce the PROs to clinicians and researchers and summarize its main properties

Second-line treatment for acute graft-versus-host disease with mesenchymal stromal cells. a decision model

Objective: No standard second-line treatment exists for acute graft-versus-host disease steroid-refractory (SR-aGvHD), and long-term outcomes remain poor. Mesenchymal stromal cells (MSCs) have been evaluated as treatment, but no disease model (DM) exists that integrates and extrapolates currently available evidence. The aim of this study was to develop such a DM to describe the natural history of SR-aGvHD and to predict long-term outcomes. Method: The DM was developed in collaboration with experts in haematology-oncology. Subsequently, a model simulation was run. Input parameters for transition and survival estimates were informed by published data of clinical trials on MSC treatment for SR-aGvHD. Parametric distributions were used to estimate long-term survival rates after MSCs. Results: The newly developed DM is a cohort model that consists of eight health states. For the model simulation, we obtained data on 327 patients from 14 published phase II trials. Due to limited evidence, DM structure was simplified and several assumptions had to be made. Median overall survival was 3.2 years for complete response and 0.5 years for no complete response. Conclusion: The DM provides a comprehensive overview on the second-line treatment pathway for aGvHD and enables long-term predictions that can be used to perform a cost-effectiveness analysis comparing any treatment for SR-aGvHD

Inhibition of dendritic cell activation and modulation of T cell polarization by the platelet secretome

Platelet transfusions are a frequently administered therapy for especially hemato-oncological patients with thrombocytopenia. Next to their primary function in hemostasis, currently there is increased attention for the capacity of platelets to affect the function of various cells of the immune system. Here, we investigate the capacity of platelets to immuno-modulate monocyte-derived dendritic cells (moDC) as well as primary dendritic cells and effects on subsequent T cell responses. Platelets significantly inhibited pro-inflammatory (IL-12, IL-6, TNF alpha) and increased anti-inflammatory (IL-10) cytokine production of moDCs primed with toll-like receptor (TLR)-dependent and TLR-independent stimuli. Transwell assays and ultracentrifugation revealed that a soluble factor secreted by platelets, but not microvesicles, inhibited DC activation. Interestingly, platelet-derived soluble mediators also inhibited cytokine production by human ex vivo stimulated myeloid CD1c+ conventional DC2. Moreover, platelets and platelet-derived soluble mediators inhibited T cell priming and T helper differentiation toward an IFN gamma+ Th1 phenotype by moDCs. Overall, these results show that platelets are able to inhibit the pro-inflammatory properties of DCs, and may even induce an anti-inflammatory DC phenotype, with decreased T cell priming capacity by the DC. The results of this study provide more insight in the potential role of platelets in immune modulation, especially in the context of platelet transfusions.Immunobiology of allogeneic stem cell transplantation and immunotherapy of hematological disease