[CHIMERIC ANTIGEN RECEPTOR T CELLS (CAR-T CELLS) THERAPY FOR B-CELL HEMATOLOGICAL MALIGNANCIES - FROM THE ISRAELI SOCIETY OF HEMATOLOGY AND TRANSFUSION MEDICINE].

INTRODUCTION: Using immunotherapy to fight cancer, and specifically, the use of engineered T-cells expressing a chimeric receptor against an antigen found on malignant cells (chimeric antigen receptor, CAR-T cells) constitutes a significant breakthrough in the treatment of the disease. In recent years, several CAR-T therapies have been approved in Europe and the USA, and some are already approved and funded through the national health basket in Israel, for the indications of diffuse large B-cell lymphoma, mantle cell lymphoma and B-cell acute lymphoblastic leukemia, after the failure of at least two lines of treatment. The treatment with CAR-T cells achieves prolonged remissions and even long-term cure of patients who had a very poor prognosis. However, the treatment involves significant side effects, and requires specific expertise in the management of patients both during the period of preparation for cell transplantation, and following the treatment. During the immediate post-infusion period, the most common adverse reactions are cytokine release syndrome (CRS) which stems from the activation of the immune system, and neurological toxicity that can accompany CRS. These effects require close monitoring, grading their severity, and providing anti-cytokine therapy or steroid therapy until control of symptoms is achieved. Later effects can be persistent cytopenias, immune over-activation, and prolonged immune deficiency. Treatments for additional indications and new CAR-T constructs are being developed and will allow more effective and safer treatment. This article summarizes the principles for CAR-T administration that, as currently provided in Israel, include the short- and long-term follow-up of the patients.

Advancing in vivo assessment of red blood cell transfusions: A call for radiation-free methods in transfusion medicine.

RBC transfusions are a vital clinical therapy to treat anemic patients. The in vivo assessment of red blood cell (RBC) quality post-transfusion is critical to ensuring that the introduction of new RBC products meet established regulatory and clinical quality requirements. Although in vitro quality control testing is routinely performed by blood manufacturers, it is crucial that in vivo tests are performed during the evaluation and regulatory process of new RBC products. This article reviews existing in vivo techniques, like chromium-51 labelling and biotinylation, for determining the circulation and survival of RBCs, and advocates for a move to radiation-free methods. The timely need for radiation-free methods to assess emerging non-DEHP container systems is just one example of why efforts to improve the methods available for in vivo quality assessment is important in transfusion medicine. This review aims to advance our understanding of RBC transfusion in vivo quality assessment and enhance transfusion practices.

Gender differences in scholarly productivity of early-career transfusion medicine physicians.

BACKGROUND AND OBJECTIVES: Promotion in academic medicine requires evidence of the creation and dissemination of scholarly output, primarily through peer-reviewed publications. Studies demonstrate that scholarly activity and impact are lower for women physicians than for men physicians, especially during the early stages of their academic careers. This report reviewed physicians' academic productivity after passing their Blood Banking/Transfusion Medicine (BBTM) subspecialty exam to determine if gender discrepancies exist. METHODS: A cross-sectional analysis was designed to determine trends in scholarly activity for women physicians versus men physicians in BBTM. Indexed publications were reviewed using iCite, the National Institutes of Health (NIH) Office of Portfolio Analysis tool, from 1 January 2017 to 1 December 2021, for BBTM examinees who passed the sub-speciality fellowship exam in the years 2016 through 2018. RESULTS: Overall, women physicians had statistically significant fewer total career publications (median 6 vs. 9 cumulative papers, p = 0.03). Women published at a lower rate after passing BBTM boards, which was not statistically significant (0.7 vs. 1.3 publications per year). Other statistically significant findings include fewer early-career BBTM women physicians were first authors compared with men physicians (p = 0.03) and impact as assessed by relative citation ratio was higher for men (p = 0.01). CONCLUSIONS: This study demonstrates that there are gender differences in scholarly productivity and impact on early-career BBTM physicians. Given that this cohort of BBTM physicians are early-career professionals, the significant difference in first authorship publications between women and men physicians is especially concerning. Publication metrics should be followed to ensure equitable research environments for early-career BBTM physicians.

The effect of serious game and problem-based learning on nursing students' knowledge and clinical decision-making skill regarding the application of transfusion medicine in pediatric nursing.

PURPOSE: Comparing the effect of serious game and problem-based learning on nursing students' knowledge and clinical decision-making skill regarding the application of transfusion medicine in pediatric nursing. DESIGN AND METHODS: In this quasi-experimental study, 76 undergraduate nursing students were enrolled through a convenience sampling method, and were allocated to one of the three groups of serious game, problem-based learning, and control through the block randomization method. Data were collected using a valid and reliable 3-part researcher-made tool, completed before and two weeks after the intervention. Statistical analysis was performed using paired t-test, analysis of covariance, and Bonferroni post hoc test. A significance level of <0.05 was considered. RESULTS: After the intervention, mean scores of both knowledge and clinical decision-making skill increased significantly in both intervention groups (p < 0.05). Mean post-test scores of both knowledge and clinical decision-making skill in the serious game group, and only clinical decision-making skill in the problem-based learning group were significantly higher than the control group (p < 0.05). However, no significant difference was observed regarding mean post-test scores of both knowledge and clinical decision-making skill between the intervention groups (p > 0.05). CONCLUSIONS: Both serious game and problem-based learning are proven to be effective in improving nursing students' knowledge and clinical decision-making skill regarding the application of transfusion medicine in pediatric nursing. PRACTICE IMPLICATIONS: Since learning now occurs beyond classrooms and the new generation of students spend most of their time in virtual places, utilizing technology-based teaching methods like serious games can benefit both educators and students by providing continuous education, saving their time and expenses, etc.

Has the knowledge economy a role to play in transfusion medicine?

The history of blood transfusion has been dominated by the search for compatibility for species specificity, the search for how to transfer blood from one individual into another or infuse. Safety has become a major issue since it became clear that blood was not only able to allow mystical miracles to take place but could transmit infectious diseases. The science behind these ideas reflects observation, a thinking and exchange of knowledge and skills, originally documented in reports or case studies of what has happened and was observed, and peer presented - knowledge economy.

Spotlights on the trends in performance assessment of qualitative in vitro diagnostic medical devices in transfusion medicine.

For reliable clinical decisions in transfusion medicine, assessing the performance of qualitative tests performed in medical laboratories is critical. When false results are reported, these can lead to an adverse reaction to blood components. Good performance assessment practices are essential for this kind of scenario, and they still remain as one of the many unmet high-priority challenges in this area. This paper aims to provide an overview of the current trends in this field. A review of the IFCC-IUPC. qualitative vocabulary was carried out, and a particular focus was given to the evaluation protocols CLSI EP12-A3 and Eurachem AQA, such as the European Union Regulation for class D in vitro diagnostic medical devices. There is a consistency between the current protocols and recognized performance assessment principles, which are mandatory in transfusion service labs. We believe that a revised imprecision interval approach and models based on emerging qualitative test types may prove beneficial in the long run. It is also important to emphasize the uncertainty of proportions to mitigate the risk of misclassification.

Insights on trends in the management of metrological analysis of devices in blood and transfusion medicine services: Verification based on their fitness for purpose and suitability for their respective applications.

In the field of blood and transfusion medicine, European Directorate for the Quality of Medicines & HealthCare recommends practices for metrological devices. Monitoring and measurement resources, as well as their permitted metrological limits, must be considered in this regard. We must understand variables such as metrological domains, the International System of Units, metrological traceability, and metrological requirements and controls in the field of transfusions in order to understand these metrological devices. An approach to metrological analysis and subsequent actions was constructed using flowcharts. As part of this methodology, a metrological device was selected, along with regulatory and normative requirements. A calibration and a test were conducted to demonstrate the application of the figure based on current recommendations. Current recommendations are consistent with the suggested ROC approach. The metrological devices must be verified based on their suitability for their respective applications (fitness-for-purpose).

The role and importance of epidemiology in transfusion medicine.

Transfusion therapy is an indispensable form of treatment, and an important element of the public health system. Due to its origin, blood's clinical use is associated with various risks that may cause adverse reactions and events. Progress in quality and safety of blood components has eliminated numerous risks, especially those of infectious origin. However, some risks cannot be predicted, while others cannot always be prevented. Globalisation and climate change constantly favour the spread of infectious agents. Against this, epidemiology plays a central role in ensuring the safety of transfusion treatment, by continuous surveillance and timely identification of risks, and in the development of routine and additional tests as measures for risk mitigation. As a quantitative discipline based on research methods, epidemiology is a method of reasoning; it relies on the generation and testing of hypotheses; it utilises other scientific resources, particularly in the field of blood donation and blood transfusion, thus having many applications. The main focus falls on transfusion-transmissible infections, and on environmental or occupational diseases, injuries, disabilities and death causes at large. The practice of epidemiology relies on a systematic approach and measurement of disease frequencies. Surveillance is a key element, involving continuously gathering, analysing, and evaluating data regarding diseases, morbidity and mortality, and disseminating the conclusions of the analyses to relevant competent authorities; in this way, action is taken for disease prevention and control. Surveillance systems also provide an important tool for risk assessment, a method to assess and characterise the critical parameters in the functionality of equipment, systems or processes of using scientific data in order to estimate the magnitude of any health effect that derives from decisions of policy makers. Epidemiological surveillance, particularly for the incidence of adverse reactions and adverse events associated with blood transfusion at the national and international levels, has demonstrated the importance of multidisciplinary cooperation between blood and public health services.

Next Generation Sequencing of Red Blood Cell Antigens in Transfusion Medicine: Systematic Review and Meta-Analysis.

Molecular analysis of blood groups is important in transfusion medicine, allowing the prediction of red blood cell (RBC) antigens. Many blood banks use single nucleotide variant (SNV) based methods for blood group analysis. While this is a well-established approach, it is limited to the polymorphisms included in genotyping panels. Thus, variants that alter antigenic expression may be ignored, resulting in incorrect prediction of phenotypes. The popularization of next-generation sequencing (NGS) has led to its application in transfusion medicine, including for RBC antigens determination. The present review/meta-analysis aimed to evaluate the applicability of the NGS for the prediction of RBC antigens. A systematic review was conducted following a comprehensive literature search in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Studies were selected based on predefined criteria and evaluated using Strengthening the Reporting of Observational studies in Epidemiology guidelines. The characteristics and results of the studies were extracted and meta-analysis was performed to verify the agreement between results from standard molecular methods and NGS. Kell (rs8176058), Duffy (rs2814778, rs12078), or Kidd (rs1085396) alleles were selected as a model for comparisons. Additionally, results are presented for other blood group systems. Of the 864 eligible studies identified, 10 met the inclusion criteria and were selected for meta-analysis. The pooled concordance proportion for NGS compared to other methods ranged from 0.982 to 0.994. The sequencing depth coverage was identified as crucial parameters for the reliability of the results. Some studies reported difficulty in analyzing more complex systems, such as Rh and MNS, requiring the adoption of specific strategies. NGS is a technology capable of predicting blood group phenotypes and has many strengths such as the possibility of simultaneously analyzing hundred individuals and gene regions, and the ability to provide comprehensive genetic analysis, which is useful in the description of new alleles and a better understanding of the genetic basis of blood groups. The implementation of NGS in the routine of blood banks depends on several factors such as cost reduction, the availability of widely validated panels, the establishment of clear quality parameters and access to bioinformatics analysis tools that are easy to access and operate.

How do we design a laboratory space for a hospital transfusion medicine service?

BACKGROUND: Transfusion service laboratories (TSL) often need to renovate or design new laboratory space, and their leaders must be involved in the complex and multifaceted design process. STUDY DESIGN AND METHODS: This manuscript outlines the design process and considerations for a dedicated TSL space. RESULTS: Proactive engagement with key collaborators throughout the design process is essential. Major design considerations include physical features such as location, size, service/equipment needs, and zones within the laboratory; intangible issues such as efficiency, well-being, and disaster planning; and adaptations for suboptimal space and changes over time. CONCLUSION: Investing in the design of the laboratory space facilitates high-quality TSL operations, productivity, customer satisfaction, regulatory compliance, staff well-being, and most importantly, patient safety.

Connectivity in transfusion medicine: Challenges, benefits, and goals.

Transfusion medicine requires meticulous record keeping from the time a blood donation is made to the time a patient receives a transfusion. As such, blood collection establishments and processing laboratories generate large amounts of data. This data must be managed, analyzed, and visualized appropriately to ensure safety of the blood supply. Today, the use of information technology (IT) solutions for data management in transfusion medicine varies widely between institutions. In this report, blood center professionals describe how they currently use IT solutions to improve their blood processing methods, the challenges they have, and how they envision IT solutions improving transfusion medicine in the future.

Trends in Gender of Authors of Patient Blood Management Publications.

BACKGROUND: Diverse representation in the field of patient blood management (PBM) may help bring varying perspectives to improve patient care. We assessed trends in gender of first and last authorship of recent PBM publications to evaluate diversity within the field. METHODS: Publications from 10 high-impact anesthesiology and blood transfusion medicine journals between 2017 and 2021 were reviewed using 19 keywords to identify PBM-related articles. Each publication title was reviewed independently to determine whether it met the inclusion criteria. A software program was used to identify the gender of each first and last author for the most common first names. Author gender that could not be identified through this process was determined by querying institutional websites and professional social networks (eg, ResearchGate). Any publication where the gender of the first and/or last author could not be reliably determined was excluded from the analysis. Trends over time were assessed using the Cochran-Armitage test. RESULTS: A total of 2467 publications met the inclusion criteria of the 2873 yielded by the initial search. Gender of the first and last author was identified for 2384 of these publications and included in the final analysis. Approximately 42.8% of publications featured a woman as the first author with the highest from the journals such as the Journal of the American Medical Association ( JAMA ) (48.7%) and Transfusion (48.1%) and the lowest from the journals such as the British Journal of Anaesthesia (24.1%) and Anesthesia & Analgesia (24.4%). Approximately 32.0% of the publications featured a woman as the last author with the highest being Transfusion (36.9%) and Anaesthesia (31.8%) and the lowest being Anesthesia and Analgesia (18.3%) and Anesthesiology (18.6%). Approximately 57.6% of publications had either a woman as the first or last author while 16.3% of the publications had women as both the first and last authors. Women authors comprised 32.6% of the publications with a single author. Women as the first or last authors did not change significantly over the study period ( P = .115 and P = .119, respectively). No significant difference was observed in the percentage of PBM articles with a woman as the first or last author, a woman as the first and last author, or a woman as a single author from 2017 to 2021 ( P = .089, P = .055, and P = .226, respectively). CONCLUSIONS: The percentage of women as the first and last authors in PBM publications from the 5-year period of 2017 to 2021 was <50%. Gender equity in PBM authorship was identified as an area for potential future improvement. International mentorship and sponsorship of women remain important in promoting gender equity in PBM authorship.

Involvement of Diverse Populations in Transfusion Medicine Research.

Communities of color and diverse communities (eg, race, socioeconomic status, language, sexual orientation etc.) have not been recruited and enrolled equitably to participate in research studies in transfusion medicine. The exclusion of diverse communities in transfusion research can lead to health disparities lack of access to approved therapeutics and unequal allocation of interventions, resulting in missed opportunities to optimize health for individuals and communities. Involvement of diverse populations in research goes beyond inclusion as research subjects. Strategies should include specific studies on health conditions of importance to diverse communities with stable funding sources and specific funding announcements to develop projects led by diverse researchers, mentorship of diverse researchers, and openness to various ways of communicating research plans. Qualitative approaches and interdisciplinary collaboration should be supported to enhance inclusivity.