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Chimeric antigen receptor (CAR) T-cell therapy presents a promising treatment for hematologic malignancies, displaying high efficacy but not being exempt from toxicity. In this observational study, we assessed adverse events (AEs) reported to the Food and Drug Adverse Event Reporting System (FAERS) including any of the six approved CAR T-cell therapies. A total of 5249 reports mentioning a CAR T-cell as a suspect product were retrieved from the FAERS database, containing a total of 24333 AEs, of which 3236 (13.3%) were cytopenias. The highest number of AEs mentioned by the report was observed for tisagenlecleucel (mean = 6.7), with the lowest for ciltacabtagene (mean = 1.3). Among all reports, hematopoietic leukopenia was the most frequently reported AEs ( n  = 1386, 5.7%), with hematopoietic erytropenia the least reported ( n  = 291, 1.2%). Tisagenlecleucel showed a high reporting odds ratio for hematopoietic erythropenia (27.28, 95%CI 14.04-53.00), leukopenia (4.04, 95%CI 3.52-4.64), and thrombocytopenia (4.01, 95%CI 3.19-5.03). Cytopenias represent one of the most frequently reported AEs in FAERS, a CAR T-cell therapy is indicated, with haematopoetic leukopenia being the most common. When comparing different CAR-T cell therapies, the cytopenias' reporting odds ratio was particularly high for tisagenlecleucel, especially in relation to hematopoietic erythropenia .

Background: People who have or had the potential to menstruate (PPM) with inherited bleeding disorders (BD) face particular challenges receiving appropriate diagnosis and care and participating in research. As part of an initiative to create a National Research Blueprint for future decades of research, the National Hemophilia Foundation (NHF) and American Thrombosis and Hemostasis Network conducted extensive all-stakeholder consultations to identify the priorities of PPM with inherited BDs and those who care for them., Research Design and Methods: Working group (WG) 4 of the NHF State of the Science Research Summit distilled community-identified priorities for PPM with inherited BDs into concrete research questions and scored their feasibility, impact, and risk., Results: WG4 identified important gaps in the foundational knowledge upon which to base optimal diagnosis and care for PPM with inherited BDs. They defined 44 top-priority research questions concerning lifespan sex biology, pregnancy and the post-partum context, uterine physiology and bleeding, bone and joint health, health care delivery, and patient-reported outcomes and quality-of-life., Conclusions: The needs of PPM will best be advanced with research designed across the spectrum of sex and gender biology, with methodologies and outcome measures tailored to this population, involving them throughout.

The release of the 2020-2030 Strategic Plan for NIH Nutrition Research (SPNR) and its emphasis on precision nutrition has provided an opportunity to identify future nutrition research that addresses individual variability in response to diet and nutrition across the life span-including those relevant to the Strategic Vision of the National Heart, Lung, and Blood Institute (NHLBI). The SPNR and the NHLBI's Strategic Vision were developed with extensive input from the extramural research community, and both have 4 overarching strategic goals within which are embedded several objectives for research. For the SPNR, these include 1) spur discovery science and normal biological functions (e.g., role of the microbiome in health and disease), 2) population science to understand individual differences (e.g., biomarkers including 'omics that predict disease status), 3) emerging scientific areas of investigation and their application (e.g., data science, artificial intelligence), and 4) cross-cutting themes (e.g., training the scientific workforce and minority health and health disparities). These strategic goals and objectives serve as blueprints for research and training. Nutrition remains important in the prevention and treatment of heart, lung, blood, and sleep (HLBS) disorders and diseases, and the NHLBI has played a pivotal role in supporting nutrition research. In this paper, we report important gaps in the scientific literature related to precision nutrition in HLBS diseases. Research opportunities that could stimulate precision nutrition and their alignment with the SPNR and the NHLBI Strategic Vision Objectives are provided. These opportunities include 1) exploring individual differences in response to varying dietary patterns and nutrients; 2) investigating genetic/epigenetic, biological (e.g., microbiome, biomarkers), social, psychosocial, and environmental underpinnings of individual variability in diet; 3) elucidating the role of circadian rhythm and chrononutrition; and 4) applying implementation science research methods in precision nutrition interventions relevant to HLBS diseases., (Published by Oxford University Press on behalf of the American Society for Nutrition 2022.)

Introduction: Kabuki syndrome is a rare congenital condition characterized clinically by unique facial features, abnormalities in the skeleton, finger pad abnormalities, and developmental delays, as well as a range of other health issues. Existing research lacks information on the daily burden of living with Kabuki syndrome., Methods: A survey collected caregiver- and patient-reported data about the experience of living with Kabuki syndrome in order to better understand its presentation and effect on patients and their psychosocial well-being., Results: A total of 68 participants (n = 57 caregivers and n = 11 adolescents) were recruited from the USA and Canada. Caregiver survey participants reported developmental delays and lower IQ in individuals with Kabuki syndrome compared to the general population, as well as difficulty with cognitive-related tasks, need for educational accommodations, and difficulty with particular school subjects and with daily tasks. Additionally, participants reported significant emotional, social, and communication-related impacts of Kabuki syndrome. Adolescent data largely corroborated the information collected from caregivers, with the exception of adolescents reporting the emotional and social impacts as occurring less frequently., Conclusions: Kabuki syndrome is a multidimensional disease which has substantial negative effects on physical, mental, emotional, and social aspects of health-related quality of life. This research adds to the limited existing body of literature on the clinical presentation of Kabuki syndrome and provides a novel perspective into the caregiver and adolescent perception of the burden of Kabuki syndrome., (© 2021. The Author(s).)

Background: Oncology settings increasingly use patient experience data to evaluate clinical performance. Given that older patients with hematologic malignancies are a high-risk population, this study examined factors associated with patient-reported health care experiences during the first year of their cancer diagnosis., Methods: Cross-sectional study using the 2000-2015 SEER-CAHPS® data to examine patient experiences of Medicare enrollees with a primary diagnosis of leukemia or lymphoma. The primary outcomes were three CAHPS assessments: overall care, personal doctor, and health plan overall. We estimated case-mix adjusted and fully adjusted associations between factors (i.e., clinical and sociodemographic) and the CAHPS outcomes using bivariate statistical tests and multiple linear regression., Results: The final sample included 1,151 patients, with 431 diagnosed with leukemia and 720 diagnosed with lymphoma (median time from diagnosis to survey 6 months). Patients who completed the survey further apart from the diagnosis date reported significantly higher adjusted ratings of care overall (β .39, p = .008) than those closer to diagnosis. American Indian/Alaska Native, Asian, and Pacific Islander patients had lower adjusted ratings of care overall (β - .73, p = .003) than Non-Hispanic white patients. Multimorbidity was significantly associated with higher adjusted personal doctor ratings (β .26, p = .003)., Conclusions: Unfavorable patient experiences among older adults diagnosed with hematologic malignancies warrant targeted efforts to measure and improve care quality. Future measurement of experiences of cancer care soon after diagnosis, coupled with careful sampling of high-priority populations, will inform oncology leaders and clinicians on strategies to improve care for high-risk, high-cost populations.

Objectives: This study examined the association of ED use in the first year of diagnosis and patient experiences in care among older adults with hematologic malignancies., Materials and Methods: Cross-sectional design using SEER-CAHPS® data from 2002 to 2015 to study Medicare fee-for-service enrollees with a primary diagnosis of leukemia or lymphoma. We linked the CAHPS survey data (patient-reported experiences with health services) to patients' cancer registry information and Medicare outpatient claims from the SEER-CAHPS resource. We estimated associations of ED use and clinical characteristics with two CAHPS outcomes - "getting care quickly" (timeliness) and "getting needed care" (access) - with bivariate and multivariate analyses., Results: The analytic sample included 751 patients, 125 of whom had an ED claim in the first year of cancer diagnosis. The most frequent ED diagnosis clusters were fever and infection (n = 17, 13.6%), orthopedic and injury (16, 12.8%) and pain (16, 12.8%). Significantly more enrollees with an ED claim were diagnosed with lymphoma (p < 0.01), lived in rural areas (p < 0.01), and lived in areas with many families living in poverty (p < 0.01). In adjusted models, enrollees with an ED claim reported significantly worse access to care (β - 4.83; 95%CI -9.29,-0.38; p = 0.03)., Conclusion: The management of urgent care concerns for adults with hematologic malignancies remains an important clinical and quality improvement imperative. Further study is warranted to enhance the management of emergent complications in older adults receiving care for hematologic malignancies, with efforts that enhance coordination of ambulatory oncology care., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The novel coronavirus (COVID-19) pandemic has affected all aspects of human life worldwide. Under this situation, the American Society of Hematology and European Hematology Association have provided resources and recommendations for the management of hematologic diseases during the COVID-19 pandemic. This review aims to summarize these recommendations and provide helpful, accurate, and up-to-date information for Japanese hematologists.

Sickle cell disease (SCD) is the most common inherited blood disorder in the United States. It is a medically and socially complex, multisystem illness that affects individuals throughout the lifespan. Given improvements in care, most children with SCD survive into adulthood. However, access to adult sickle cell care is poor in many parts of the United States, resulting in increased acute care utilization, disjointed care delivery, and early mortality for patients. A dearth of nonmalignant hematology providers, the lack of a national SCD registry, and the absence of a centralized infrastructure to facilitate comparative quality assessment compounds these issues. As part of a workshop designed to train health care professionals in the skills necessary to establish clinical centers focused on the management of adults living with SCD, we defined an SCD center, elucidated required elements of a comprehensive adult SCD center, and discussed different models of care. There are also important economic impacts of these centers at an institutional and health system level. As more clinicians are trained in providing adult-focused SCD care, center designation will enhance the ability to undertake quality improvement and compare outcomes between SCD centers. Activities will include an assessment of the clinical effectiveness of expanded access to care, the implementation of SCD guidelines, and the efficacy of newly approved targeted medications. Details of this effort are provided., (© 2020 by The American Society of Hematology.)

Objectives: Non-randomised clinical trial designs involving comparisons against external controls or specific standards can be used to support regulatory submissions for indications in diseases that are rare, with high unmet need, without approved therapies and/or where placebo is considered unethical. The objective of this review was to summarise the characteristics of non-randomised trials submitted to the European Medicines Agency (EMA) or Food and Drug Administration (FDA) for indications in haematological cancers, haematological non-malignant conditions, stem cell transplants or rare metabolic diseases., Methods: We conducted systematic searches of EMA databases of conditional approvals, exceptional circumstances, or orphan drug designations and FDA inventories of orphan drug designations, accelerated approvals, breakthrough therapy, fast-track and priority approvals. Products were included if reviewed by at least one agency between 2005 and 2017, the primary evidence base was non-randomised trial(s) and the indication was for haematological cancers, stem cell transplantation, haematological conditions or rare metabolic conditions., Results: We identified 43 eligible indication-specific products using non-randomised study designs involving comparisons with external controls, submitted to the EMA (n=34) and/or FDA (n=41). Of the 43 indication-specific products, 4 involved matching external controls to the population of a non-randomised interventional study using individual patient-level data (IPD), 12 referred to external controls without IPD and 27 did not explicitly reference external controls. The FDA approved 98% of submissions, with 56% accelerated approvals; most required postapproval confirmatory randomised controlled trials (RCT). The EMA approved 79% of submissions, with a quarter of approvals conditional on completion of a postapproval RCT or additional non-randomised trials., Conclusions: There has been a large increase in submissions to the EMA and FDA using non-randomised study designs involving comparisons with external controls in recent years. This study demonstrated that regulators may be willing to approve such submissions, although approvals are often conditional on further confirmatory evidence from postapproval studies., Competing Interests: Competing interests: AT is an employee of Takeda. EEK, TJJL and KM are employees of ICON, a CRO that was paid by Takeda to perform this study and to draft this manuscript. SG was an employee and is a consultant for ICON. ARL is a consultant for ICON. NF has received funding for research, travel or consultation from Sanofi Aventis, Takeda, Allegan, Biopharma, Ipsen, Servier, Pfizer and Novo Nordisk., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The National Heart, Lung, and Blood Institute (NHLBI) provides global leadership for a research, training, and education program to promote the prevention and treatment of heart, lung, and blood diseases and enhance the health of all individuals so that they can live longer and more fulfilling lives. Inherent in this mission is the commitment to advance health equity research as an avenue for enhancing the health of all individuals. Additionally, the four goals and eight research objectives of the NHLBI Strategic Vision directly support the commitment to health equity. In this article, we present selected examples of the NHLBI Strategic Vision implementation approaches for advancing health equity research in our mission areas of heart, lung, and blood diseases. Examples of diseases for which the burden of health inequities and our strategic vision implementation approaches are discussed include hypertension, heart failure, vascular dementia, asthma, and sickle cell disease. Examples are provided of new avenues of Institute-solicited research to stimulate and address compelling scientific questions and critical challenges to advance health equity. We also highlight the emerging fields of implementation science and predictive analytics as important opportunities to accelerate the translation of discovery science into health impact for all and to advance health equity., Competing Interests: Competing Interests: None declared.

We are extending the expiration dates of the following body systems in the Listing of Impairments (listings) in our regulations: Genitourinary Impairments and Hematological Disorders. We are making no other revisions to these body systems in this final rule. These extensions will ensure that we continue to have the criteria we need to evaluate impairments in the affected body systems at step three of the sequential evaluation processes for initial claims and continuing disability reviews.

Background: Post donation information (PDI) is the most frequently reported biological product deviation (BPD) related to donor suitability and the health history screening process. PDI occurs when a deferrable health history known by the donor is not disclosed, but is subsequently disclosed at a future donation., Study Design and Methods: PDI and appropriately deferred (AD) donors were identified at six US blood centers from July 1, 2006, to June 30, 2007. PDI and AD donors were categorized according to travel, medical, blood disease or exposure, and high-risk-sexual and high-risk-nonsexual deferrals. Information was obtained from BPD reports and blood center records. Predictors of PDI were identified using an adjusted logistic regression model controlling for select characteristics., Results: There were 2059 PDI and 36,512 AD donors. PDI donors were significantly more likely to be male, older, and more educated than AD donors. Medical and high-risk-sexual PDI donors were more likely to have more than six intervening donations before disclosure of deferrable history. PDI donors with a deferral reason due to high-risk behaviors (both sexual and nonsexual) were 2.3 and 2.6 times more likely to be PDI than the reference group (travel PDI donors)., Conclusions: No previous studies have described the characteristics of PDI donors or examined how PDI donors are different from AD donors for the same deferral reasons. We found that PDIs are more likely in older, male donors with higher levels of education when compared to AD donors., (© 2011 American Association of Blood Banks.)

We are extending the expiration dates of the following body systems in the Listing of Impairments (listings) in our regulations: Cardiovascular System, Endocrine System, Growth Impairment, Hematological Disorders, Musculoskeletal System, Mental Disorders, Neurological, and Respiratory System. We are making no other revisions to these body system listings. This extension will ensure that we continue to have in the listings the criteria we need to evaluate impairments in the affected body systems at the appropriate steps of the sequential evaluation processes for initial claims and continuing disability reviews.

The interest of young MDs and PhDs in research careers was assessed by determining the number of former trainees who applied for and (or) received research support from the Public Health Service. Thirty-two percent of trainees supported by Institutional Training Grants between 1977 and 1981 made a subsequent application. Seventy-six percent of all those who submitted applications to the National Institutes of Health (NIH) for research project support received awards. Examination of the success rate for individual applications submitted by former trainees showed that 56% of all applications submitted by MD scientists were awarded, and 57% of all applications submitted by PhD scientists were awarded. This compares to an NIH-wide average of 33.3% for the same period. The number of appointments made to Institutional Training Grants for a full year remained fairly constant over a 6-year period, as did the number appointed to individual fellowships over an 8-year period. The dollars expended on Institutional Training Grants increased 33% from 1982 to 1986 for a similar number of trainees, and increased 30% from 1981 to 1988 for a similar number of individual fellowships. The number of Research Career Development Award (RCDA) applications declined by 66% for MDs and by 53% for PhDs, accounting for a 32% reduction in the number of active RCDAs held by MDs and a 60% reduction in active RCDAs held by PhDs from 1985 to 1988. MD scientists submitted more applications, had higher award rates, and received more RCDA awards than did PhD scientists.(ABSTRACT TRUNCATED AT 250 WORDS)