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BackgroundAt the start of the coronavirus disease 2019 (COVID-19) pandemic, widespread blood shortages were anticipated. We sought to determine how hospital blood supply and blood utilization were affected by the first wave of COVID-19.Study design and methodsWeekly red blood cell (RBC) and platelet (PLT) inventory, transfusion, and outdate data were collected from 13 institutions in the United States, Brazil, Canada, and Denmark from March 1st to December 31st of 2020 and 2019. Data from the sites were aligned based on each site's local first peak of COVID-19 cases, and data from 2020 (pandemic year) were compared with data from the corresponding period in 2019 (pre-pandemic baseline).ResultsRBC inventories were 3% lower in 2020 than in 2019 (680 vs. 704, p

Background: The success of allogeneic hematopoietic stem cell transplantation is dependent on a world‐wide network of collection centers providing donations that predominantly have been infused as fresh cells. The logistics chain that supports the just‐in‐time delivery model for stem cell and immunotherapy products was severely stressed by the COVID pandemic, and in early 2020 a number of national and international bodies recommended that cells should be cryopreserved at the collection or transplant center to avoid interruptions in their acquisition or delivery to patients who had started conditioning. Study Design: To assess the potential consequences of such pandemic‐related deviations to normal practice, we surveyed nine international laboratories to determine if the characteristics or transplant outcomes of allogeneic stem cell donations differed in the immediate periods before and after the switch to routine cryopreservation. Results: Nine centers on two continents provided data for 72 HSC donations just before, and 71 just after, switching to cryopreservation for allogeneic HSC products. No statistically significant differences between the period before and after cryopreservation were noted for time from product collection to receipt, product temperature at receipt, or CD34+ cell viability at receipt. There was an indication of slower absolute neutrophil count recovery after cryopreservation was required (mean time of 15 vs. 17.6 days). Discussion: While there were no apparent changes to most parameters studied, there was an indication of slower neutrophil engraftment that will need to be examined in larger, longer term studies. [ABSTRACT FROM AUTHOR]

Background: Chimeric antigen receptor T (CAR‐T) cell successes have encouraged continued clinical study. Apheresis collection of starting material for CAR‐T cell therapy product manufacturing is critical but described approaches suggest variability and clinical guidelines are currently lacking. The goal of this study was to gather and assess variability in apheresis collection descriptions in publicly available CAR T‐cell therapy clinical trials. Study design: We searched clinicaltrials.gov (a publicly available clinical trial database) for "chimeric antigen receptor T cells" on July 01, 2020 and studies accessed July 30, 2020‐August 15, 2020. Data collected included date posted, study characteristics, apheresis mentions (number, location, and context), laboratory parameters and transfusion allowances. Apheresis context was analyzed using a qualitative inductive approach of grounded theory method with open coding. Text was classified into 37 context codes, grouped into 12 categories, and then consolidated into patient, procedure, product, and miscellaneous themes. Results: Apheresis was mentioned 1044 times in 322 (51.9%) of 621 total studies. Laboratory parameters mentioned included white blood cells (100 studies), absolute neutrophil count (220 studies), absolute lymphocyte count (102 studies), CD3+ cell (38 studies), hemoglobin (233 studies, 54 studies specified transfusion allowance), and platelet (269 studies, 48 studies specified transfusion allowance). Conclusions: Apheresis collection of CAR‐T cell products is not well‐defined in clinical study descriptions and the context is inconsistent. Laboratory parameters useful for apheresis collection are variably present and do not consistently align with current practices. Further exploration, and clinical guideline development will encourage alignment of apheresis collections for CAR‐T cell products. [ABSTRACT FROM AUTHOR]

Background: Growth in size and complexity of clinical hematopoietic progenitor cell (HPC) transplant programs necessitates parallel increases in cellular therapy laboratory (CTL) workload. Typically individually developed, HPC product processing is labor and time intensive. Variation in procedure type and numbers across CTLs complicates direct comparisons, and benchmark data are not readily available.Study Design and Methods: Studies were undertaken at seven CTLs. Transplant volume and staff numbers were determined. Staff recorded time performing tasks broken down into steps: paperwork, product acceptance, transport/infusion, processing, and cryopreservation. Times were added to obtain total times for 15 common CTL procedures.Results: Annual transplant volume ranged from 53.4 to 463.2, with products processed by a range of 2 to 10 dedicated CTL staff. Paperwork time constituted 23.7% to 62.3% total time; product processing time accounted for 1.8 (for National Marrow Donor Program product receipt) to 62.6% (for red blood cell reduction of allogeneic HPC products from bone marrow) of total processing time. Mean time for 15 procedures ranged from 1.27 to 8.28 hours (standard deviation range, 0.35-2.71 hr). Mean time for products from bone marrow versus peripheral blood was 6.6 ± 2.0 versus 5.5 ± 1.1 hours (p = 0.02). Cryopreservation (6.5 ± 1.6 vs. 4.4 ± 0.85 hr; p < 0.01) and manipulation (6.4 ± 1.5 vs. 4.4 ± 0.85 hr; p < 0.01) added time.Conclusion: CTL procedures are time intensive, with wide intra- and inter-CTL variation. Paperwork accounted for substantial portion of total time across procedures. Bone marrow source, cryopreservation, and manipulation contributed to longer times. These findings provide concrete data on which to build regarding CTL workload capacity. [ABSTRACT FROM AUTHOR]

Background: Therapeutic plasma exchange (TPE) utilizes an extracorporeal circuit to remove pathologic proteins causing serious illness. When processing a patient's entire blood volume through an extracorporeal circuit, proteins responsible for maintaining hemostatic system homeostasis can reach critically low levels if replacement fluid types and volumes are not carefully titrated, which may increase complications. Methods: The charts from 27 patients undergoing 46 TPE procedures were reviewed to evaluate the accuracy of our predictive mathematical model, utilizing the following patient information: weight, hematocrit, pre‐ and post‐TPE factor levels (fibrinogen, n = 46, and antithrombin, n = 23), process volume and volumes of fluids (eg, plasma, albumin, and normal saline) administered during TPE and adverse events during and after TPE. Results: Altogether, 25% of patients experienced minor adverse events that resolved spontaneously or with management. There were no bleeding or thrombotic complications. The mean difference between predicted and measured post‐TPE fibrinogen concentrations was −0.29 mg/dL (SD ±23.0, range −59 to 37), while percent difference between measured and predicted fibrinogen concentration was 0.94% (SD ±10.8, range of −22 to 19). The mean difference between predicted and measured post‐TPE antithrombin concentrations were 0.89% activity (SD ±10.0, range −23 to 14), while mean percent difference between predicted and measured antithrombin concentrations was 3.87% (SD ±14.5, range −25 to 38). Conclusions: Our model reliably predicts post‐TPE fibrinogen and antithrombin concentrations, and may help optimize patient management and attenuate complications. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor (CAR)‐T cells have proven to be an effective cancer therapy for CD19‐expressing neoplasms. Efforts to optimize the manufacturing process can help to ensure the efficacy and safety of the therapy. Peripheral blood T cells, which serve as the source material, are collected by apheresis. However, the majority of apheresis collection protocols do not selectively collect T cells, but rather isolate the mononuclear cell (MNC) layer, which also contains other mononuclear leukocytes present in the peripheral blood. Since currently CAR‐T cells are autologous, the patient's clinical condition is a major factor in the planning, coordination, and execution of the apheresis procedure to subsequently manufacture the product successfully. Efforts have been made to identify predictors of a successful collection (ie, precollection peripheral blood CD3+ count). The characteristics of the source material influences the manufacturing process directly, and therefore affects the quantity, viability, immune cell composition, and T cell phenotypic makeup of the final product. Here we review the CAR‐T cell manufacturing process from the apheresis perspective, highlighting considerations before, during, and after collection that could potentially alter the outcome of the manufacturing process and ultimately, the safety and efficacy of the therapy for the patient. [ABSTRACT FROM AUTHOR]

Abstract: Cytotoxic T cells (CTLs) are an important component of adaptive immunity. The study of antigen-specific CTLs in vivo is desirable yet difficult. Identification of the class I-restricted peptide used by CTLs for target recognition is often required for detailed studies, but is generally not known for most antigens. Toxoplasma gondii is a medically important, obligate intracellular parasite and is often used as a model for studies of parasite immunology. No class I-restricted peptides for CTLs are known. We show here a new and convenient method to detect T. gondii-specific CTLs in vivo. We engineered T. gondii tachyzoites to express the model antigen ovalbumin, for which many useful reagents and transgenic mice are available. Using ovalbumin-transgenic T. gondii tachyzoites, antigen-specific CTLs were detected in vivo, and at much earlier time points post-infection than previously reported. This new method has several additional advantages over current methods to detect T. gondii-specific CTLs. [Copyright &y& Elsevier]

Advances in HIV drug therapy have drastically decreased mortality and significantly improved quality of life for HIV infected patients since the early days of the epidemic. However, HIV drug-resistance, drug toxicities, therapy adherence, and the need for life-long treatment remain major challenges that continue to contribute to HIV-related global health concerns. Recent advances in cancer immunotherapy have proven the potency of cellular gene therapies. An ever-growing toolbox of methods of gene manipulation, cell modification, and clinical cell manufacturing, will enable moving beyond continuous drug therapy for more effective and durable treatments, including the possibility of inducing permanent resistance to HIV. These approaches, which target both host and viral factors, capitalize on points of vulnerability in the virus life cycle. Cellular and gene therapy has the potential to be an effective one-time therapy with less toxicity. Here, we review several promising strategies currently in pre-clinical development and clinical trials.