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Background: Most chimeric antigen receptor T (CAR-T) cells and other adoptive T-cell therapies (ACTs) are currently manufactured by ex vivo expansion of patient lymphocytes in culture media supplemented with human plasma from group AB donors. As lymphocytes do not express A or B antigens, the isoagglutinins of non-AB plasmas are unlikely to cause deleterious effects on lymphocytes in culture.Study Design and Methods: Seeding cultures with peripheral blood mononuclear cell (PBMNC) concentrates from group A1 donors and using a CAR-T culture protocol, parallel cultures were performed, each with unique donor plasmas as media supplements (including group O plasmas with high-titer anti-A and group AB plasmas as control). An additional variable, a 3% group A1 red blood cell (RBC) spike, was added to simulate a RBC-contaminated PBMNC collection. Cultures were monitored by cell count, viability, flow cytometric phenotype, gene expression analysis, and supernatant chemokine analysis.Results: There was no difference in lymphocyte expansion or phenotype when cultured with AB plasma or O plasma with high-titer anti-A. Compared to controls, the presence of contaminating RBCs in lymphocyte culture led to poor lymphocyte expansion and a less desirable phenotype-irrespective of the isoagglutinin titer of the plasma supplement used.Conclusions: This study suggests that ABO incompatible plasma may be used as a media supplement when culturing cell types that do not express ABO antigens-such as lymphocytes for CAR-T or other ACT. The presence of contaminating RBCs in culture was disadvantageous independent of isoagglutinin titer. [ABSTRACT FROM AUTHOR]

Multiple hematopoietic progenitor cell (HPC) transplantation options for patients with sickle cell disease (SCD) are currently under investigation. Patients with SCD have a high rate of alloimmunization to red blood cell antigens, often complicating transfusion support. Transfusion reactions, including acute and delayed hemolytic reactions, have been observed despite immunosuppressive regimens. Allogeneic donor transplants have been shown to carry a risk of prolonged reticulocytopenia and acute hemolysis with severe anemia in nonmyeloablative regimens. We discuss our experience providing transfusion support to patients with SCD undergoing HPC transplantation, propose an outline for a complete pretransplantation evaluation, and discuss donor/recipient compatibility issues and their implications. [ABSTRACT FROM AUTHOR]

Objectives: While critical value procedures have been adopted in most areas of the clinical laboratory, their use in transfusion medicine has not been reviewed in detail. The results of this study present a comprehensive overview of critical value reporting and communication practices in transfusion medicine in the United States.Methods: A web-based survey was developed to collect data on the prevalence of critical value procedures and practices of communicating results. The survey was distributed via email to US hospital-based blood banks.Results: Of 123 facilities surveyed, 84 (68.3%) blood banks had a critical value procedure. From a panel of 23 common blood bank results, nine results were selected by more than 70% of facilities as either a critical value or requiring rapid communication as defined by an alternate procedure.Conclusions: There was overlap among results communicated by facilities with and without a critical value procedure. The most frequently communicated results, such as incompatible crossmatch for RBC units issued uncrossmatched, delay in finding compatible blood due to a clinically significant antibody, and transfusion reaction evaluation suggestive of a serious adverse event, addressed scenarios associated with the leading reported causes of transfusion-related fatalities. [ABSTRACT FROM AUTHOR]

The test aliquot and subsequent transplanted HPC-A aliquots thawed without issue, meeting all quality control parameters. A 73-year-old male with IgG-lambda multiple myeloma, treated with Bortezomib, Dexamethasone, and Revlimid, presented after mobilization with Filgrastim to donate hematopoietic progenitor cells by apheresis (HPC-A) in preparation for autologous stem cell transplantation.1,2 The patient's baseline coagulation tests, serum protein electrophoresis, and quantitative immunoglobulin panel were unremarkable. [Extracted from the article]

Abstract: Chagasic cardiomyopathy caused by Trypanosoma cruzi is a major health concern in Latin America and among immigrant populations in non-endemic areas. T. cruzi has a high affinity for host lipoproteins and uses the low density lipoprotein receptor (LDLr) for invasion. Herein, we report that T. cruzi infection is associated with an accumulation of LDL and cholesterol in tissues in both acute and chronic murine Chagas disease. Similar findings were observed in tissue samples from a human case of Chagasic cardiomyopathy. T. cruzi infection of cultured cells displayed increased invasion with increasing cholesterol levels in the medium. Studies of infected host cells demonstrated alterations in their cholesterol regulation. T. cruzi invasion/infection via LDLr appears to be involved in changes in intracellular cholesterol homeostasis. The observed changes in intracellular lipids and associated oxidative stress due to these elevated lipids may contribute to the development of Chagasic cardiomyopathy. [Copyright &y& Elsevier]

A case study is presented of a 36-year-old woman with relapsed leukemia and severe neutropenia. She received acetaminophen and diphenhydramine, with one single-donor platelet unit followed by a red blood cell (RBC); after second unit of RBC patient developed rigors with temperature, tachycardia, and hypotension, further delayed presentation of septic transfusion reaction incidence was identified in the paitent.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cycle threshold (Ct) has been suggested as an approximate measure of initial viral burden. The utility of cycle threshold, at admission, as a predictor of disease severity has not been thoroughly investigated. Methods and findings: We conducted a retrospective study of SARS-CoV-2 positive, hospitalized patients from 3/26/2020 to 8/5/2020 who had SARS-CoV-2 Ct data within 48 hours of admission (n = 1044). Only patients with complete survival data, discharged (n = 774) or died in hospital (n = 270), were included in our analysis. Laboratory, demographic, and clinical data were extracted from electronic medical records. Multivariable logistic regression was applied to examine the relationship of patient mortality with Ct values while adjusting for established risk factors. Ct was analyzed as continuous variable and subdivided into quartiles to better illustrate its relationship with outcome. Cumulative incidence curves were created to assess whether there was a survival difference in the setting of the competing risks of death versus patient discharge. Mean Ct at admission was higher for survivors (28.6, SD = 5.8) compared to non-survivors (24.8, SD = 6.0, P<0.001). In-hospital mortality significantly differed (p<0.05) by Ct quartile. After adjusting for age, gender, BMI, hypertension and diabetes, increased cycle threshold was associated with decreased odds of in-hospital mortality (0.91, CI 0.89–0.94, p<0.001). Compared to the 4th Quartile, patients with Ct values in the 1st Quartile (Ct <22.9) and 2nd Quartile (Ct 23.0–27.3) had an adjusted odds ratio of in-hospital mortality of 3.8 and 2.6 respectively (p<0.001). The discriminative ability of Ct to predict inpatient mortality was found to be limited, possessing an area under the curve (AUC) of 0.68 (CI 0.63–0.71). Conclusion: SARS-CoV-2 Ct was found to be an independent predictor of patient mortality. However, further study is needed on how to best clinically utilize such information given the result variation due to specimen quality, phase of disease, and the limited discriminative ability of the test. [ABSTRACT FROM AUTHOR]

B. Extensive bone marrow necrosis evident on histological sections taken from the autopsy gl Marrow sections from autopsy showed ill-defined necrotic cells with amorphous eosinophilic necrotic debris (Figure 1(B)), consistent with marrow necrosis. Bone marrow necrosis and fat embolism syndrome in sickle cell disease: Increased susceptibility of patients with non-SS genotypes and a possible association with human parvovirus B19 infection. Fat embolism syndrome secondary to bone marrow necrosis in patients with hemoglobinopathies. [Extracted from the article]

Background: Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has a variable clinical course with significant mortality. Early reports suggested higher rates of SARS‐CoV‐2 infection in patients with type A blood and enrichment of type A individuals among COVID‐19 mortalities. Study Design and Methods: The study includes all patients hospitalized or with an emergency department (ED) visit who were tested for SARS‐CoV‐2 between March 10, 2020 and June 8, 2020 and had a positive test result by nucleic acid test (NAT) performed on a nasopharyngeal swab specimen. A total of 4968 patients met the study inclusion criteria, with a subsequent 23.1% (n = 1146/4968) all‐cause mortality rate in the study cohort. To estimate overall risk by ABO type and account for the competing risks of in‐hospital mortality and discharge, we calculated the cumulative incidence function (CIF) for each event. Cause‐specific hazard ratios (csHRs) for in‐hospital mortality and discharge were analyzed using multivariable Cox proportional hazards models. Results: Type A blood was associated with the increased cause‐specific hazard of death among COVID‐19 patients compared to type O (HR = 1.17, 1.02–1.33, p =.02) and type B (HR = 1.32,1.10–1.58, p =.003). Conclusions: Our study shows that ABO histo‐blood group type is associated with the risk of in‐hospital death in COVID‐19 patients, warranting additional inquiry. Elucidating the mechanism behind this association may reveal insights into the susceptibility and/or immunity to SARS‐CoV‐2. [ABSTRACT FROM AUTHOR]

Axicabtagene ciloleucel (Axi-cel) is a CD-19 Chimeric Antigen Receptor T cell therapy approved for the treatment of relapsed/refractory diffuse large B cell lymphoma. We treated ten patients with DLBCL post-FDA approval in an inner-city tertiary center in the Bronx. Eight patients (80%) had received ≥ 3 lines of therapy, six patients had received prior radiation, and seven had recurrent disease after prior autologous hematopoietic stem cell transplant (AHCT). Our cohort included one patient with HIV, two patients with hepatitis B, and two patients with CNS involvement of lymphoma. Axi-cel treatment led to significant responses with 8/10 patients achieving a complete remission at 3 months, including both patients with prior CNS involvement. The treatment was generally well tolerated with 20% of patients experiencing grade ≥ 2 CRS. One patient each with HIV and hepatitis B responded without significant toxicities. In conclusion, Axi-cel led to significant efficacy with manageable toxicity in DLBCL in a real-world setting. [ABSTRACT FROM AUTHOR]