Safety and Feasibility of Third-Party Cytotoxic T Lymphocytes for High-Risk Patients with Covid-19.

Cytotoxic T lymphocytes (CTLs) destroy virally infected cells and are critical for the elimination of viral infections such as those caused by the SARS-CoV-2 virus. Delayed and dysfunctional adaptive immune responses to SARS-CoV-2 are associated with poor outcomes. Treatment with allogeneic SARS-CoV-2-specific CTLs may enhance cellular immunity in high-risk patients and provide a safe, direct mechanism of treatment. Thirty high-risk ambulatory patients with COVID-19 were enrolled on a phase I trial to assess the safety of 3rd party, SARS-CoV-2-specific CTLs. Twelve Interventional patients, 6 of whom were immunocompromised, matched the human leukocyte antigen (HLA)-A*02:01 restriction of the CTLs and received a single infusion of one of four escalating doses of a product containing 68.5% SARS-CoV-2-specific CD8+ CTLs/total cells. Symptom improvement and resolution in these patients was compared to an Observational group of eighteen patients lacking HLA-A*02:01 who could receive standard of care. No dose-limiting toxicities were observed at any dosing level. Nasal swab PCR data showed ≥ 88% and >99% viral elimination from baseline in all patients at 4- and 14-days post-infusion. The CTLs did not interfere with the development of endogenous anti-SARS-CoV-2 humoral or cellular responses. T-cell receptor beta (TCR) analysis comparing SARS-CoV-2-specific T-cell responses derived from the CTL donor versus recipients showed persistence of donor-derived CTLs through the end of the 6-month follow-up period. Interventional patients consistently reported symptomatic improvement 2-3 days after infusion, whereas improvement was more variable in Observational patients. This study shows that SARS-CoV-2-specific CTLs are a potentially feasible cellular therapy for COVID-19 illness. (Clinicaltrials.gov #NCT04765449).

Successful treatment of pure red cell aplasia using therapeutic plasma exchange after ABO-incompatible hematopoietic stem cell transplant.

Hematopoietic stem cell transplants (HSCTs) are widely used in the treatment of hematologic malignancies and bone marrow failure syndromes. ABO compatibility is typically of secondary importance, and up to 50% of HSCT are performed in ABO-incompatible pairings. In the literature, pure red cell aplasia (PRCA) occurs in 1% to 50% of all major/bidirectional ABO-incompatible stem cell transplants, but treatment of PRCA remains heterogeneous. Here, we report two cases in which patients with transfusion-dependent PRCA following HSCT were successfully treated with therapeutic plasma exchange (TPE). Case 1: A 52-year-old type O-positive male with acute myeloid leukemia underwent HSCT using apheresis-derived HSCs from a fully human leukocyte antigen (HLA)-matched, related type A-positive male donor. He developed PRCA that was refractory to multiple therapies, so a series of 10 TPE was performed over 3 weeks. Case 2: A 21-year-old type A-positive male with aplastic anemia underwent HSCT using bone marrow-derived HSCs from a fully HLA-matched related type B-positive female donor. He developed PRCA that was refractory to multiple therapies, so a series of 5 TPE was performed over 2 weeks. Case 1: The patient has been transfusion independent since TPE #7, and type A red blood cells (RBCs) were seen on the ABO type after TPE #9. Case 2: The patient has been transfusion independent since after TPE #1, and type B RBCs were seen on the ABO type after TPE #5. TPE was successful in treating two patients with PRCA after ABO-incompatible HSCT transplants. Isoagglutinin titers decreased below the level of detection for both our patients. Ultimately both patients became transfusion independent and showed evidence of erythroid cell recovery.

Optimizing Utilization of Blood Products in the Hematologic Malignancy Clinic: Less Is More.

PURPOSE: There are no universal guidelines for blood product transfusions in patients with hematologic malignancies (HMs). Excess utilization of platelet and RBC transfusion in patients with HM increases the cost of care and likelihood of adverse events. We aim to decrease the total number of transfused units and multiunit orders of platelets and RBCs in the HM clinic by 25% from March 2020 to December 2020. METHODS: A multidisciplinary, interprofessional team was formed. Baseline rates of blood product utilization were determined using Qlik Analytic software. Strategies to improve utilization were developed, and three interventions were initiated. Data were collected on monthly intervals. Data for total number of platelet and RBC units ordered, total multiunit orders, average number of units ordered per encounter, and pretransfusion hemoglobin thresholds were collected from May 2019 to December 2020. RESULTS: Through our Plan-Do-Study-Act cycles from March 2020 to December 2020, the total number of platelet transfusion orders per month decreased from 164 to 98, multiunit platelet orders decreased from 63 to 2, and the average number of platelet transfusions per encounter decreased from 1.62 to 1.03. The total number of RBC transfusion orders decreased from 172 to 141, multiunit RBC orders decreased from 25 to 16, and the average number of RBC transfusions per encounter decreased from 1.21 to 1.18. CONCLUSION: Implementation of our multidisciplinary interventions led to more appropriate use of blood products in the outpatient setting. Ongoing efforts are underway to continue to improve utilization in the inpatient and outpatient setting.

The impact of HLA donor-specific antibodies on engraftment and the evolving desensitization strategies.

The majority of contemporary allogeneic hematopoietic stem cell transplantation (HCT) procedures utilize partially HLA-mismatched stem cell grafts. Donor-specific anti-HLA antibodies (DSA) are associated with primary graft failure independent of the graft source, conditioning intensity and other patient and donor factors. Here we provide an update on testing and monitoring of DSA, review the impact of DSA on stem cell engraftment, and present promising desensitization modalities. Ultimately, we attempt to provide practical recommendations for DSA screening and mitigation strategies.

Update in Transfusion Medicine Education.

Despite the high frequency with which blood transfusions are performed, transfusion medicine education remains variable in the United States and around the world. Educating medical students and nonpathology physicians is critical for safe and evidence-based transfusion. Many innovative curricula have been published to meet the needs of physicians training in a variety of specialties. Learners' knowledge can be assessed using validated knowledge assessment tools and objective structured clinical examinations. In this review, transfusion medicine curricula and assessment tools are reviewed. Strategies for virtual teaching and learning are also introduced.

Therapeutic plasma exchange in patients with severe obesity (BMI >40): A survey of practices in the United States.

BACKGROUND: The prevalence of obesity in the United States is estimated at 42.4% and expected to increase over the next decade. Therefore, understanding how to best perform certain medical procedures on severely obese (SO) patients is a necessity. This study presents results on the current methods of performing therapeutic plasma exchange (TPE) on SO patients. This paper aims to contribute to the existing literature by providing new insights into calculating plasma volume (PV) for TPE in SO patients. METHODS: Blood Bank/Apheresis Directors at all institutions with pathology residency and/or blood banking/transfusion medicine fellowship programs were asked to complete a 5-question online survey about their institutional policies regarding TPE in SO patients. Survey data were analyzed to determine if institutions have policies in place to calculate PV in SO patients. RESULTS: Out of the 144 institutions contacted, 45 (31%) completed the survey. Nine (20%) institutions had a policy to calculate PV differently for SO patients, 7 (16%) reported a specific body mass index (BMI) above which they alter PV calculation, and 7 (16%) reported a maximum volume exchanged in SO patients. CONCLUSION: A minority of responding institutions had specific policies in place to calculate PV for TPE in SO patients. Practice patterns for calculating PV for TPE in SO patients varied, with some institutions adjusting PV calculations and others setting a maximum volume to be exchanged regardless of BMI. These findings highlight the need for establishing a clear method of calculating PV in SO patients.

How do I perform therapeutic phlebotomy?

BACKGROUND: Therapeutic phlebotomy (TP) is a well-established medical intervention that evolved from the historical practice of bloodletting. METHODS: Patients who require TP are not infrequently told by their health-care providers to "just go donate blood," but TP should always be offered in the context of a prescribed course of therapy. Providers can prescribe a course of TP for a number of indications, including hereditary hemochromatosis, polycythemia vera, iron overload, and testosterone replacement therapy. RESULTS: A course of prescribed TP specifies that patients can be phlebotomized more frequently than volunteer blood donors and reassures patients that TP is being performed per the orders of their provider. Prescribed TP also facilitates two-way communication between the referring provider and the transfusion medicine (TM) physician overseeing the TP. The College of American Pathologists TM checklist describes several requirements regarding the documentation and performance of TP, and electronic medical record systems can be used to demonstrate compliance with these requirements. CONCLUSIONS: TM physicians should discuss the advantages of prescribing TP with providers who mutually care for patients requiring this intervention.

Educational Case: A Case of Transfusion-Transmitted Babesiosis: Diagnostic Perspectives Across the Clinical Laboratory.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.1.

The role of therapeutic plasma exchange in clinically amyopathic dermatomyositis with MDA-5 antibody: A case report and review of the literature.

Clinically amyopathic dermatomyositis (CADM) is a rare, aggressive variant of dermatomyositis associated with interstitial lung disease (ILD) and refractoriness to immunosuppressants. Antibodies against melanoma differentiation-associated gene 5 (MDA-5) are often found in patients with CADM. We report a patient with advanced CADM with ILD and MDA-5 antibodies who failed to improve with immunosuppressants. We performed 2 TPE over 3 days, using 5% albumin as replacement fluid. Although five total TPE were planned, he was transferred for lung transplant evaluation after the second TPE; he died 16 days after transfer without receiving a transplant. A literature review identified four patients with CADM and MDA-5 antibodies treated with TPE; all experienced symptomatic improvement of their ILD. We attribute our patient's outcome to the advanced nature of his disease rather than a failure of TPE. Additional research may indicate a possible reclassification of CADM with MDA-5 antibodies in future ASFA guidelines.

Transfusion Rates and the Utility of Type and Screen for Pelvic Organ Prolapse Surgery.

OBJECTIVES: Limited data exist directly comparing the likelihood of blood transfusion by route of apical pelvic organ prolapse (POP) surgery. In addition, limited evidence is available regarding the risk of not ordering preoperative type and screen (T&S) in apical POP surgery. The objectives of the study are to (1) provide baseline data regarding the current need for preoperative T&S by comparing perioperative blood transfusion rates between 3 routes of apical POP surgery and (2) determine the rate of a positive preoperative antibody screen in women who underwent apical POP surgery. METHODS: This was a retrospective cohort study of women who underwent apical POP surgery by 3 different routes: abdominal (abdominal sacrocolpopexy), robotic (robotic sacrocolpopexy), or vaginal (uterosacral or sacrospinous ligament fixation). RESULTS: Among 610 women who underwent apical POP surgeries between May 2005 and May 2016, 24 women (3.9%) received a perioperative blood transfusion. The rate of transfusion was higher in the abdominal group (11.1%) compared with robotic (0.5%, P < 0.001) and vaginal (0.5%, P < 0.001). In a logistic regression model, abdominal route of POP surgery remained significantly associated with transfusion (odds ratio, 20.7; 95% confidence interval, 2.7-156.6). Among the 572 women who had a preoperative T&S performed, 9 (1.5%) had a positive antibody screen. CONCLUSIONS: Blood transfusion was significantly more common in abdominal compared with robotic and vaginal apical POP surgeries. The rate of a positive antibody screen was low, suggesting that type O blood is low risk if cross-matched blood is not available. Thus, it may be reasonable to not order a preoperative T&S prior to robotic or vaginal apical POP surgery.

Correlating Transfusion Medicine In-Service Examination Scores With Outcomes of the American Board of Pathology Transfusion Medicine Subspecialty Certifying Examination.

OBJECTIVES: The Transfusion Medicine In-Service Examination (TMISE) is offered twice a year to transfusion medicine (TM) fellows. We examined the relationship between TMISE scores and outcomes of the American Board of Pathology (ABP) TM subspecialty certifying examination (TM boards). METHODS: TM fellowship programs were contacted to provide anonymous data about TM fellows, their scores on TMISE, and outcome of TM boards. RESULTS: Of 48 TM fellowship programs contacted, 24 (50%) responded with data for 170 fellows. Average TMISE score of fellows who passed their first TM boards attempt was 71.3, while the average TMISE score of fellows who failed their first TM boards attempt was 64.3 (P = .009). CONCLUSIONS: TMISE scores correlated with passing TM boards on the first attempt. Fellows who took the TM boards the same year that they graduated from TM fellowship had a significantly higher first-time pass rate than fellows who delayed taking TM boards.

The Impact of an Undergraduate Biology Class on Donor Recruitment at a Hospital-Based Blood Donor Center.

OBJECTIVES: A biology class, BIOL 294H, taught undergraduates about platelet donation while partnering with the University of North Carolina's (UNC's) hospital-based Blood Donation Center to recruit apheresis platelet donors. We identified our platelet donors' demographics and learned how BIOL 294H affected recruitment. METHODS: Every platelet donor presenting to the UNC Blood Donation Center from February 7, 2017, to March 10, 2017, was asked to complete an electronic 10-question survey. RESULTS: A total of 159 unique donors completed the survey; 64% were female and 75% were between ages 18 and 25 years. Overall, 70% were UNC undergraduate students. Over half (56%) reported first learning about platelet donation through word of mouth, and 22% cited specific efforts associated with BIOL 294H. CONCLUSIONS: Recruitment of undergraduate platelet donors primarily included BIOL 294H peer interactions and deliverables from the class, such as social media updates and events on campus. The sustained recruiting efforts of our students over many years contributed to recruitment of a majority of our platelet donors.

Point-of-care versus central testing of hemoglobin during large volume blood transfusion.

BACKGROUND: Point-of-care (POC) hemoglobin testing has the potential to revolutionize massive transfusion strategies. No prior studies have compared POC and central laboratory testing of hemoglobin in patients undergoing massive transfusions. METHODS: We retrospectively compared the results of our point-of-care hemoglobin test (EPOC®) to our core laboratory complete blood count (CBC) hemoglobin test (Sysmex XE-5000™) in patients undergoing massive transfusion protocols (MTP) for hemorrhage. One hundred seventy paired samples from 90 patients for whom MTP was activated were collected at a single, tertiary care hospital between 10/2011 and 10/2017. Patients had both an EPOC® and CBC hemoglobin performed within 30 min of each other during the MTP. We assessed the accuracy of EPOC® hemoglobin testing using two variables: interchangeability and clinically significant differences from the CBC. The Clinical Laboratory Improvement Amendments (CLIA) proficiency testing criteria defined interchangeability for measurements. Clinically significant differences between the tests were defined by an expert panel. We examined whether these relationships changed as a function of the hemoglobin measured by the EPOC® and specific patient characteristics. RESULTS: Fifty one percent (86 of 170) of paired samples' hemoglobin results had an absolute difference of ≤7 and 73% (124 of 170) fell within ±1 g/dL of each other. The mean difference between EPOC® and CBC hemoglobin had a bias of - 0.268 g/dL (p = 0.002). When the EPOC® hemoglobin was < 7 g/dL, 30% of the hemoglobin values were within ±7, and 57% were within ±1 g/dL. When the measured EPOC® hemoglobin was ≥7 g/dL, 55% of the EPOC® and CBC hemoglobin values were within ±7, and 76% were within ±1 g/dL. EPOC® and CBC hemoglobin values that were within ±1 g/dL varied by patient population: 77% for cardiac surgery, 58% for general surgery, and 72% for non-surgical patients. CONCLUSIONS: The EPOC® device had minor negative bias, was not interchangeable with the CBC hemoglobin, and was less reliable when the EPOC® value was < 7 g/dL. Clinicians must consider speed versus accuracy, and should check a CBC within 30 min as confirmation when the EPOC® hemoglobin is < 7 g/dL until further prospective trials are performed in this population.

Dilution is not the solution: acute hemolytic transfusion reaction after ABO-incompatible pooled platelet transfusion.

CONCLUSIONS: The short shelf life of platelets makes providing ABO-compatible platelets a challenge, and many institutions issue ABO-incompatible platelets when compatible units are not available. It is presumed that ABO antibodies that exist in donor plasma are diluted when platelets from multiple donors are combined to make a pooled product for transfusion. We present a case of a hemolytic transfusion reaction in a 73-year-old man with myelodysplastic syndrome who received an ABO-incompatible pooled platelet unit. This case report demonstrates that the dilution theory is not always true for pooled platelet units, and any patient receiving ABO-incompatible platelet transfusions must be closely monitored for potential hemolytic transfusion reactions.