Plasma exchange as a tool for removal of bevacizumab: Highlighting application for urgent surgery.

Background: Bevacizumab is commonly used to manage cerebral edema associated with brain tumors. However, its long half-life poses challenges for patients requiring urgent surgery due to wound complications. We present a case of utilizing therapeutic plasma exchange (TPE) to remove bevacizumab in a patient with recurrent glioblastoma requiring urgent surgery. Methods: A 58-year-old male with recurrent glioblastoma, IDH-wildtype, presented with clinical and radiographic concern for ventriculitis requiring urgent wound washout only 4 days after his last bevacizumab infusion. TPE was performed for 3 sessions after surgery using a centrifugation-based cell separator. Replacement fluids included normal serum albumin, normal saline, and fresh frozen plasma. Bevacizumab levels were quantified using an enzyme-linked immunoabsorbent assay before and after each TPE session. Results: TPE effectively removed bevacizumab, enabling safe surgery without new complications. Plasma bevacizumab levels decreased from 1087.63 to 145.35 ng/mL (13.4% of original) by the end of the last TPE session. This decline is consistent with nearly 3 half-lives, which compares favorably to the expected timeline of natural decline given the 21-day half-life. Conclusions: We report a complex clinical scenario of a patient requiring urgent wound washout 4 days after last bevacizumab infusion for CNS infection. Surgery was successfully performed without new complications with use of TPE to remove bevacizumab immediately following surgery. This case highlights the feasibility of this approach, which may be utilized effectively in patients requiring surgery after having recently received bevacizumab.

Rates Among Hospitalized Patients With COVID-19 Treated With Convalescent Plasma: A Systematic Review and Meta-Analysis.

Objective: To examine the association of COVID-19 convalescent plasma transfusion with mortality and the differences between subgroups in hospitalized patients with COVID-19. Patients and Methods: On October 26, 2022, a systematic search was performed for clinical studies of COVID-19 convalescent plasma in the literature from January 1, 2020, to October 26, 2022. Randomized clinical trials and matched cohort studies investigating COVID-19 convalescent plasma transfusion compared with standard of care treatment or placebo among hospitalized patients with confirmed COVID-19 were included. The electronic search yielded 3841 unique records, of which 744 were considered for full-text screening. The selection process was performed independently by a panel of 5 reviewers. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data were extracted by 5 independent reviewers in duplicate and pooled using an inverse-variance random effects model. The prespecified end point was all-cause mortality during hospitalization. Results: Thirty-nine randomized clinical trials enrolling 21,529 participants and 70 matched cohort studies enrolling 50,160 participants were included in the systematic review. Separate meta-analyses reported that transfusion of COVID-19 convalescent plasma was associated with a decrease in mortality compared with the control cohort for both randomized clinical trials (odds ratio [OR], 0.87; 95% CI, 0.76-1.00) and matched cohort studies (OR, 0.76; 95% CI, 0.66-0.88). The meta-analysis of subgroups revealed 2 important findings. First, treatment with convalescent plasma containing high antibody levels was associated with a decrease in mortality compared with convalescent plasma containing low antibody levels (OR, 0.85; 95% CI, 0.73 to 0.99). Second, earlier treatment with COVID-19 convalescent plasma was associated with a decrease in mortality compared with the later treatment cohort (OR, 0.63; 95% CI, 0.48 to 0.82). Conclusion: During COVID-19 convalescent plasma use was associated with a 13% reduced risk of mortality, implying a mortality benefit for hospitalized patients with COVID-19, particularly those treated with convalescent plasma containing high antibody levels treated earlier in the disease course.

The effect of plasma exchange on serum levels of lacosamide: A case report.

PURPOSE: We describe the case of a 22-year-old male who developed thyroid storm necessitating therapeutic plasma exchange (TPE). The patient's past medical history was complicated by epilepsy, for which he took lacosamide. Little evidence was available to guide lacosamide dosing during TPE. Because of an exacerbation of the patient's underlying epilepsy in the context of the thyroid storm, we conducted therapeutic medication monitoring of lacosamide concentrations to guide management. SUMMARY: We arranged for measurement of the lacosamide concentration immediately before TPE (5.1 µg/mL) and 2.5 hours after the initial measurement (3.4 µg/mL) to determine the amount of lacosamide removed by TPE. Utilizing population pharmacokinetic parameters, we calculated the expected concentration and compared this to the measured concentration. The difference between these values was used to determine the percentage removed via TPE compared to the expected post-TPE concentration. We found that one TPE session removed an additional 20% of serum lacosamide. CONCLUSION: TPE appeared to remove an additional 20% of lacosamide when compared to the expected post-TPE concentration.

Complement gene variant effect on relapse of complement-mediated thrombotic microangiopathy after eculizumab cessation.

Eculizumab is effective for complement-mediated thrombotic microangiopathy (CM-TMA), also known as atypical hemolytic uremic syndrome. Although lifelong therapy had been suggested, discontinuation does not universally lead to relapse. Comprehensive data evaluating risk factors for recurrence following discontinuation are limited. Our aim was to systematically review available literature assessing the role of complement genetic variants in this setting. Reports on CM-TMA and eculizumab withdrawal published before 1 January 2021, were included. Key reasons for patient exclusion were no follow-up after drug withdrawal and patients lacking complement genetic testing. Two-hundred eighty patients from 40 publications were included. Median age was 28 years, and 25 patients had a known history of renal transplant. Complement genetic variants were identified in 60%, most commonly in CFH (n = 59) and MCP/CD46 (n = 38). Of patients with a complement gene variant, 51.3% had ≥1 likely pathogenic/pathogenic variant whereas the remaining had variants of uncertain significance (VUS). Overall relapse rate after therapy discontinuation was 29.6%. Relapse rate was highest among patients with CFH variants and MCP/CD46 variants in canonical splice regions. VUS (P < .001) and likely pathogenic/pathogenic variants (P < .001) were associated with increased relapse. Presence of a renal allograft (P = .009); decreasing age (P = .029); and detection of variants in CFH (P < .001), MCP/CD46 (P < .001), or C3 (P < .001) were all independently associated with relapse after eculizumab discontinuation. Eculizumab discontinuation is appropriate in specific patients with CM-TMA. Caution should be exerted when attempting such a strategy in patients with high risk of recurrence, including a subgroup of patients with MCP/CD46 variants.

Plasma exchange in the intensive care unit: a narrative review.

In this narrative review, we discuss the relevant issues of therapeutic plasma exchange (TPE) in critically ill patients. For many conditions, the optimal indication, device type, frequency, duration, type of replacement fluid and criteria for stopping TPE are uncertain. TPE is a potentially lifesaving but also invasive procedure with risk of adverse events and complications and requires close monitoring by experienced teams. In the intensive care unit (ICU), the indications for TPE can be divided into (1) absolute, well-established, and evidence-based, for which TPE is recognized as first-line therapy, (2) relative, for which TPE is a recognized second-line treatment (alone or combined) and (3) rescue therapy, where TPE is used with a limited or theoretical evidence base. New indications are emerging and ongoing knowledge gaps, notably regarding the use of TPE during critical illness, support the establishment of a TPE registry dedicated to intensive care medicine.

Clinical Practice Guidelines From the Association for the Advancement of Blood and Biotherapies (AABB): COVID-19 Convalescent Plasma.

DESCRIPTION: Coronavirus disease 2019 convalescent plasma (CCP) has emerged as a potential treatment of COVID-19. However, meta-analysis data and recommendations are limited. The Association for the Advancement of Blood and Biotherapies (AABB) developed clinical practice guidelines for the appropriate use of CCP. METHODS: These guidelines are based on 2 living systematic reviews of randomized controlled trials (RCTs) evaluating CCP from 1 January 2019 to 26 January 2022. There were 33 RCTs assessing 21 916 participants. The results were summarized using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method. An expert panel reviewed the data using the GRADE framework to formulate recommendations. RECOMMENDATION 1 (OUTPATIENT): The AABB suggests CCP transfusion in addition to the usual standard of care for outpatients with COVID-19 who are at high risk for disease progression (weak recommendation, moderate-certainty evidence). RECOMMENDATION 2 (INPATIENT): The AABB recommends against CCP transfusion for unselected hospitalized persons with moderate or severe disease (strong recommendation, high-certainty evidence). This recommendation does not apply to immunosuppressed patients or those who lack antibodies against SARS-CoV-2. RECOMMENDATION 3 (INPATIENT): The AABB suggests CCP transfusion in addition to the usual standard of care for hospitalized patients with COVID-19 who do not have SARS-CoV-2 antibodies detected at admission (weak recommendation, low-certainty evidence). RECOMMENDATION 4 (INPATIENT): The AABB suggests CCP transfusion in addition to the usual standard of care for hospitalized patients with COVID-19 and preexisting immunosuppression (weak recommendation, low-certainty evidence). RECOMMENDATION 5 (PROPHYLAXIS): The AABB suggests against prophylactic CCP transfusion for uninfected persons with close contact exposure to a person with COVID-19 (weak recommendation, low-certainty evidence). GOOD CLINICAL PRACTICE STATEMENT: CCP is most effective when transfused with high neutralizing titers to infected patients early after symptom onset.

Rescuing Cancer Immunity by Plasma Exchange in Metastatic Melanoma (ReCIPE-M1): protocol for a single-institution, open-label safety trial of plasma exchange to clear sPD-L1 for immunotherapy.

BACKGROUND: Patients with metastatic melanoma rely on PD-(L)1 immunotherapy, but only one-third of patients experience treatment response and all initial responders eventually develop resistance. Tumour-derived extracellular vesicles expressing Programmed death ligand 1 (evPD-L1) and soluble Programmed death ligand 1 (sPD-L1) in peripheral blood of patients with melanoma limit PD-(L)1 immunotherapy and correlate with poor survival. Therapeutic plasma exchange (TPE) removes immunosuppressive evPD-L1 and sPD-L1. We hypothesise that TPE may rescue and restore antimelanoma immunity. METHODS: In this two-arm study, 60 patients with metastatic melanoma progressing on checkpoint inhibition will be accrued. All patients will undergo radiotherapy on days 1-5 (at least one measurable lesion will not be irradiated) and ongoing checkpoint inhibition on day 8 and every 2-3 weeks per standard of care. Patients with baseline sPD-L1 level of ≥1.7 ng/mL and adequate clinical capacity will be enrolled in the TPE intervention arm and will undergo TPE on days 5-7, in addition to standard of care radiotherapy and immunotherapy. Other patients will remain in the standard of care arm.The primary endpoint of the study is to evaluate safety. Secondary endpoints include kinetics of sPD-L1 and evPD-L1 and clinical response by RECIST (Response Evaluation Criteria in Solid Tumors) criteria. Study registered at ClinicalTrials.gov (NCT04581382). ETHICS AND DISSEMINATION: This trial has been approved by the Mayo Clinic Institutional Review Board. It will assess the safety and feasibility of TPE in improving outcomes for PD-(L)1 inhibitor immunotherapy in melanoma. Data will be maintained on a secure database with deidentified patient information. Data will be shared on publication in a peer-reviewed journal without the aid of professional writers. If successful, this trial will lay the ground for phase II studies that will include cancer treated with PD-(L)1 inhibitors which may benefit from TPE such as renal, bladder and lung cancers. TRIAL REGISTRATION NUMBER: NCT04581382.

Considerations for immune effector cell therapy collections: a white paper from the American Society for Apheresis.

BACKGROUND AIMS: This white paper was developed to provide leukapheresis guidance for the collection of mononuclear cells from adult and pediatric patients who are destined for immune effector cell (IEC) therapies for commercial and research applications. Currently, there is considerable variability in leukapheresis processes and limited published information regarding best practices relevant to new cellular therapies, especially IECs. Herein the authors address critical leukapheresis questions in five domains to help guide consistent collection processes and ensure high-quality products. The first four domains are onboarding, pre-collection, collection and post-collection, with protocol feasibility, preparation, care and follow-up of the patient/donor at each step, respectively, and technical considerations during collection. The fifth domain of quality assurance focuses on ensuring product potency, purity, safety and auditing. METHODS: The American Society for Apheresis (ASFA) Clinical Applications Committee (IEC Therapy Subcommittee) was charged by the society's board of directors with working collaboratively with other ASFA committees and organizations, including the Foundation for the Accreditation of Cellular Therapy, Association for the Advancement of Blood and Biotherapies, American Society for Transplantation and Cellular Therapy, National Marrow Donor Program and International Society for Cell & Gene Therapy, to develop guidelines regarding leukapheresis collection of cells destined for the manufacture of IEC therapies. After a review of the literature and discussion with members of the involved committees and various institutions, a draft guidance was created and circulated for comment and revision. RESULTS: Critical aspects of apheresis that could affect the quality and quantity of the leukapheresis product were identified. These areas were then discussed and reviewed. After consensus, the best practice guidelines were proposed and accepted. CONCLUSIONS: In the current era of rapid growth of IEC therapies, it is important to address critical leukapheresis steps to provide high-quality products and more consistent practices and to eliminate redundant efforts.

Coagulation profile of human COVID-19 convalescent plasma.

Convalescent plasma is used to treat COVID-19. There are theoretical concerns about the impact of pro-coagulant factors in convalescent plasma on the coagulation cascade particularly among patients with severe COVID-19. The aim of this study was to evaluate the coagulation profile of COVID-19 convalescent plasma. Clotting times and coagulation factor assays were compared between fresh frozen plasma, COVID-19 convalescent plasma, and pathogen-reduced COVID-19 convalescent plasma. Measurements included prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen, D-dimer, von Willebrand factor activity, von Willebrand factor antigen, coagulation factors II, V, VII-XII, protein S activity, protein C antigen, and alpha-2 plasmin inhibitor. Clotting times and coagulation factor assays were not different between COVID-19 convalescent plasma and fresh frozen plasma, except for protein C antigen. When compared to fresh frozen plasma and regular convalescent plasma, pathogen reduction treatment increased activated partial thromboplastin time and thrombin time, while reducing fibrinogen, coagulation factor II, V, VIII, IX, X, XI, XII, protein S activity, and alpha-2 plasmin inhibitor. The coagulation profiles of human COVID-19 convalescent plasma and standard fresh frozen plasma are not different. Pathogen reduced COVID-19 convalescent plasma is associated with reduction of coagulation factors and a slight prolongation of coagulation times, as anticipated. A key limitation of the study is that the COVID-19 disease course of the convalesced donors was not characterized.

Comparison of hematopoietic progenitor cell collection using different inlet flow rates with the Fenwal Amicus.

PURPOSE: We have used a hematopoietic progenitor cell (HPC) algorithm (standard [STD]) that restricted the inlet flow rate to 65 mL/min for peripheral white blood cell count (PWBC) >35 × 109 /L (STD). In this study, we evaluated a technique that allows 85 mL/min, regardless of the PWBC count (high). For patients with PWBC >35 × 109 /L, a prospective, randomized comparison of the high flow rate vs the STD PWBC-based flow rate (65 mL/min) was performed, comparing CD34+ and lymphocyte yields, collection efficiencies (CE1), mononuclear cells (MNC), and granulocytes, red blood cell (RBC), and platelet content. METHODS: The Fenwal Amicus version 4.5 with a heparinized ACD-A anticoagulant (AC) delivered at a 26:1 AC ratio was used. Paired comparisons between high and STD techniques were assessed with Wilcoxon signed rank tests, with P < .05 considered significant. Data are summarized as medians. RESULTS: Forty patient pairs (autologous) were compared. Diagnoses included primarily multiple myeloma (60%) and lymphoma (37.5%). High had significantly higher median average inlet rates (69 vs 55 mL/min), whole blood processed (20 vs 16 L), and cycles (15 vs 14) than STD. There were no significant differences in pre-procedure counts. Collection contents were (high/STD): 306/328 × 106 CD34+ cells, 48/59% CD34+ CE1 (significant), 0.2/0.2 × 109 /kg lymphocytes, 45/57% lymphocyte CE1, 63/59 × 109 WBC, 15/16 × 109 granulocytes, and 1.9/1.7 × 1011 platelets. CONCLUSIONS: The simpler, standardized high flow technique did not significantly increase or decrease CD34+ cells or lymphocyte yields, but did significantly decrease CD34+ CE1. The effects on cross-cellular content were minimal and not clinically significant.

Lack of defined apheresis collection criteria in publicly available CAR-T cell clinical trial descriptions: Comprehensive review of over 600 studies.

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.

IMPROvE-CED Trial: Intracoronary Autologous CD34+ Cell Therapy for Treatment of Coronary Endothelial Dysfunction in Patients With Angina and Nonobstructive Coronary Arteries.

BACKGROUND: Coronary endothelial dysfunction (CED) causes angina/ischemia in patients with nonobstructive coronary artery disease (NOCAD). Patients with CED have decreased number and function of CD34+ cells involved in normal vascular repair with microcirculatory regenerative potential and paracrine anti-inflammatory effects. We evaluated safety and potential efficacy of intracoronary autologous CD34+ cell therapy for CED. METHODS: Twenty NOCAD patients with invasively diagnosed CED and persistent angina despite maximally tolerated medical therapy underwent baseline exercise stress test, GCSF (granulocyte colony stimulating factor)-mediated CD34+ cell mobilization, leukapheresis, and selective 1×105 CD34+ cells/kg infusion into left anterior descending. Invasive CED evaluation and exercise stress test were repeated 6 months after cell infusion. Primary end points were safety and effect of intracoronary autologous CD34+ cell therapy on CED at 6 months of follow-up. Secondary end points were change in Canadian Cardiovascular Society angina class, as-needed sublingual nitroglycerin use/day, Seattle Angina Questionnaire scores, and exercise time at 6 months. Change in CED was compared with that of 51 historic control NOCAD patients treated with maximally tolerated medical therapy alone. RESULTS: Mean age was 52±13 years; 75% were women. No death, myocardial infarction, or stroke occurred. Intracoronary CD34+ cell infusion improved microvascular CED (%acetylcholine-mediated coronary blood flow increased from 7.2 [-18.0 to 32.4] to 57.6 [16.3-98.3]%; P=0.014), decreased Canadian Cardiovascular Society angina class (3.7±0.5 to 1.7±0.9, Wilcoxon signed-rank test, P=0.00018), and sublingual nitroglycerin use/day (1 [0.4-3.5] to 0 [0-1], Wilcoxon signed-rank test, P=0.00047), and improved all Seattle Angina Questionnaire scores with no significant change in exercise time at 6 months of follow-up. Historic control patients had no significant change in CED. CONCLUSIONS: A single intracoronary autologous CD34+ cell infusion was safe and may potentially be an effective disease-modifying therapy for microvascular CED in humans. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03471611.

Access to and safety of COVID-19 convalescent plasma in the United States Expanded Access Program: A national registry study.

BACKGROUND: The United States (US) Expanded Access Program (EAP) to coronavirus disease 2019 (COVID-19) convalescent plasma was initiated in response to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19. While randomized clinical trials were in various stages of development and enrollment, there was an urgent need for widespread access to potential therapeutic agents. The objective of this study is to report on the demographic, geographical, and chronological characteristics of patients in the EAP, and key safety metrics following transfusion of COVID-19 convalescent plasma. METHODS AND FINDINGS: Mayo Clinic served as the central institutional review board for all participating facilities, and any US physician could participate as a local physician-principal investigator. Eligible patients were hospitalized, were aged 18 years or older, and had-or were at risk of progression to-severe or life-threatening COVID-19; eligible patients were enrolled through the EAP central website. Blood collection facilities rapidly implemented programs to collect convalescent plasma for hospitalized patients with COVID-19. Demographic and clinical characteristics of all enrolled patients in the EAP were summarized. Temporal patterns in access to COVID-19 convalescent plasma were investigated by comparing daily and weekly changes in EAP enrollment in response to changes in infection rate at the state level. Geographical analyses on access to convalescent plasma included assessing EAP enrollment in all national hospital referral regions, as well as assessing enrollment in metropolitan areas and less populated areas that did not have access to COVID-19 clinical trials. From April 3 to August 23, 2020, 105,717 hospitalized patients with severe or life-threatening COVID-19 were enrolled in the EAP. The majority of patients were 60 years of age or older (57.8%), were male (58.4%), and had overweight or obesity (83.8%). There was substantial inclusion of minorities and underserved populations: 46.4% of patients were of a race other than white, and 37.2% of patients were of Hispanic ethnicity. Chronologically and geographically, increases in the number of both enrollments and transfusions in the EAP closely followed confirmed infections across all 50 states. Nearly all national hospital referral regions enrolled and transfused patients in the EAP, including both in metropolitan and in less populated areas. The incidence of serious adverse events was objectively low (<1%), and the overall crude 30-day mortality rate was 25.2% (95% CI, 25.0% to 25.5%). This registry study was limited by the observational and pragmatic study design that did not include a control or comparator group; thus, the data should not be used to infer definitive treatment effects. CONCLUSIONS: These results suggest that the EAP provided widespread access to COVID-19 convalescent plasma in all 50 states, including for underserved racial and ethnic minority populations. The study design of the EAP may serve as a model for future efforts when broad access to a treatment is needed in response to an emerging infectious disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT#: NCT04338360.

The report from ASFA COVID-19 taskforce: Considerations and prioritization on apheresis procedures during the SARS-CoV-2 coronavirus disease (COVID-19) pandemic.

Since vaccination for SARS-CoV-2 coronavirus started, the trajectory of patient numbers infected with the virus has improved once; however, variants of SARS-CoV-2 have emerged and more people have been infected; therefore, pandemic status is still far from resolution. Government and social efforts to prevent coronavirus infection continue in most states in the US and globally even after the Centers for Disease Control and Prevention declared some restriction relief for fully vaccinated people in March 2021. Healthcare institutions and various professional organizations have developed guidelines or policies to prevent the spread of these coronaviruses in the setting of apheresis. In this report, the issues that apheresis services may encounter under the current COVID-19 (SARS-CoV-2 coronavirus disease) pandemic will be discussed with potential strategies that can be adapted for efficient and optimum use of apheresis resources.

Mortality in individuals treated with COVID-19 convalescent plasma varies with the geographic provenance of donors.

Successful therapeutics and vaccines for coronavirus disease 2019 (COVID-19) have harnessed the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Evidence that SARS-CoV-2 exists as locally evolving variants suggests that immunological differences may impact the effectiveness of antibody-based treatments such as convalescent plasma and vaccines. Considering that near-sourced convalescent plasma likely reflects the antigenic composition of local viral strains, we hypothesize that convalescent plasma has a higher efficacy, as defined by death within 30 days of transfusion, when the convalescent plasma donor and treated patient were in close geographic proximity. Results of a series of modeling techniques applied to approximately 28,000 patients from the Expanded Access to Convalescent Plasma program (ClinicalTrials.gov number: NCT04338360) support this hypothesis. This work has implications for the interpretation of clinical studies, the ability to develop effective COVID-19 treatments, and, potentially, for the effectiveness of COVID-19 vaccines as additional locally-evolving variants continue to emerge.

Laboratory Medicine and Pathology Education During the COVID-19 Pandemic-Lessons Learned.

The rapidly spreading COVID-19 pandemic demanded immediate organizational pivots in departments of laboratory medicine and pathology, including development and implementation of severe acute respiratory syndrome coronavirus 2 diagnostics in the face of unprecedented supply chain shortages. Laboratory medicine and pathology educational programs were affected in numerous ways. Here, we overview the effects of COVID-19 on the large, academic Department of Laboratory Medicine and Pathology educational practice at Mayo Clinic, highlighting lessons learned for the post-pandemic era and planning for the possibility of a future pandemic.

Infused Autograft Absolute Lymphocyte Count Predicts Superior Survival in Diffuse Large B Cell Lymphoma Patients Post-Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation: A Matched Case-Control Study.

Our group published a double phase III trial showing that patients infused with an autograft absolute lymphocyte count (A-ALC) ≥0.5 × 109 cells/kg experienced superior survival post-autologous peripheral blood hematopoietic stem cell transplantation (APBHSCT). Based on the results from our phase III study, as well as published retrospective studies, on April 1, 2017, our Bone Marrow Transplant Program changed our standard practice to collect an A-ALC ≥0.5 × 109 cells/kg in addition to stem cells for lymphoma patients undergoing APBHSCT. The primary objective of the present study was to continue to assess the prognostic ability of A-ALC by evaluating overall survival (OS) and progression-free survival (PFS) of diffuse large B cell lymphoma (DLBCL) patients who underwent APBHSCT after April 1, 2017, compared with matched control groups at a 1:1:1 ratio with DLBCL patients infused with an A-ALC <0.5 × 109 cells/kg and A-ALC ≥0.5 × 109 cells/kg before April 1, 2017. Using the GREEDY algorithm, 85 DLBCL patients (cases) infused with an A-ALC ≥0.5 × 109 cells/kg after April 1, 2017, were matched at a 1:1:1 ratio with control groups of DLBCL patients who underwent transplantation before April 1, 2017: patients infused with an A-ALC <0.5 × 109 cells/kg (control 1) and patients infused with an A-ALC ≥0.5 × 109 cells/kg (control 2) before April 1, 2017. Groups were matched in terms of sex, age, stage, lactate dehydrogenase (LDH) level, performance status, extranodal disease, International Prognostic Index (IPI), and disease status before APBHSCT (complete or partial response). Survival follow-up was truncated at 3 years from the date of transplantation. Cases, control 1, and control 2 were balanced as to age (P = .8), sex (P = .9), LDH (P = .6), performance status (P = .5), extranodal disease (P = .2), IPI (P = .6), and disease status before APBHSCT (P = .2). Cases and control 2 showed superior OS and PFS compared with control 1. Multivariate analysis including all patients continued to show A-ALC ≥0.5 × 109 cells/kg as an independent predictor for OS (hazard ratio [HR], 0.382; 95% confidence interval [CI], 0.241 to 0.605; P < .0001) and PFS (HR, 0.437; 95% CI, 0.279 to 0.629; P < .0001). Our matched case-control study supports the results of previously published retrospective studies and our phase III study showing that the infusion of A-ALC is a prognostic factor for survival in DLBCL patients undergoing APBHSCT. Our findings support the practice of collecting not only enough stem cells for hematologic engraftment, but also enough immune effector cells (ie, A-ALC) to improve clinical outcomes in DLBCL patients post-APBHSCT.

Program and patient characteristics for the United States Expanded Access Program to COVID-19 convalescent plasma.

BACKGROUND: The United States (US) Expanded Access Program (EAP) to COVID-19 convalescent plasma was initiated in response to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease-2019 (COVID-19). While randomized clinical trials were in various stages of development and enrollment, there was an urgent need for widespread access to potential therapeutic agents particularly for vulnerable racial and ethnic minority populations who were disproportionately affected by the pandemic. The objective of this study is to report on the demographic, geographic, and chronological access to COVID-19 convalescent plasma in the US via the EAP. METHODS AND FINDINGS: Mayo Clinic served as the central IRB for all participating facilities and any US physician could participate as local physician-principal investigator. Registration occurred through the EAP central website. Blood banks rapidly developed logistics to provide convalescent plasma to hospitalized patients with COVID-19. Demographic and clinical characteristics of all enrolled patients in the EAP were summarized. Temporal trends in access to COVID-19 convalescent plasma were investigated by comparing daily and weekly changes in EAP enrollment in response to changes in infection rate on a state level. Geographical analyses on access to convalescent plasma included assessing EAP enrollment in all national hospital referral regions as well as assessing enrollment in metropolitan and less populated areas which did not have access to COVID-19 clinical trials.From April 3 to August 23, 2020, 105,717 hospitalized patients with severe or life-threatening COVID-19 were enrolled in the EAP. A majority of patients were older than 60 years of age (57.8%), male (58.4%), and overweight or obese (83.8%). There was substantial inclusion of minorities and underserved populations, including 46.4% of patients with a race other than White, and 37.2% of patients were of Hispanic ethnicity. Severe or life-threatening COVID-19 was present in 61.8% of patients and 18.9% of patients were mechanically ventilated at time of convalescent plasma infusion. Chronologically and geographically, increases in enrollment in the EAP closely followed confirmed infections across all 50 states. Nearly all national hospital referral regions enrolled patients in the EAP, including both in metropolitan and less populated areas. CONCLUSIONS: The EAP successfully provided widespread access to COVID-19 convalescent plasma in all 50 states, including for underserved racial and ethnic minority populations. The efficient study design of the EAP may serve as an example framework for future efforts when broad access to a treatment is needed in response to a dynamic disease affecting demographic groups and areas historically underrepresented in clinical studies.