Red cell exchange for rapid leukoreduction in adults with hyperleukocytosis and leukostasis.

ABSTRACT: We show that red cell exchange (RCE) treats hyperleukocytosis in acute leukemia. RCE provided similar leukoreduction to standard therapeutic leukoreduction and could be superior in patients with severe anemia or monocytic leukemias or when requiring rapid treatment.

Gender differences in scholarly productivity of early-career transfusion medicine physicians.

BACKGROUND AND OBJECTIVES: Promotion in academic medicine requires evidence of the creation and dissemination of scholarly output, primarily through peer-reviewed publications. Studies demonstrate that scholarly activity and impact are lower for women physicians than for men physicians, especially during the early stages of their academic careers. This report reviewed physicians' academic productivity after passing their Blood Banking/Transfusion Medicine (BBTM) subspecialty exam to determine if gender discrepancies exist. METHODS: A cross-sectional analysis was designed to determine trends in scholarly activity for women physicians versus men physicians in BBTM. Indexed publications were reviewed using iCite, the National Institutes of Health (NIH) Office of Portfolio Analysis tool, from 1 January 2017 to 1 December 2021, for BBTM examinees who passed the sub-speciality fellowship exam in the years 2016 through 2018. RESULTS: Overall, women physicians had statistically significant fewer total career publications (median 6 vs. 9 cumulative papers, p = 0.03). Women published at a lower rate after passing BBTM boards, which was not statistically significant (0.7 vs. 1.3 publications per year). Other statistically significant findings include fewer early-career BBTM women physicians were first authors compared with men physicians (p = 0.03) and impact as assessed by relative citation ratio was higher for men (p = 0.01). CONCLUSIONS: This study demonstrates that there are gender differences in scholarly productivity and impact on early-career BBTM physicians. Given that this cohort of BBTM physicians are early-career professionals, the significant difference in first authorship publications between women and men physicians is especially concerning. Publication metrics should be followed to ensure equitable research environments for early-career BBTM physicians.

Effect of temporary storage of cryopreserved cellular therapy products at -80° celsius on cell recovery and viability.

Cellular therapy (CT) involving the transplantation of hematopoietic progenitor cells (HPC) is a treatment modality for both benign and malignant disorders. All autologous products require cryopreservation while allogeneic product cryopreservation became more common during the Coronavirus disease 2019 pandemic. Cells are stored in liquid nitrogen (LN2) freezers which can malfunction and products may have to be temporarily stored in a mechanical -80 °C freezer if additional LN2 freezer space is not available. The practice of temporary short-term -80 °C storage is present but there is no study to show that the product is unaffected by the temporary storage at a significantly warmer temperature. In this study, we identified previously collected CT products that were cryopreserved for now-deceased recipients that had remaining cryovials with aliquots of products for quality control purposes. Vials from 20 collections were split into 4 groups of 5 in with one vial placed in temporary storage at -80 °C for 2-5 weeks before returning to LN2 storage while another vial remained in LN2 storage for the entire duration of the study. The vials were then simultaneously thawed, processed, and evaluated for total nucleated cell (TNC) and CD34 + cell count and TNC and CD34 + cell viability to determine if there were any differences induced by temporary -80 °C storage. No statistically significant differences were seen after 4 weeks of -80 °C storage; however, after 5 weeks, a statistically significant decrease in TNC viability and viable TNC count, but not CD34 + cell viability and viable CD34 + cell count was observed. These results provide some reassurance to CT processing labs that if there is a failure in their LN2 storage for cryopreserved products, these products may be safely stored at -80 °C for up to 4 weeks and returned to LN2 storage without compromising CD34 + cell viability.

Apheresis practice variation during the COVID-19 pandemic: Results of a survey.

BACKGROUND: The COVID-19 pandemic affected healthcare delivery across all specialties including apheresis. To describe the changes in apheresis service practices that occurred during the pandemic, the American Society for Apheresis (ASFA) Apheresis Medicine Attending Physician Subcommittee conducted a survey study. STUDY DESIGN AND METHODS: A 32-question survey was designed and distributed to 400 ASFA physician members on September 7, 2022. Attending physicians responded to questions about whether and how apheresis service practices changed during the COVID-19 pandemic compared with the time period prior to the pandemic in terms of: (1) procedure types and volumes, (2) patient consultation workflow, and (3) the use of telemedicine. Descriptive analyses were reported as number and frequency of responses. RESULTS: The survey response rate was 13.8% (55/400). Of these respondents, 96.4% (53/55) were attending physicians. The majority of respondents (42/53, 79.2%) indicated that the types of procedures performed during COVID-19 compared to pre-pandemic did not change. Most frequently for apheresis procedure volume, respondents reported: no change in their monthly inpatient volume (21/47, 44.7%) and a decrease in their monthly outpatient volume (28/46, 60.9%). Prior to COVID-19, 75.0% (30/40) of respondents performed consultations at bedside for inpatients and 67.4% (29/43) performed consultations at bedside for outpatients. Bedside consultations decreased in both settings during the pandemic but were still most frequently performed by attending physicians. At the same time, the use of telemedicine increased for 15.4% of survey respondents during COVID-19. CONCLUSION: Some, but not all, respondents observed or made changes to their apheresis service during the COVID-19 pandemic. A subset of changes, such as increased utilization of telemedicine, may persist.

How do I manage a blood product shortage?

BACKGROUND: The demand for blood products sometimes exceeds the available inventory. Blood product inventories are dependent upon the availability of donors, supplies and reagents, and collection staff. During prolonged extreme shortages, blood centers and transfusion services must alter practices to meet the needs of patients. STUDY DESIGN AND METHODS: The Association for the Advancement of Blood and Biotherapies Donor and Blood Component Management Subsection compiled some strategies from its blood center and hospital transfusion service members that could be implemented during blood product shortages. RESULTS: Some strategies that blood centers could use to increase their available inventories include increasing donor recruitment efforts, using alternate types of collection kits, manufacturing low-yield apheresis-derived platelets and/or whole blood-derived platelets, using cold-stored platelets, transferring inventory internally among centers of the same enterprise, using frozen inventory, decreasing standing order quantities, prioritizing allocation to certain patient populations, filling partial orders, and educating customers and blood center staff. Transfusion service strategies that could be implemented to maximize the use of the limited available inventory include increasing patient blood management efforts, using split units, finding alternate blood suppliers, trading blood products with other hospital transfusion services, developing a patient priority list, assembling a hospital committee to decide on triaging priorities, using expired products in extreme situations, and accepting nonconforming products after performing safety checks. DISCUSSION: Blood centers and transfusion services must choose the appropriate strategies to implement based on their needs.

Apheresis medicine education during the early phase of the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic introduced challenges and disruption across healthcare, including apheresis medicine (AM). In this study, we report findings from a survey conducted among American Society for Apheresis Physician Committee (ASFA-PC) members to describe the impact of the COVID-19 pandemic on AM education practices. STUDY DESIGN AND METHODS: A voluntary, anonymous, 24-question, institutional review board-approved survey regarding AM teaching during the pandemic was distributed to ASFA-PC members in the United States between December 1, 2020, and December 15, 2020. Descriptive analyses were reported as number and frequency of respondents for each question. Free text responses were summarized. RESULTS: Responses were received from 14/31 (45%) of ASFA-PC members, of whom 12 practiced at academic institutions. Among these, 11/12 (92%) transitioned to virtual platform for AM trainee conferences during the pandemic. A variety of resources were employed to support independent AM learning. While 7/12 (58%) respondents did not change the informed consent process for AM procedures, others delegated this process or introduced remote alternatives. The most common method respondents used to conduct AM patient rounding was a hybrid in-person/virtual model. CONCLUSION: This survey describes the adaptations and changes AM practitioners made to trainee education in response to the early phase of the COVID-19 pandemic. The transition to virtual and/or hybrid trainee learning and AM rounds underscores the importance of digital AM resources. Further study of the effects of the pandemic and its impact on AM trainee education, as well as patient care is warranted.

Multicenter evaluation of the IL-3-pSTAT5 assay to assess the potency of cryopreserved stem cells from cord blood units: The BEST Collaborative study.

BACKGROUND: The IL-3-pSTAT5 assay, a new, rapid, and standardized flow-cytometry-based assay may compensate for several limitations of the colony-forming unit (CFU) assay typically used for stem cell potency assessments of cord blood units (CBU). We performed an inter-laboratory evaluation of the performance of this new assay. STUDY DESIGN AND METHODS: This Biomedical Excellence for Safer Transfusion (BEST) Collaborative multicenter, international study included 15 participants from public cord blood banks (CBBs), CBB-supporting research laboratories, and stem cell laboratories. To perform the IL-3-pSTAT5 assay, participating centers received reagents, instructions, and 10 blind CBU samples, including eight normal samples and two samples exposed to a transient warming event. We measured inter-laboratory agreement qualitatively (proportion of correctly classified samples) and quantitatively (coefficient of variation [CV], correlation coefficients, receiver operating characteristics (ROC) curve, and intraclass correlation coefficient [ICC]). RESULTS: The qualitative agreement was 97.3% (i.e., 107/110; Fleiss' kappa = 0.835). The average CV on a per-sample basis was 11.57% among all samples, 8.99% among normal samples, and on a per-center basis was 9.42% among normal samples. In a correlation matrix that compared results across centers, the mean Pearson's correlation coefficient was 0.88 (standard deviation = 0.04). The ICC was 0.83 (95% confidence interval = 0.68-0.95). The area under the curve (AUC) from the ROC curve was 0.9974. DISCUSSION: Excellent qualitative and quantitative agreement was exhibited across laboratories. The IL-3-pSTAT5 assay may therefore be implemented in flow cytometry laboratories to rapidly and reliably provide standardized measures of stem cell potency in CBUs.

Under the hood: The molecular biology driving gene therapy for the treatment of sickle cell disease.

Gene therapy will soon become the dominant modality for treating of sickle cell disease (SCD). Currently, three technologies are the most promising: expression of transgenic globin genes via a lentiviral vector, controlled mutation of the ß-globin control cluster by transgenic CRISPR-based ribonucleoprotein, and suppression of BCL11a mRNA by shRNA. In this review, we discuss the mechanism of each technology and how they correct the SCD pathology at the molecular level. We conclude by discussing potential directions future therapy may take.

Apheresis physician well-being during the COVID-19 pandemic: Results of a survey.

BACKGROUND: The COVID-19 pandemic has placed additional stressors on physician lives. In this study, we report findings from a survey conducted among attending physician (AP) members of the American Society for Apheresis (ASFA) to elucidate the status of their well-being during the COVID-19 pandemic as well as resources provided or actions taken by their institutions and themselves personally to maintain or improve their well-being. STUDY DESIGN AND METHODS: A 17-question, voluntary, IRB-approved survey regarding well-being was distributed to the ASFA AP members between August 26, 2020 and September 16, 2020. The descriptive analyses were reported as number and frequency of respondents for each question. Non-parametric chi-square tests, ANOVA, and paired t-tests were performed to determine differences in categorical variables, changes in well-being scores, and compare time points, respectively. RESULTS: Based on the responses of 70 attending level physicians representing the United States (U.S., 53, 75.7%) and outside the U.S. (17, 24.3%), the following were observed: (1) COVID-19 negatively affects the well-being of a sub-population of APs, (2) neither institutional nor individual measures to improve well-being completely resolved the problem of decreased AP well-being during the pandemic, and (3) personal actions may be superior to institutional resources. CONCLUSION: There is a widespread decline in AP well-being during the COVID-19 pandemic that was not adequately improved by institutional or personal resources/actions taken. Institutions and physicians must work together to implement strategies including resources and actions that could further improve AP physician well-being during a public health crisis.

Gene therapy for hemoglobinopathies.

Beta hemoglobinopathies such as sickle cell disease (SCD) and ß-thalassemia (BT) are the most common monogenic diseases worldwide. Both diseases are associated with significant morbidity and mortality. Because patients require lifelong follow-up and care, it also poses a serious burden in health services. Blood transfusions and/or drug therapy ameliorate the signs and symptoms of the disorders but are not curative. Allogeneic hematopoietic cell transplantation (HCT) is currently the only cure but it has several limitations including the paucity of human leukocyte antigen-matched related donors and a high risk of adverse events. Recent advances in hematopoietic stem cell based-gene therapy has made autologous HCT (auto-HCT) a reality. Clinical trials are underway using different gene transfer vectors and cassettes. Data obtained so far with a short-term follow-up has been very encouraging. Patients with SCD engrafted, had sustained production of the transgene and a decreased number of vaso-occlusive crises. Patients with BT were able to decrease the amount of transfusions required or stop transfusions all together. Adverse events observed were mostly associated with the myeloablative conditioning regimen. Long term data on gene persistence and toxicities are still needed. This review focuses on the current state of auto-HCT with gene therapy for SCD and BT. Current clinical trials and their outcome results are summarized.

How the COVID-19 pandemic changed cellular therapy at Columbia University Irving Medical Center/NewYork-Presbyterian Hospital.

New York is at the epicenter of the coronavirus disease 2019 (COVID-19) pandemic caused by the SARS-CoV-2 virus. Columbia University Irving Medical Center/NewYork-Presbyterian Hospital (CUIMC/NYPH) had to make changes to its cellular therapy operations to ensure patient, donor, and staff safety and well-being. In this article, we discuss the process changes we instituted for cellular therapy clinical care, collection, processing, and cryopreservation to cope with the rapidly evolving pandemic.

Red cell exchange for patients with sickle cell disease: an international survey of current practices.

INTRODUCTION: Red cell exchange (RCE) therapy is increasingly used to treat patients with acute or chronic manifestations of sickle cell disease (SCD). However, little is known regarding the most safe and effective practice parameters associated with this particular therapy. METHODS: A SCD subcommittee of members of the American Society for Apheresis (ASFA) developed a 122-question survey and administered it via email to other ASFA members. The survey inquired about clinical indications for treatment, practice patterns, and transfusion policies for RCE when used for patients with SCD. RESULTS: Ninety-nine distinct institutions completed the survey. Twenty-one (21%) were from outside of the US. Twenty-two (22%) provided chronic transfusion therapy to >10 patients, and both adult (25%) and pediatric-focused services (20%) were represented. Common acute indications for RCE included acute chest syndrome, acute ischemic stroke, and pre-surgical prophylaxis. Common chronic indications included primary stroke prophylaxis, secondary stroke prophylaxis, and recurrent acute chest syndrome. Respondents most commonly set a post-RCE treatment target of 30% for the hematocrit and hemoglobin S levels, regardless of the therapeutic indication. Units for RCE were phenotypically matched in 95% of cases. About 40% of respondents reported using isovolemic hemodilution. CONCLUSIONS: This survey solicited the current practice variations in RCE from a diverse range of practice sites. Many sites reported similar practice patterns and challenges but some variations emerged. To our knowledge, this survey represents the largest and most in-depth investigation of the use of RCE for patients with SCD, and could inform future studies in the field.

Hematopoietic stem cell transplantation and cellular therapy in sickle cell disease: where are we now?

PURPOSE OF REVIEW: Sickle cell disease (SCD) is a common monogenic disorder that is characterized by an A to T substitution in the ß-globin gene that leads to the production of hemoglobin S (HbS). Polymerization of HbS leads to significant morbidity including vaso-occlusion, pain, hemolytic anemia, and end organ damage. Allogeneic hematopoietic cell transplantation (allo-HCT) is the only curative treatment; however, suitable donors are not always readily available. This study reviews the current status of allo-HCT and autologous cellular therapies for SCD. RECENT FINDINGS: Alternative sources of allogeneic stem cells from unmatched donors such as cord blood and haploidentical donors are gaining traction. Early experience has shown that better conditioning regimens and graft-versus-host disease prophylaxis are needed before these donor sources can gain widespread use. Clinical trials are underway to determine the feasibility and efficacy of autologous transplantation with gene modified hematopoietic stem cells. Gene therapy strategies include HbS gene correction, gene addition, and hemoglobin F induction. Preliminary results are very encouraging. SUMMARY: Matched sibling allo-HCT for patients with SCD results in more than 90% overall survival and more than 80% event-free survival. Because only 25-30% of patients have a matched sibling donor, alternative donor options such as matched unrelated donors, related haploidentical donors and unrelated umbilical cord blood donors are being considered. Clinical trials investigating various strategies for gene therapy followed by autologous transplantation are underway. One major challenge is obtaining sufficient hematopoietic stem cells for gene therapy. Studies are being conducted on the optimal mobilization regimen and collection strategy.

More efficient exchange of sickle red blood cells can be achieved by exchanging the densest red blood cells: An ex vivo proof of concept study.

BACKGROUND: In sickle cell disease (SCD), red blood cells (RBCs) containing hemoglobin S can be denser than RBCs containing wild-type hemoglobin, especially when dehydrated. We hypothesize that targeting denser RBCs during red blood cell (RBC) exchange for SCD could result in more efficient removal of dehydrated, sickled RBCs and preservation of non-sickled RBCs. STUDY DESIGN AND METHODS: Waste products from RBC exchanges for SCD were used as "simulated patients". One RBC volume was exchanged using ABO-compatible blood. The apheresis instrument was programmed to exchange the entire RBC layer by indicating the hematocrit (control), or the bottom half by indicating the hematocrit was half the hematocrit (experimental), with or without subsequent transfusion. Hemoglobin S levels, and complete blood counts were measured. RESULTS: Hemoglobin S levels were lower after the modified versus control RBC exchange (post-RBC exchange mean 4.96% and 11.27%); total hemoglobin S amounts were also lower (mean 19.27 and 58.29 mL of RBCs). Mean RBC density decreased after the modified RBC exchange by 8.86%. Hematocrit decreased in the modified RBC exchange by 36.37%, with partial correction by direct transfusion following a truncated RBC exchange. CONCLUSIONS: Targeting denser RBCs in RBC exchange enhanced hemoglobin S removal and decreased RBC density. Further development of this ex vivo model could potentially allow for: 1) improved reduction in hemoglobin S levels (allowing for longer periods between RBC exchange or maintained lower levels), or 2) achievement of previous goal hemoglobin S levels with fewer donor units (reducing alloimmunization risk and improving blood utilization).

Vascular access practices for therapeutic apheresis: Results of a survey.

INTRODUCTION: Obtaining vascular access (VA) is a critical part of the therapeutic apheresis (TA) treatment plan. Currently, there are no guidelines for VA decision-making and maintenance related to TA procedures. MATERIALS AND METHODS: A 28-question survey to gather qualitative information regarding VA practices was distributed to the American Society for Apheresis (ASFA) 2018 Annual Meeting attendees and all ASFA members for voluntary participation. The descriptive analyses were reported as the number and frequency of responses for each question. RESULTS: Total participation was 206 with 147 (71.4%) answering some or all 16 VA focused questions. The majority of respondents were nurses or physicians (89.0%) at sites providing ≥100 procedures. The most common TA procedures were plasma exchange, red cell exchange, and leukocytapheresis. The VA evaluation was predominantly performed by the TA service (80.3%, 118/147). The majority of TA physicians and/or providers do not insert (91.7%, 132/144) or remove (81.2%, 117/143) VA catheters. When an emergent TA procedure is needed, the majority of respondents felt <2 hours was an acceptable turnaround time for VA placement (64.3%, 92/143). The most common anticoagulant for locking catheters and/or ports was heparin. The majority of TA services (54.3%, 76/140) collect data on aborted procedures due to catheter/line/port problems unrelated to infection, but only 41.4% (58/140) collect data on infections. CONCLUSION: VA contributes significantly to the overall risks associated with and the safety of TA. Our survey shows that there is substantial variation but common themes in TA VA practices. Several areas for future research may be identified.

Choosing Wisely for apheresis.

The Choosing Wisely campaign has stimulated clinicians to think about the appropriateness of various tests and procedures, compelling physicians to make smarter, safer and more effective choices for high quality patient care and to reduce healthcare cost. The American Society for Apheresis (ASFA) strives to advance apheresis medicine through education, evidence-based practice, research and advocacy. To complement these shared missions, ASFA created a working group, consisting of representatives from the various ASFA committees, to produce recommendations for apheresis medicine that reflect the Choosing Wisely guiding principles. A diverse group of ASFA physician and allied health members reviewed, rated and ranked 9 original draft proposals. Additional revisions and refinements were made prior to external review and adoption of five final recommendations by the ASFA Board of Directors. The ASFA Choosing Wisely recommendations encourage apheresis practitioners, patients and donors to discuss and prioritize best clinical practices that avoid harm and waste while optimizing clinical benefit.

Novel therapeutic approaches for thrombotic thrombocytopenic purpura.

PURPOSE OF REVIEW: Acquired thrombotic thrombocytopenic purpura is an immune-mediated thrombotic microangiopathy caused by antibodies to ADAMTS13 (A Disintegrin And Metalloproteinase with a ThromboSpondin type 1 motif, member 13). Standard treatment with therapeutic plasma exchange and immunosuppression with steroids results in high remission and low mortality rates. However, a number of patients remain refractory to frontline therapy and/or experience multiple relapses. This study reviews emerging therapies for thrombotic thrombocytopenic purpura. RECENT FINDINGS: Studies indicate that reducing anti-ADAMTS13 antibody levels through B-cell depletion or proteasome inhibition is effective for the management of refractory disease. Preliminary reports examining anti-CD20 therapy for the treatment of initial disease or as maintenance therapy for seropositive patients suggest the addition of immunosuppression in other disease phases may delay relapse. Exciting developments in targeted therapies to von Willebrand Factor and recombinant ADAMTS13 hold promise for transforming disease management. SUMMARY: Approximately half of patients diagnosed with acquired thrombotic thrombocytopenic purpura experience refractory and/or relapsing disease. For these patients, a hematologic remission may be an insufficient therapeutic goal. With recent developments, it is now possible to envision a multifaceted approach targeting disease mechanisms that may dramatically improve outcomes for this otherwise debilitating disease.