High CD34-positive cell dose in matched unrelated donor allogeneic hematopoietic stem cell transplant is not associated with graft-versus-host disease or mortality.

BACKGROUND: CD34+ stem cells serve as the primary graft source for allogeneic transplants, with a minimum of 2-4 × 106 cells/kg needed for engraftment. There are conflicting data on outcomes at high stem cell doses, with studies limited by few patients receiving doses far above the minimum target. STUDY DESIGN AND METHODS: In this retrospective, single-center study of patients with hematologic malignancies who underwent matched unrelated donor transplants, we assessed outcomes for engraftment, survival, relapse, and graft-versus-host disease (GVHD) for the highest CD34+ dose quintile (>13 × 106 cells/kg, n = 36) compared to the remaining patients (n = 139). Similar analysis was performed correlating T cell dose and outcomes. RESULTS: There was no difference between the groups in neutrophil engraftment, with a trend toward faster platelet engraftment. There was no significant difference in mortality (adjusted risk ratio [aRR] = 1.02, 95% confidence interval [CI] = 0.85-1.22), relapse (aRR = 1.10, 95% CI = 0.85-1.42), or overall survival by Kaplan-Meier analysis (p = .44). High CD34+ dose was not associated with higher incidence of acute GVHD (aRR = 0.99 grades II-IV, aRR = 1.18 grades III-IV) or chronic GVHD (aRR = 0.87 overall, RR = 1.21 severe). There was limited correlation between CD34+ and T cell dose (R2 = .073), and there was no significant difference in survival, relapse, or GVHD in the highest T cell dose quintile (n = 33) compared to the remaining quintiles (n = 132). DISCUSSION: We found no difference in survival, relapse, or GVHD incidence or severity in patients receiving CD34+ doses above prior cutoffs reported in the literature. These data do not support the routine use of graft CD34+ dose reduction.

Clinical consequences of a 30-day interval between antibody identifications.

BACKGROUND: While studies have shown that antibody detection may be delayed if an antibody identification (ABID) is not performed every 3 days, little data exist on the potential major risk of an acute hemolytic transfusion reaction (aHTR). STUDY DESIGN AND METHODS: At our institution, if no change in the screen, or a positive crossmatch, ABIDs are performed every 30 days. Between January 1, 2015 and May 31, 2019, all new antibodies detected within 28 days of a prior transfusion were identified. Testing results and patient charts were reviewed for evidence of hemolysis. The $211 patient charge was used to determine the cost for ABIDs performed during the studied time period. RESULTS: For 36 patients, a new clinically significant alloantibody was detected within 28 days of an antigen-positive transfusion. Only one of these patients had a history of prior alloimmunization and put at possible risk due to the ABID policy. For this patient, while there was less than the expected increment to an antigen-positive unit, there was no clinical or laboratory evidence of an aHTR. During this same time, 6095 ABIDs were performed, at a cost of approximately $1.29 million, and 72,665 red cell transfusions occurred. CONCLUSION: With an ABID every 30 days, only one patient, over 4.5 years, was put at potential risk for hemolysis from one transfusion (0.001% of the total units transfused during the time period). While antibody detection may be delayed, performing ABIDs every 30 days saves money and medical laboratory scientist time and should be balanced against potential patient harm.

Current advances in 2022: A critical review of selected topics by the Association for the Advancement of Blood and Biotherapies (AABB) Clinical Transfusion Medicine Committee.

BACKGROUND: The Association for the Advancement of Blood and Biotherapies Clinical Transfusion Medicine Committee (CTMC) composes a summary of new and important advances in transfusion medicine (TM) on an annual basis. Since 2018, this has been assembled into a manuscript and published in Transfusion. STUDY DESIGN AND METHODS: CTMC members selected original manuscripts relevant to TM that were published electronically and/or in print during calendar year 2022. Papers were selected based on perceived importance and/or originality. References for selected papers were made available to CTMC members to provide feedback. Members were also encouraged to identify papers that may have been omitted initially. They then worked in groups of two to three to write a summary for each new publication within their broader topic. Each topic summary was then reviewed and edited by two separate committee members. The final manuscript was assembled by the first and senior authors. While this review is extensive, it is not a systematic review and some publications considered important by readers may have been excluded. RESULTS: For calendar year 2022, summaries of key publications were assembled for the following broader topics within TM: blood component therapy; infectious diseases, blood donor testing, and collections; patient blood management; immunohematology and genomics; hemostasis; hemoglobinopathies; apheresis and cell therapy; pediatrics; and health care disparities, diversity, equity, and inclusion. DISCUSSION: This Committee Report reviews and summarizes important publications and advances in TM published during calendar year 2022, and maybe a useful educational tool.

Current advances in transfusion medicine 2021: A critical review of selected topics by the AABB Clinical Transfusion Medicine Committee.

BACKGROUND: Each year the AABB Clinical Transfusion Medicine Committee (CTMC) procures a synopsis highlighting new, important, and clinically relevant studies in the field of transfusion medicine (TM). This has been made available as a publication in Transfusion since 2018. METHODS: CTMC members reviewed and identified original manuscripts covering TM-related topics published electronically (ahead-of-print) or in print from December 2020 to December 2021. Selection of publications was discussed at committee meetings and chosen based on perceived relevance and originality. Next, committee members worked in pairs to create a synopsis of each topic, which was then reviewed by additional committee members. The first and senior authors assembled the final manuscript. Although this synopsis is extensive, it is not exhaustive, and some articles may have been excluded or missed. RESULTS: The following topics are included: blood products; convalescent plasma; donor collections and testing; hemoglobinopathies; immunohematology and genomics; hemostasis; patient blood management; pediatrics; therapeutic apheresis; and cell therapy. CONCLUSIONS: This synopsis highlights and summarizes recent key developments in TM and may be useful for educational purposes.

Anesthesiology Resident Knowledge of Transfusion Medicine: Results From the Anesthesiology Transfusion Education Study.

BACKGROUND: Transfusion of blood products is a common practice in anesthesiology. Inadequate transfusion medicine knowledge may lead to inappropriate transfusion practices and patient risk. Using a validated assessment tool modified for anesthesiology, we conducted a survey of anesthesiology residents in the United States to assess transfusion medicine knowledge. METHODS: A validated transfusion medicine examination and accompanying survey were forwarded by program directors to residents for anonymous completion on May 5 and closed on June 30, 2021. The outcome of interest was the mean examination score. Secondary areas of interest were performance by year of training and previous educational experience in transfusion reported by the trainees. Rasch analysis was performed on the examination quality and individual question performance. Kruskal-Wallis H tests were used to identify differences between mean scores. Post hoc comparisons were used to assess specific pairwise differences between mean test scores by survey variable. RESULTS: Four hundred twenty-three anesthesiology residents in 37 programs completed the examination. The mean score was 45.5% ± 12.6%. There was a significant difference in mean cumulative examination scores between different resident training levels (P < 0.001). There was a significant difference in scores between clinical anesthesia (CA)-1 and CA-2 residents (P = 0.011) and CA-1 and CA-3 residents (P = 0.012). No significant difference in examination scores was observed between CA-2 and CA-3 residents (P = 0.95). All these subgroups scored below 50% on the examination. Significant differences between the residency training programs and cumulative scores were identified (P < 0.001). CONCLUSIONS: This examination highlights gaps in transfusion medicine knowledge within US anesthesiology residents. Targeted education may improve knowledge in this area and patient care.

Call for improvement in medical school training in genetics: results of a national survey.

PURPOSE: To assess, from the student perspective, medical school training in genetics and genomics. METHODS: In 2019, the Undergraduate Training in Genomics (UTRIG) Working Group developed genetics-related survey and knowledge questions for the RISE-FIRST, an exam administered to postgraduate year 1 (PGY1) pathology residents in the United States during their first months of training. Survey questions focused on perceived knowledge in genetics and the structure and quality of training with responses compared with those in control areas. RESULTS: There were 401 PGY1 pathology residents who took the 2019 RISE-FIRST (65% of those in the United States). There was significantly lower perceived understanding of genetics compared with nongenetics topics. Respondents also reported less time spent learning genetics and lower quality training compared with control areas. Only 53% indicated an interaction during medical school with a medical geneticist. Residents also did not perform as well on the UTRIG-developed knowledge questions than those in other areas of pathology. CONCLUSION: The RISE-FIRST is a useful tool in assessing the current state of medical school training in genetics. This needs assessment may serve as a call to action to improve medical school genetics education and promote greater understanding of the role of genetics professionals in patient care.

Pediatric resident knowledge of transfusion medicine: Results from the BEST-TEST3 international education needs assessment.

BACKGROUND: Transfusions are a common intervention within pediatrics and require unique considerations to optimize patient care. Poor knowledge of evidence-based transfusion practice can lead to misuse of transfusion therapy and harm. While there have been assessments of transfusion medicine knowledge of physicians caring for adult patients, there is little data regarding pediatricians. STUDY DESIGN AND METHODS: Using a published transfusion medicine knowledge exam for internal medicine physicians as a backbone, pediatric transfusion medicine experts, using an iterative process, developed a pediatric-specific examination. Pilot testing and Rasch analysis, a method used in high-stakes testing, was used to validate the exam. The exam and a previously validated survey on transfusion medicine training, attitudes, and perceived ability were administered to pediatric residents. Analysis consisted of descriptive statistics as well as comparisons of exam scores based on survey responses. RESULTS: 330 pediatric residents from 19 sites in 6 countries participated in the study. The vast majority (91%) of residents had obtained blood product consent. The mean exam score was 37.1% (range 9.5%-71.4%) with no statistical differences based on amount or perceived quality of transfusion medicine education or perceived ability. DISCUSSION: A rigorously validated exam has now been developed that can be used to assess pediatric transfusion medicine knowledge. A large international group of pediatric residents performed poorly on the exam demonstrating a pressing need for improved transfusion medicine education to ensure safe and appropriate administration of blood components to infants and children.

Lack of impact of umbilical cord blood unit processing techniques on clinical outcomes in adult double cord blood transplant recipients.

BACKGROUND AIMS: Despite widespread use of umbilical cord blood (UCB) transplantation and distinct practice preferences displayed by individual UCB banks and transplant centers, little information exists on how processing variations affect patient outcomes. METHODS: We reviewed 133 adult double UCB transplants performed at a single center: 98 after reduced-intensity and 35 after myeloablative conditioning. Processing associated with contributing UCB banks and units was surveyed to identify differences in practice. We analyzed effect of selected variables on clinical outcomes of engraftment, dominance, transplant-related mortality, and survival. RESULTS: Eighty-eight percent of banks queried currently practice red blood cell (RBC) depletion before cryopreservation. This reflects a shift in practice because previously 65% of banks employed RBC-replete processing methods (i.e., cryopreservation or plasma/volume reduction). Neither neutrophil nor platelet engraftment was affected by processing conditions analyzed. RBC depletion was not associated with clinical outcomes, except in 17 recipients of 2 RBC-replete units, where survival was better than that observed in 116 recipients of ≥1 RBC-depleted units (hazard ratio 3.26, P = 0.004). When analyzed by attributes of the dominant unit, RBC depletion, time in storage, bank years in existence, and inventory size did not affect clinical outcomes. Postthaw viability and CD34 dose were factors impacting engraftment. Notably, all RBC-replete units in this cohort were washed in dextran-human serum albumin before infusion. DISCUSSION: These findings support continued utilization of the entire existing pool of cord blood units, despite recent trends in processing, and have important implications for banking resources and UCB selection practices.

The National Cancer Institute R25 Cancer Education Grants Program: A Workshop Report.

Through the R25 Cancer Education Grants Program (CEGP), the National Cancer Institute (NCI) has been supporting the broad educational needs of the cancer research and cancer healthcare communities since 1974. NCI sponsored a workshop on September 13, 2016 in Bethesda, Maryland, with the objectives of sharing best practices in cancer education, communicating R25 CEGP programmatic information, and gathering ideas to strengthen the R25 CEGP to better meet the emerging needs in cancer education in the face of a rapidly changing landscape in cancer research and cancer care. With 53 leaders in cancer education in attendance, the workshop featured an overview of the R25 CEGP by NCI Program Staff, a showcase of several types of CEGP programs by current R25 grantees, and in-depth discussions on a broad range of questions critical for the continued success of the R25 CEGP. The workshop afforded an opportunity, for the first time, for cancer researchers and clinicians conducting different forms of cancer education activities to gather in one place as leaders of a community of increasing importance. The discussion resulted in a set of suggestions that will benefit the R25 CEGP and cancer education in general. There was a general consensus among the participants that bringing the cancer education community together is a significant achievement of the workshop that will have a long-lasting impact on cancer education.

BEST-TEST2: assessment of hematology trainee knowledge of transfusion medicine.

BACKGROUND: As transfusion is a common therapy and key component in every hematologist's practice, hematology training programs should dedicate significant time and effort to delivering high-quality transfusion medicine education to their trainees. The current state of hematology trainee knowledge of transfusion medicine is not known. STUDY DESIGN AND METHODS: A validated assessment tool developed by the Biomedical Excellence for Safer Transfusion (BEST) Collaborative was used to assess prior transfusion medicine education, attitudes, perceived ability, and transfusion medicine knowledge of hematology trainees. RESULTS: A total of 149 hematology trainees at 17 international sites were assessed. The overall mean exam score was 61.6% (standard deviation, 13.4%; range, 30%-100%) with no correlation in exam scores with postgraduate year or previous transfusion medicine education in medical school or internal medicine residency. However, better scores correlated with 3 or more hours of transfusion medicine education (p = 0.0003) and perceived higher-quality education during hematology training (p = 0.03). Hematology trainees at US sites, where hematology is often combined with oncology training, had statistically lower scores than trainees at non-US sites (56.2% vs. 67.4%; p < 0.0001). In terms of topic areas, although 93% of participants had obtained consent for transfusion, the lowest scores were on transfusion reaction-related questions. CONCLUSION: Given the overall poor performance, this study serves as an impetus for all hematology training programs to reevaluate the quality and quantity of transfusion medicine training and can assist in the development of targeted curricula.

Provision of KEL1-negative blood to obstetric patients: a 3-year single-institution retrospective review.

BACKGROUND: KEL1 alloimmunization is a major cause of hemolytic disease of the fetus and newborn (HDFN). While select countries have guidelines for preventing transfusion-associated KEL1 alloimmunization, the United States does not. Beth Israel Deaconess Medical Center instituted a policy in April 2009 whereby women not more than 50 years of age on the obstetric service were transfused KEL1-negative red blood cells (RBCs). We sought to determine compliance and impact for prevention of KEL1 alloimmunization and HDFN. STUDY DESIGN AND METHODS: All women not more than 50 years of age without anti-K transfused RBCs during an obstetric admission from April 9, 2009, to April 9, 2012, were identified (227). Adherence to policy, factors contributing to nonadherence, and subsequent impact were evaluated. For comparison, all cases of anti-K detection in women not more than 50 years of age admitted to nonobstetric services and all cases of transfusion-associated KEL1 alloimmunization in women not more than 50 years of age during the 10 years prior were identified. RESULTS: Eighty-four percent received only KEL1-negative units. Three (1.3%) women not more than 50 years of age on the obstetric service were identified with anti-K, while 17 (1.5%) women not more than 50 years of age on nonobstetric services had anti-K detected; only five of 20 had a prior RBC transfusion. In the 10 years prior, there were 27 cases of transfusion-associated KEL1 alloimmunization in women not more than 50 years of age. There were no cases of KEL1 HDFN in either period. CONCLUSION: Although the findings demonstrate feasibility of providing KEL1-negative RBCs to women of childbearing potential, evidence for clinical benefit is lacking. The low prevalence of KEL1 in blood donors, the lack of significant differences in alloimmunization rates, and no cases of HDFN during the study period questions the clinical benefit of such a policy.

Internal medicine resident knowledge of transfusion medicine: results from the BEST-TEST international education needs assessment.

BACKGROUND: Blood transfusion is the most common hospital procedure performed in the United States. While inadequate physician transfusion medicine knowledge may lead to inappropriate practice, such an educational deficit has not been investigated on an international scale using a validated assessment tool. Identifying specific deficiencies is critical for developing curricula to improve patient care. STUDY DESIGN AND METHODS: Rasch analysis, a method used in high-stakes testing, was used to validate an assessment tool consisting of a 23-question survey and a 20-question examination. The assessment tool was administered to internal medicine residents to determine prior training, attitudes, perceived ability, and actual knowledge related to transfusion medicine. RESULTS: A total of 474 residents at 23 programs in nine countries completed the examination. The overall mean score of correct responses was 45.7% (site range, 32%-56%). The mean score for Postgraduate Year (PGY)1 (43.9%) was significantly lower than for PGY3 (47.1%) and PGY4 (50.6%) residents. Although 89% of residents had participated in obtaining informed consent from a patient for transfusion, residents scored poorly (<25% correct) on questions related to transfusion reactions. The majority of residents (65%) would find additional transfusion medicine training "very" or "extremely" helpful. CONCLUSION: Internationally, internal medicine residents have poor transfusion medicine knowledge and would welcome additional training. The especially limited knowledge of transfusion reactions suggests an initial area for focused training. This study not only represents the largest international assessment of transfusion medicine knowledge, but also serves as a model for rigorous, collaborative research in medical education.

Anti-D alloimmunization after D-incompatible platelet transfusions: a 14-year single-institution retrospective review.

BACKGROUND: A small, but immunogenic dose of red blood cells (RBCs) may be contained in apheresis platelets (PLTs). Attempts are made to provide D- recipients with D- PLTs to prevent anti-D alloimmunization and the potential for hemolytic disease of the fetus and newborn. Beth Israel Deaconess Medical Center has a policy that when necessary to transfuse D+ PLTs to D- patients, we recommend that RhIG be given when the patient is a woman of child-bearing age or a potential liver transplant patient. We sought to retrospectively determine the rate of anti-D formation after D-incompatible apheresis PLT transfusions in those patients not receiving RhIG and not receiving D+ RBCs over a 14-year period at our institution. STUDY DESIGN AND METHODS: All D- patients (626) who received D+ prestorage leukoreduced apheresis PLTs between January 1, 1997, and December 31, 2011, were identified. Those patients who received RhIG (45), D+ RBC transfusions (50), or stem cell transplantation from a D+ donor (16); had prior anti-D (23); or had unresolved Rh at admission (8) were not eligible for analysis. Only those patients who had an antibody screen performed at least 4 weeks after the incipient PLT transfusion were evaluated (130). RESULTS: Of 130 eligible D- patients, 48% women and 57% immunocompetent, who received a total of 565 apheresis PLTs, none formed anti-D. CONCLUSION: These findings support the use of D+ apheresis PLTs without RhIG irrespective of D status in all recipients.

Development of a validated exam to assess physician transfusion medicine knowledge.

BACKGROUND: There is evidence that physicians lack adequate transfusion medicine knowledge. To design needs-based educational interventions to address this gap, a validated assessment tool is required. Previously published exams have not been created or validated using rigorous psychometric methods. STUDY DESIGN AND METHODS: A modified Delphi method was used to achieve consensus regarding the essential knowledge and skills for physicians who transfuse blood products. To ensure content validity, members of an international organization of transfusion medicine experts (Biomedical Excellence for Safer Transfusion [BEST] Collaborative) participated in the exam design process. An exam, based on the most highly rated topics, was created and administered to individuals with a priori expected basic, intermediate, and expert levels of transfusion medicine knowledge. Rasch analysis, a psychometric technique used in high-stakes medical licensure and board testing, was used to determine exam accuracy and precision. RESULTS: Thirty-six topics achieved ratings sufficient to be considered for inclusion in the exam (content validity index > 0.8). A 23-question exam was administered to 49 individuals. Mean scores for individuals with expected basic, intermediate, and expert knowledge were 42, 62, and 82%, respectively (p < 0.0001). The exam achieved good fit with the Rasch model. CONCLUSION: A validated exam has now been created to accurately assess transfusion medicine knowledge. This exam can be used to determine knowledge deficits and assist in the design of curricula to improve blood product utilization.

Examining Injustices: Transfusion Medicine and Race.

Race and ethnicity are sociopolitical and not biological constructs, and assertions that these population descriptors have scientific meaning has caused significant harm. A critical assessment of the transfusion medicine literature is an important aspect of promoting race-conscious as opposed to race-based medicine. Utilizing current definitions and health equity frameworks, this review will provide a critical appraisal of transfusion medicine studies at the intersection of race and healthcare disparities, with a focus on larger methodological challenges facing the transfusion medicine community. Moving forward, risk modelling accounting for upstream factors, patient input, as well as an expert consensus on how to critically conduct and evaluate this type of literature are needed. Further, when using race and ethnicity in research contexts, investigators must be aware of existing guidelines for such reporting.