Packed Red Blood Cell Transfusion Research Articles

Impact of Concomitant Traumatic Pancreatic and Colon Injuries on Outcomes.

Colon and pancreatic injuries have both long been independently associated with intraabdominal infectious complications in trauma patients. The goal of this study was to evaluate the impact of concomitant pancreatic injury on outcomes in patients with traumatic colon injuries. Consecutive patients over a 3-year period who underwent operative management of colon injuries were identified. Patient characteristics, severity of injury and shock, presence and grade of pancreatic injury, and intraoperative packed red blood cell (PRBC) transfusions were recorded. Outcomes including intraabdominal abscess formation and suture line failure were collected and compared. Multivariable logistic regression analysis was then performed to determine the impact of concomitant pancreatic injury on intraabdominal abscess formation. 243 patients with traumatic colon injuries were identified. 17 of these also had pancreatic injuries. Patients with combined colon and pancreatic injuries were clinically similar to those with isolated colon injuries with respect to age, gender, penetrating mechanism of injury, admission lactate, ISS, suture line failure, and admission systolic blood pressure. Both intraabdominal abscess rates (88.2% vs 29.6%, P < .001) and intraoperative PRBC transfusions (8 vs 1 units, P = .004) were higher in the combined pancreatic and colon injury group. Multivariable logistic regression identified both intraoperative PRBC transfusions (odds ratio, 1.09; 95% confidence interval, 1.04-1.15; P < .001) and concomitant pancreatic injury (odds ratio, 14.8; 95% confidence interval, 3.92-96.87; P < .001) as independent predictors of intraabdominal abscess formation. Both intraoperative PRBC transfusions and presence of concomitant pancreatic injury are independent predictors of intraabdominal abscess formation in patients with traumatic colon injuries.

Tranexamic acid reduces intraoperative red blood cell transfusion rates in craniosynostosis surgery: a 6-year retrospective analysis

Surgery for craniosynostosis in children is associated with substantial intraoperative bleeding and the need for blood transfusions. Recent studies have supported the efficacy of tranexamic acid (TXA) in reducing blood loss and transfusion requirements. The records of 72 patients under 18 months of age who had undergone 113 surgeries for non-syndromic craniosynostosis in a single institution for 6 years were retrospectively analyzed. The transfusion requirements in infants with and without TXA administration were compared. The concept of patient blood management before and after TXA implementation in practice was also examined. The rate of intraoperative packed red blood cells (PRBC) transfusion was significantly lower in the TXA than in the non-TXA group (26.7% vs. 83%, p < 0.001). The volume of intraoperatively transfused PRBC was also lower in the TXA group compared to the non-TXA group (mean 68.25 mL vs. 101.91 mL, p < 0.001), as was the weight-adjusted volume (mean 11.2 mL/kg vs. 15 mL/kg, p = 0.002). There were no significant differences in the rate and volumes of postoperative PRBC transfusion between groups. The volume of intraoperatively transfused PRBC was dependent on TXA administration, but not on the affected suture and type of intervention. We found that while in the pre-TXA period all patients were transfused intraoperatively, the frequency of intraoperative transfusions in the post-TXA period was reduced by 40.9% even in the patients who had not received TXA. TXA seems to effectively reduce the intraoperative transfusion requirements in children undergoing craniosynostosis surgery. The optimal blood management in this patient population remains to be further evaluated.

The effect of transfusion on survival in head and neck cancer after free tissue reconstruction.

To examine if perioperative blood transfusion affects overall survival (OS) and recurrence-free survival (RFS) in head and neck cancer patients who undergo free tissue reconstruction. Retrospective cohort study. The medical records of free tissue flaps between 2007 and 2010 were reviewed. Differences in demographics and clinical factors based on the level of transfused packed red blood cells (PRBC) were examined using chi-squared tests, Kruskal-Wallis tests, and/or ANOVA tests. Survival time was compared using a Cox proportional hazard model. Data were available for 183 patients. Patients who had PRBC transfusion significantly differed from the non-transfused group by flap type, flap with bone, Charlson Comorbidity Index (CCI), and hemoglobin and hematocrit. When stratified into three groups based on units of PRBC; flap type, flap with bone, CCI, preoperative hemoglobin, and hematocrit were found to differ significantly. The 2-year Kaplan-Meier plot demonstrated improved OS for those who did not receive any PRBC transfusion. The use of more than 3 units of blood decreased 2-year OS significantly when compared to the non-transfused group. Finally, after adjusting for CCI using a Cox proportional hazard model, survival was significantly affected by CCI. After controlling for patient age, oncologic stage, cancer subsite, histology, type of free flap, vascularized bone-containing flap, recurrence type, CCI, and preoperative hemoglobin and hematocrit, patients who received 3 or more units of PRBC in the perioperative period had significantly decreased OS. RFS did not differ between the transfused versus non-transfused groups. Level 4.

Iron Overload in Children with Acute Lymphoblastic and Acute Myeloblastic Leukemia-Experience of One Center.

Transfusions of packed red blood cells (PRBCs), given due to an oncological disease and its acute complications, are an indispensable part of anticancer therapy. However, they can lead to post-transfusion iron overload. The study aim was to evaluate the role of ferritin as a nonspecific marker of leukemic growth and marker of transfusion-related iron overload. We performed a longitudinal study of PRBC transfusions and changes in ferritin concentrations during the oncological treatment of 135 patients with childhood acute lymphoblastic and acute myeloblastic leukemia (ALL and AML, median age 5.62 years). At the diagnosis, 41% of patients had a ferritin level over 500 ng/mL, and 14% of patients had a ferritin level over 1000 ng/mL. At the cessation of the treatment, 80% of the children had serum ferritin (SF) over 500 ng/mL, and 31% had SF over 1000 ng/mL. There was no significant difference between SF at the beginning of the treatment between ALL and AML patients, but children with AML finished treatment with statistically higher SF. AML patients had also statistically higher number of transfusions. We found statistically significant positive correlations between ferritin and age, and weight and units of transfused blood. Serum ferritin at the moment of diagnosis can be a useful marker of leukemic growth, but high levels of SF are connected with iron overload in both AML and ALL.

Red Blood Cell Transfusion and Pulmonary Complications: The Society of Thoracic Surgeons Adult Cardiac Surgery Database Analysis

BackgroundIntraoperative packed red blood cell (PRBC) transfusion during cardiac surgery is associated with increased postoperative morbidity and mortality; however, data on the association between PRBC transfusion and postoperative pulmonary complications (PPCs) are somewhat conflicting. Using The Society of Thoracic Surgeons Adult Cardiac Surgery Database, we sought to determine whether intraoperative PRBC transfusion was associated with PPCs as well as with longer intensive care unit (ICU) stay after isolated coronary artery bypass grafting (CABG) surgery. MethodsA registry-based cohort study was performed on 751,893 patients with isolated CABG between January 1, 2015, to December 31, 2019. Using propensity score–weighted regression analysis, we analyzed the effect of intraoperative PRBC on the incidence of PPCs (hospital-acquired pneumonia [HAP], mechanical ventilation for >24 hours, or reintubation), ICU length of stay, and ICU readmission. ResultsTransfusion of 1, 2, 3, and ≥4 units of PRBCs was associated with increased odds for HAP (odds ratios [ORs], 1.24 [95% CI, 1.21-1.26], 1.28 [95% CI, 1.26-1.32], 1.36 [95% CI, 1.33-1.39], 1.31 [95% CI, 1.28-1.34]), reintubation (ORs, 1.23 [95% CI, 1.21-1.25], 1.38 [95% CI, 1.35-1.40], 1.57 [95% CI, 1.55-1.60], 1.70 [95% CI, 1.67-1.73]), prolonged ventilation (ORs, 1.34 [95% CI, 1.33-1.36], 1.56 [95% CI, 1.53-1.58], 1.97 [95% CI, 1.94-2.00], 2.27 [95% CI, 2.24-2.30]), initial ICU length of stay (mean difference in hours, 6.79 [95% CI, 6.00-7.58], 9.55 [95% CI, 8.71-10.38], 17.26 [95% CI, 16.38-18.15], 22.14 [95% CI, 21.22-23.06]), readmission to ICU (ORs, 1.14 [95% CI, 1.12-1.64], 1.15 [95% CI, 1.12-1.17], 1.15 [95% CI, 1.13-1.18], 1.32 [95% CI, 1.29-1.35]), and additional ICU length of stay (mean difference in hours, 0.55 [95% CI, 0.18-0.92], 0.38 [95% CI, 0.00-0.77], 1.02 [95% CI, 0.61-1.43], 1.83 [95% CI, 1.40-2.26]), respectively. ConclusionsIntraoperative PRBC transfusion was associated with increased incidence of PPCs, prolonged ICU stay, and ICU readmissions after isolated CABG surgery.

Red blood cell transfusion-related dynamics of extracellular vesicles in intensive care patients: a prospective subanalysis

Extracellular vesicles (EVs) accumulate during packed red blood cell (PRBC) storage. To date, the involvement of EVs in transfusion-related immunomodulation (TRIM) has not been prospectively evaluated in intensive care unit (ICU) patients. This was a prospective subanalysis of a recent observational feasibility study in postoperative ICU patients after: (1) open aortic surgery (Aorta), (2) bilateral lung transplantation (LuTx), and (3) other types of surgery (Comparison). Patient plasma was collected three times each before and after leukoreduced PRBC transfusion at 30-min intervals. The total number of EVs and EVs derived from erythrocytes (EryEVs), total platelets (total PEVs), activated platelets, granulocytes (GEVs), monocytes, and myeloid cells in PRBC samples and patient plasma were analyzed by flow cytometry. Statistical analysis was performed by Spearman’s correlation test, linear mixed models and pairwise comparisons by Wilcoxon matched-pairs test. Twenty-three patients (Aorta n = 5, LuTx n = 9, Comparison n = 9) were included in the final analysis. All EV subgroups analyzed were detectable in all PRBCs samples (n = 23), but concentrations did not correlate with storage time. Moreover, all EVs analyzed were detectable in all plasma samples (n = 138), and EV counts were consistent before transfusion. Concentrations of total EVs, EryEVs, total PEVs, and GEVs increased after transfusion compared with baseline in the entire cohort but not in specific study groups. Furthermore, the change in plasma EV counts (total EVs and EryEVs) after transfusion correlated with PRBC storage time in the entire cohort. Extracellular vesicles were detectable in all PRBC and plasma samples. Individual EV subtypes increased after transfusion in the entire cohort, and in part correlated with storage duration. Future clinical studies to investigate the role of EVs in TRIM are warranted and should anticipate a larger sample size.Trial registration: Clinicaltrials.gov: NCT03782623.

Early Treatment of Acetabular Fractures via an Anterior Approach Increases Blood Loss but not Packed Red Blood Cell Transfusion.

To determine if time from hospital admission to surgery for acetabular fractures using an anterior intrapelvic (AIP) approach affected blood loss. Multicenter retrospective study. Three level 1 trauma centers at 2 academic institutions. 195 adult (age >18) patients with adequate records to complete analysis and no pre-existing coagulopathy. AIP approach without other significant same day procedures (irrigation and debridement and external fixation were the only other allowed procedures). Multiple methods for evaluating blood loss were investigated, including estimated blood loss (EBL), calculated blood loss (CBL), and packed red blood cell (PRBC) transfusion requirement. On continuous linear analysis, increasing time from admission to surgery was significantly associated with decreasing CBL at 24 hours (-1.45 mL per hour by Gross, p=0.003; -0.440 g of Hgb per hour by Hgb balance, p=0.003) and 3 days (-1.69 mL per hour by Gross, p=0.013; -0.497 g of Hgb per hour by Hgb balance, p=0.010) postoperative, but not EBL or PRBC transfusion. Using 48-hours from admission to surgery to define early versus delayed, blood loss was significantly greater in the early group compared to delayed [453 (IQR 277-733) mL early versus 364 (IQR 160-661) delayed by Gross, p=0.017; 165 (IQR 99-249) g early versus 143 (IQR 55-238) g delayed by Hgb balance, p=0.035], but not EBL or PRBC transfusion. Additionally, in multivariate linear regression, neither giving tranexamic acid nor administering prophylactic anticoagulation for venous thromboembolism on the morning of surgery affected blood loss at 24 hours or 3 days postoperative. There is higher blood loss with early surgery using an AIP approach, but early surgery did not affect PRBC transfusion and may not be clinically relevant. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Effectiveness of zinc protoporphyrin/heme ratio and ferritin for assessing iron status in preterm infants.

Since iron is crucial for many tissue processes, we, therefore, aimed to assess ferritin and the zinc protoporphyrin to heme ratio (ZnPP/H) as indicators of iron status in preterm newborns, particularly during certain inflammatory episodes. From 170 preterm babies, paired ferritin and ZnPP/H measurements were collected twice (on the first postnatal day and six weeks later). To compare these measures and assess the impact of anemia, sepsis, and packed red blood cell transfusion (PRBT), three different scenarios were considered. Compared to the non-anemic group, the anemic patients' serum ferritin level was considerably lower (p = 0.044), whereas the anemic patients' ZPP/H ratio was significantly greater (p < 0.001). In neonates with sepsis, ferritin levels were considerably greater in both anemic and non-anemic septic neonates compared to neonates without sepsis (p < 0.001 for each). Regarding ZPP/H ratio, no appreciable variations were found between the two groups. In addition, serum ferritin significantly increased following each PRBT (p < 0.001 for each). As a result of each PRBT, the ZPP/H ratio considerably decreased (p < 0.001). As a measure of iron status during particular inflammatory processes like infection and PRBT, ZnPP/H may be more accurate.

Abnormal Iron Status and Adverse Outcome After Elective Cardiac Surgery: A Prospective, Observational Multicenter Study

ObjectivesTo investigate the incidence of preoperative abnormal iron status and its association with packed red blood cell (PRBC) transfusion, postoperative major complications, and new onset of clinically significant disability in patients undergoing elective cardiac surgery. DesignProspective, observational multicenter cohort study. SettingThree heart surgical centers in the Netherlands, between 2019 and 2021. Recruitment was on hold between March and May 2020, due to COVID-19. Patients427 patients aged 60 years and older who underwent elective on-pump cardiac surgery. Measurements and Main ResultsPrimary endpoint was 30-day packed red blood cell (PRBC) transfusion. Secondary endpoints were postoperative major complications within 30 days (e.g., acute kidney injury, sepsis), and new onset of clinically significant disability within 120 days within surgery. Iron status was evaluated prior to surgery. An abnormal iron status was present in 45.2% of patients (n=193), and most frequently the result of iron deficiency (27.4%, n = 117). An abnormal iron status was not associated with PRBC transfusion (adjusted relative risk (ARR) 1.2; 95% confidence interval (95% CI) 0.9 to 1.8: p = 0.227) or new onset of clinically significant disability (ARR 2.0; 95% CI 0.9 to 4.6: p = 0.098). However, the risk of postoperative major complications was increased in patients with an abnormal iron status (ARR 1.7; 95% CI 1.1 to 2.5: p = 0.012). ConclusionsAn abnormal iron status prior to elective cardiac surgery was associated with an increased risk of postoperative major complications, but not with PRBC-transfusion or new onset of clinically significant disability.

Placenta Accreta Spectrum Disorders - The Impact of the Creation of a Multidisciplinary Team on Maternal Outcomes in Portugal.

To describe a cohort of placenta accreta spectrum (PAS) cases from a tertiary care institution and compare the maternal outcomes before and after the creation of a multidisciplinary team (MDT). Retrospective study using hospital databases. Identification of PAS cases with pathological confirmation between 2010 and 2021. Division in two groups: standard care (SC) group - 2010-2014; and MDT group - 2015-2021. Descriptive analysis of their characteristics and maternal outcomes. During the study period, there were 53 cases of PAS (24 - SC group; 29 - MDT group). Standard care group: 1 placenta increta and 3 percreta; 12.5% (3/24) had antenatal suspicion; 4 cases had a peripartum hysterectomy - one planned due to antenatal suspicion of PAS; 3 due to postpartum hemorrhage. Mean estimated blood loss (EBL) was 2,469 mL; transfusion of packed red blood cells (PRBC) in 25% (6/24) - median 7.5 units. Multidisciplinary team group: 4 cases of placenta increta and 3 percreta. The rate of antenatal suspicion was 24.1% (7/29); 9 hysterectomies were performed, 7 planned due to antenatal suspicion of PAS, 1 after intrapartum diagnosis of PAS and 1 after uterine rupture following a second trimester termination of pregnancy. The mean EBL was 1,250 mL, with transfusion of PRBC in 37.9% (11/29) - median 2 units. After the creation of the MDT, there was a reduction in the mean EBL and in the median number of PRBC units transfused, despite the higher number of invasive PAS disorders.

Time of Attainment of Clinical Remission and Peripheral Blood Count Recovery during Induction Chemotherapy for Childhood Acute Lymphoblastic Leukemia

Background: Acute lymphoblastic leukemia(ALL) is the most common pediatric malignancy. Infection and bleeding are the leading cause of death during induction chemotherapy in childhood ALL. So, proper knowledge about anticipated infection and bleeding are very important during this period. But the duration of clinical remission and recovery of peripheral blood count during induction chemotherapy is not well reported in literature. Objective: The aim of the study was to determine the time of attainment of clinical remission and recovery of peripheral blood count after initiation of induction chemotherapy and to determine if the duration of clinical remission and peripheral blood count recovery differs between therapeutic risk groups. Methods: This prospective observational study was conducted from January 2021 to December 2021 in the Department of Paediatric Haematology and Oncology, BSMMU. Newly diagnosed admitted Eighty-Six ALL of both sexes aged 1 to 17.9 years were included. After commencing chemotherapy, physical examination was recorded every day until clinical remission and complete blood count (CBC) was recorded one to two days interval until peripheral blood count recovery. The number of packed red blood cell (PRBC) and platelet transfusions and the number of days of intravenous antibiotics were recorded. Results: Mean duration of clinical remission, complete Hemoglobin (Hb), Absolute neutrophil count(ANC) and platelet recovery was 8.4 ± 4.5 days, 25±7.9 days, 23.3±5.6 days and 21.8±6.4 days respectively (p&lt;0.01). Time to attain partial recovery of platelet was 14.0±4.9 days in high risk and 19.2±5.3 days in standard risk group. PRBC transfusion requirement was 2.2±1.2 units in high risk group and 1.7±0.8 units in standard risk group (p&lt;0.05). Time to attain partial recovery of ANC, number of days with I/V antibiotics and duration of treatment interruption were higher in high risk group. Conclusion: Time of clinical remission was similar between risk group. Platelet recovery occurred earlier than Hemoglobin (Hb) and absolute neutrophil count (ANC) recovery. Transfusion and supportive care requirement were more in high risk group during induction chemotherapy. So, more supportive care should be arranged up to three weeks of induction period to increase survival of high risk childhood ALL. Bangladesh Med Res Counc Bull 2023; 49: 177-182

Sustained Efficacy, Safety, and Improved Quality of Life in Adult and Pediatric Patients with Transfusion-Dependent β-Thalassemia up to 9 Years Post Treatment with Betibeglogene Autotemcel (Beti-cel)

Introduction: Beti-cel gene therapy addresses the underlying cause of transfusion-dependent β-thalassemia (TDT) by adding functional copies of a modified β-globin gene to autologous CD34+ hematopoietic stem and progenitor cells (HSPCs) via a third-generation, self-inactivating lentiviral vector (LVV), BB305, which produces functional adult hemoglobin (Hb), HbA T87Q, in red blood cells (RBCs). Here, we report efficacy, safety, and quality of life (QOL) data from adult and pediatric patients treated with beti-cel who were followed for up to 9 years after treatment. These outcomes may inform patient selection for real-world treatment with beti-cel. Methods: Patients with TDT who completed either a phase 1/2 (HGB-204 [NCT01745120]; HGB-205 [NCT02151526]) or phase 3 (HGB-207 [NCT02906202]; HGB-212 [NCT03207009]) beti-cel parent study and subsequently participated in the long-term, 13-year follow-up study LTF-303 (NCT02633943) were included in this analysis. Analyses were performed with data collected through January 30, 2023. Efficacy (including transfusion independence [TI], defined as a weighted average Hb ≥9 g/dL without packed RBC transfusions for ≥12 months) and safety are reported through last follow-up. QOL data are reported for studies HGB-204, HGB-207, and HGB-212 through month 36. Statistical analyses were conducted to examine key outcomes in subgroups based on patient age at enrollment (pediatric: &amp;lt;18 years; adult: ≥18 years). Results:As of January 30, 2023, 63 patients (median [range] age: 17 [4-35] years) had received beti-cel in a phase 1/2 or 3 study and enrolled in LTF-303, with a median (range) follow-up of 60.1 (23.8-109.5) months. Phase 3 studies used the commercial drug product manufacturing process. Ninety percent (37/41) of phase 3 patients achieved and maintained TI through last follow-up (up to 6 years; Table 1). TI rates by study, genotype, and age for phase 3 patients are also presented in Table 1. In phase 1/2 studies that used an older drug manufacturing process, 68.2% (15/22) of patients achieved TI; 14 of these patients sustained TI through last follow-up (up to 9 years). One patient no longer meets protocol-defined TI as a result of Hb level &amp;lt;9g/dL at year 6 due to acute health events unrelated to β-thalassemia, which were not attributed to loss of beti-cel treatment effect. Approximately 80% of pediatric and adult patients required only one mobilization cycle to achieve the drug product dose. The median percentage of drug product cells transduced with the BB305 LVV was comparable between adult and pediatric populations (78% and 80%, respectively), as were the month 6 median peripheral blood vector copy number (1.4 c/dg and 1.1 c/dg) and HbA T87Q (9.4 g/dL and 8.3 g/dL). Adult patients reported improvements in QOL up to month 36 as assessed by the Short Form-36 Health Survey Questionnaire mental and physical component summary scores, Functional Assessment of Cancer Therapy, and EuroQol ( Table 2). Pediatric Quality of Life Inventory scores will be reported at the time of presentation. Overall, 19% (12/63) of patients experienced ≥1 beti-cel-related adverse event (AE); the most common beti-cel-related AEs (occurring in ≥3 patients) were abdominal pain (experienced in 5/63 [7.9%] patients) and thrombocytopenia (3/63 [4.8%] patients). Five patients experienced serious veno-occlusive liver disease; all 5 received defibrotide and recovered. No malignancies, insertional oncogenesis, or vector-derived replication-competent lentivirus were reported. Age subgroup safety analysis as of last follow-up will be reported in the final presentation. Conclusion: Beti-cel is a potentially curative gene therapy for patients with TDT across ages and genotypes through achievement of TI and normal or near-normal Hb. These data will inform real-world beti-cel treatment decisions for patients with TDT and providers.

AsCas12a Gene Editing of HBG1/2 Promoters with EDIT-301 Results in Rapid and Sustained Normalization of Hemoglobin and Increased Fetal Hemoglobin in Patients with Severe Sickle Cell Disease and Transfusion-Dependent Beta-Thalassemia

Background: Sickle cell disease (SCD) and transfusion-dependent β-thalassemia (TDT) are hereditary blood disorders caused by mutations in the β-globin gene. Clinical evidence has demonstrated that increased fetal hemoglobin (HbF, α2γ2) can reduce or eliminate SCD and TDT complications. EDIT-301, an investigational gene-edited autologous hematopoietic stem cell medicine, has a unique genomic modification that mimics naturally occurring mutations of hereditary persistence of fetal hemoglobin in the γ-globin gene ( HBG1/2) promoters. These mutations reactivate γ-globin expression and increase HbF production. EDIT-301 is manufactured with a highly efficient and specific, proprietary gene editing nuclease, AsCas12a. In preclinical studies, edited CD34 + cells from patients with SCD or TDT increased HbF production in red blood cells (RBCs) sufficient for a therapeutic effect, including reduced sickling (SCD) and improved erythropoiesis (TDT). Aim: RUBY (NCT04853576) and EdiThal (NCT05444894) are Phase I/II, multicenter, open-label, single-arm studies evaluating the safety, efficacy, and tolerability of EDIT-301 in patients with severe SCD and TDT, respectively. As of June 28, 2023, 7 SCD patients and 2 TDT patients have received EDIT-301 treatment. Preliminary clinical efficacy and safety data are reported. Methods: Patients aged 18-50 years with severe SCD (defined as ≥2 severe vaso-occlusive events [VOEs] per year in the 2 years prior to informed consent [IC]) and patients aged 18-35 years with TDT (defined as at least 100 mL/kg/year or 10 U/year of packed RBC transfusions in the 2 years prior to IC) were eligible to enroll in RUBY and EdiThal, respectively. Autologous CD34 + hematopoietic stem and progenitor cells collected by apheresis after plerixafor (RUBY) or plerixafor + filgrastim (EdiThal) mobilization were edited at the HBG1/2 promoters with AsCas12a. After myeloablative conditioning with busulfan, patients received a single infusion of EDIT-301 (a minimum of 3 × 10 6 CD34 + cells/kg), and were monitored for engraftment, total hemoglobin (Hb), HbF, mean HbF concentration/F-cell (MCH-F/F-cell), percentage of F-cells, markers of hemolysis, transfusion requirement, VOEs (SCD only), and adverse events (AEs) for 24 months. Results: Based on a data cut of June 28, 2023, Patients 1-4 with SCD were 12-, 9-, 4-, and 4-months post-EDIT-301 infusion, respectively. Patients 5-7 with SCD were &amp;lt;1-month post-EDIT-301 infusion. Patients 1-2 with TDT were 3- and &amp;lt;1-months post-EDIT-301 infusion, respectively. Neutrophil and platelet engraftment were achieved after a mean (range) of 25 (23-29) and 27 (19-37) days in Patients 1-4 with SCD and on Day 23 and 26 in Patient 1 with TDT, respectively. There were no VOEs in SCD patients post-EDIT-301 infusion, compared with a mean (range) of 4.2 (3.0-5.5) VOEs/year in the 2 years before enrollment (n=6). Following EDIT-301 infusion, Hb levels rapidly increased to 14.2 (12.4-15.7) g/dL by Month 4 (n=4), reaching the normal physiological range, from a mean (range) of 10.5 (8.5-11.9) g/dL at baseline (n=5). By Month 4, the mean (range) HbF concentration was 6.8 (5.7-7.6) g/dL and HbF was &amp;gt;40% (n=4); Patients 3 and 4 had &amp;gt;50% HbF. Percentage of F-cells and MCH-F/F-cell also increased. Key markers of hemolysis improved or normalized in all patients with SCD. Patient 1 with TDT had a HbF concentration of 7.2 g/dL by Month 3, stopped receiving RBC transfusions 20 days after EDIT-301 infusion, and remained transfusion free through the 3-month period. Patient 2 with TDT also showed early improvements. The safety profile of EDIT-301 in both SCD and TDT was consistent with myeloablative conditioning with busulfan. No serious AEs were reported after EDIT-301 infusion. Conclusion: These data demonstrated successful engraftment, a rapid and sustained normalization of Hb as early as 4 months after infusion, an increase in HbF and percentage of F-cells, resolution of VOEs (SCD) and transfusion independence (TDT). In addition, there were improvements in key markers of hemolysis (SCD) and a favorable safety profile in EDIT-301-treated patients. EDIT-301 treatment showed promising results for the first clinical use of AsCas12a in both SCD and TDT patients after gene editing of the γ-globin gene ( HBG1/2) promoters. These findings support further investigation of EDIT-301 in the RUBY and EdiThal trials. Updated data with additional outcomes will be presented.

Improvements in Health-Related Quality of Life after Exagamglogene Autotemcel in Patients with Transfusion-Dependent Beta-Thalassemia

Background: Transfusion-dependent β-thalassemia (TDT), an inherited hematological disorder which requires life-long, chronic red blood cell transfusion (RBC) and regular iron chelation therapy, has a substantial negative impact on health-related qualify of life (HRQoL). Exagamglogene autotemcel (exa-cel) is a one-time, non-viral, ex vivo CRISPR-Cas9 gene-edited cell therapy in phase 3 clinical trials that has been shown to eliminate the need for RBC transfusions and achieve transfusion independence. Here, we report HRQoL data from a pre-specified interim analysis of the exa-cel CLIMB TDT-111 study. Methods: CLIMB TDT-111 is an ongoing, 24-mo, phase 3 trial of a single dose of exa-cel in patients aged 12-35 years with TDT and a history of ≥100 mL/kg/year or ≥10 U/year of packed RBC transfusions for 2 years prior to screening. Changes in patient-reported outcome (PRO) measures including EuroQol Quality of Life Scale 5 dimensions 5 levels of severity (EQ-5D-5L, including descriptive system and visual analog scale [VAS]) and Functional Assessment of Cancer Therapy Bone Marrow Transplant (FACT-BMT, including FACT-General [FACT-G] and bone marrow transplant subscale [BMTS]) for adults and the EuroQol Quality of Life Scale 5 dimensions youth (EQ-5D-Y) and Pediatric Quality of Life Inventory (PedsQL) for adolescents were assessed through month 24 as a secondary endpoint in the trial. Data are presented as of 16 January 2023 for the 24 adults (aged ≥18-35 years) and 11 adolescents (aged ≥12 to &amp;lt; 18 years) who had been followed for ≥16 months after exa-cel infusion. Results: Clinically meaningful improvements, exceeding the minimal clinically important difference (MCID) thresholds, were observed in all PRO measures in adults. Baseline mean EQ-5D-5L health utility US index score (n=24, mean [SD]: 0.85 [0.18]) was near the general population norm and in line with baseline scores previously reported for adult patients with TDT. By month 24, both EQ-5D-5L health utility US index scores and EQ VAS scores showed substantial improvement (mean [SD] changes at month 24 [n=15]: 0.12 [0.26] and 10.2 [20.9] points; MCIDs 0.078 and 7 to 10, respectively). FACT-G Total Score improved from baseline by month 12 and was sustained through month 24 (mean [SD] change at month 24 [n=15] 10.3 [17.0] points; MCID 3 to 7), with improvements observed in all 4 subscales (physical, social/family, emotional, and functional well-being). BMTS score improved by month 12 and was sustained through month 24 (mean [SD] change at month 24 [n=15] 6.8 [4.7] points; MCID 2 to 3). For adolescents, EQ VAS scores improved through month 18 (mean [SD] change from baseline 4.8 [6.1] points). Total PedsQL score improved by month 6 and was sustained through month 18 (mean [SD] change from baseline [n=7] 14.1 [9.2] points; MCID 4.36). Physical functioning and psychosocial health scores, sub-components of PedsQL, both showed sustained improvement through month 18 (mean [SD] change [n=7] 19.2 [9.1] and 11.4 [10.9] points; MCID of 6.66 and 5.30 points, respectively). Improvement in psychosocial score was observed in all 3 subscales (social, emotional, and school functioning). Conclusion: Adults and adolescents infused with exa-cel reported sustained and clinically meaningful improvements in their HRQoL, with improvements observed across different instruments and domains, including physical, emotional, social/family and functional well-being and overall health status. These results demonstrate the broad clinical benefits of exa-cel in patients with TDT.

The impact of red blood cell transfusion in preterm neonates on germinal matrix hemorrhage: incidence and grade with correlation to outcome

BackgroundGerminal matrix hemorrhage affects 20 to 25% of infants with a low birth weight (less than 1500 g). About one-tenth of them progress to intra-parenchymal hemorrhage, usually during the first days after birth. Several studies have found a correlation between packed RBC transfusions and a higher frequency of severe germinal matrix hemorrhage in neonatal intensive care units.Transcranial ultrasound is a safe, noninvasive modality that can be used repeatedly in the neonates with ability to detect different grades of germinal matrix hemorrhage.ObjectiveWas to evaluate the impact of packed RBC transfusion on the incidence and grade of germinal matrix hemorrhage, as evaluated by transcranial Doppler, and correlation to outcome.MethodsThis prospective observational study included one hundred preterm infants admitted to NICU, suffering from GM hemorrhage throughout 9 months duration. Bedside transcranial ultrasound was done for all the patients with a correlation of the grade of hemorrhage to the onset of blood transfusion, different clinical parameters, and the outcome.ResultsStatistical analysis showed a significant relation between the age of the first PRBC transfusion and GM hemorrhage grade. A positive relation was found between total amounts of PRBC transfusion and increasing grade of GM hemorrhage. A negative relation was found between GM hge grades and Apgar scores. GM hge patients who received PRBC transfusion had lower mean birth weight, lower gestational age, and longer duration of hospital stay than those who have not received PRBC transfusion.ConclusionClose monitoring of preterm neonates receiving packed RBCs, by transcranial ultrasound, as early as possible, is mandatory to early detect GM hge and limit subsequent morbidities.

Unraveling Leukocyte Profile Shifts and Platelet Dynamics Following Leukoreduced Packed Red Cell Transfusions in Very Low Birth Weight Preterm Neonates.

Background Packed red blood cell (PRBC) transfusions are routine in neonatal care and the most common blood product administered to sick neonates. However, their impact on leukocyte and platelet profiles in very low birth weight (VLBW) preterm infants remains largely unexplored.This study examines leukocyte profile shifts and platelet dynamics following leukoreduced PRBC transfusions in VLBW preterm infants, offering insights to improve neonatal care and reduce unnecessary interventions. Methods The study utilized a retrospective cohort design within a single center, focusing on VLBW preterm infants who received PRBC transfusions at a level 3 NICU between January 2014 and June 2019. Data collection encompassed white blood cell (WBC) and platelet count measurements taken 24 hours before and up to 72 hours after PRBC transfusion. Neonates lacking complete blood count (CBC) data within the 72-hour post-transfusion window were excluded. A subgroup analysis distinguished the outcome between the initial PRBC transfusion and subsequent ones. The statistical significance of pre- and post-transfusion laboratory data was determined using the Wilcoxon signed ranks test and paired T-test. Results A cohort of 108 VLBW preterm infants who underwent a total of 402 PRBC transfusions was included in the analysis. The subjects exhibited a mean gestational age of 27.2 ± 2.5 weeks and a mean birth weight of 913 ± 264 grams. Analysis of pre- and post-transfusion data revealed no significant differences in total white blood cell count (WBC), absolute neutrophil count (ANC), absolute monocyte count (AMC), absolute eosinophil count, and absolute lymphocyte count. Notably, the platelet count was significantly decreased in the post-transfusion group (p < 0.001). In a subset analysis limited to the first-time transfusions among the 108 infants, a statistically significant increase was observed in total WBC, AMC, and ANC following transfusion. Conclusions The findings of this study highlight that PRBC transfusions can prompt an increase in neutrophils, monocytes, and eosinophils, coupled with a decline in platelet counts, all within a 72-hour window post-transfusion. Notably, these changes were predominantly discernible after the initial transfusion, with subsequent transfusions demonstrating consistency, except for the observed platelet count reduction. Recognizing these patterns could prove instrumental in averting undue investigations for suspected sepsis, particularly following the initial transfusion event. However, further in-depth investigations are necessary to uncover the underlying factors responsible for the shifts in leukocyte and platelet profiles triggered by PRBC transfusions.

Real-World Presentation and Prognostic Effect of Allogeneic Blood Transfusion during the Intensive Induction Phase in Pediatric Acute Lymphoblastic Leukemia.

Purpose: To determine associations between allogeneic blood transfusion (ABT) during the intensive induction phase of therapy and prognostic effect in a real-world cohort of pediatric patients with acute lymphoblastic leukemia (ALL). Methods: A total of 749 pediatric patients who were diagnosed with ALL were enrolled in this study by using a single-center retrospective cohort study method from February 2008 to May 2022. Results: Among the ABT patients, 711 (94.9%) children were transfused with packed red blood cells (PRBCs), 434 (57.9%) with single-donor platelets (SDPs), and 196 (26.2%) with fresh frozen plasma (FFP). Our multivariate analysis demonstrated that FFP transfusion was the unique independent factor that affected both relapse-free survival (RFS) and overall survival (OS). The transfusion of FFP was significantly associated with higher age (p < 0.001), being more likely to receive SCCLG-ALL-2016 protocol (p < 0.001), higher proportion of more than 25 blood product transfusions, more PRBC transfusion (p < 0.001), and higher D33-MRD-positive rates (p = 0.013). Generalized additive models and threshold effect analysis using piece-wise linear regression were applied to identify the cut-off value of 25 mL/kg for average FFP transfusion. K-M survival analysis further confirmed that average FFP transfusion > 25 mL/kg was an independent adverse indicator of inferior outcome in terms of RFS (p = 0.027) and OS (p = 0.033). Conclusions: In blood products, only FFP supplement is closely related to the prognosis of childhood ALL. During the intensive induction phase, the indications of FFP transfusion should be strictly grasped, and the total amount of FFP should be controlled and kept below 25 mL/kg.

Efficacy of the Hepcon system in reducing hemorrhagic and thrombotic complications in antiphospholipid syndrome patients undergoing cardiac surgery.

Patients with Antiphospholipid Syndrome (APS) undergoing cardiopulmonary bypass (CPB) surgery are at increased risk for thrombotic and hemorrhagic complications. Anticoagulation during CPB is typically monitored with activated clotting time (ACT) which may be falsely prolonged in patients with APS. The Hepcon Hemostasis Management System quantitatively determines the whole blood heparin concentration through heparin/protamine titration. This was a retrospective study of APS patients who underwent cardiac surgery requiring CPB at the Cleveland Clinic between April 2013, and July 2020. The primary endpoint was the composite rate of hemorrhagic or thromboembolic complications per surgical case in patients monitored by Hepcon versus patients monitored by ACT. Secondary endpoints were median volume of chest tube output and packed red blood cell (PRBC) transfusion within the first three post-operative days. 43 patients were included. 20 (47%) patients were monitored using Hepcon while 23 (53%) were monitored using ACT. For the primary endpoint of rate of thromboembolic or hemorrhagic complications per surgical case, there was no statistically significant difference between the Hepcon and ACT groups (HMS, 6/20 [30%]; ACT, 7/23 [30%]; p = >0.99). For the secondary endpoints, there was no statistically significant difference in median post-operative chest tube output (780mL vs. 850mL; p = 0.88) and median post-operative PRBC transfusion (1 unit vs. 0 unit; p = 0.28) between the Hepcon and ACT groups, respectively. There was no difference in the composite outcome of thrombotic or hemorrhagic complications in patients monitored by Hepcon versus those monitored by ACT.

In hospitalized patients undergoing therapeutic plasma exchange, major bleeding prevalence depends on the bleeding definition: An analysis of The Recipient Epidemiology and Donor Evaluation Study-III.

Major bleeding in patients undergoing therapeutic plasma exchange (TPE) has been studied in large databases; but without standardizing bleeding definitions. Therefore, we used standardized definitions to evaluate major bleeding in hospitalized patients undergoing TPE using public use data files from the Recipient Epidemiology and Donor Evaluation Study-III (REDS-III). In a retrospective cross-sectional analysis, we identified TPE-treated adults in a first inpatient encounter. We evaluated major bleeding prevalence using (1) International Classification of Diseases (ICD) or Current Procedural Terminology (CPT) codes, (2) packed red blood cell (PRBC) transfusion, or (3) hemoglobin (Hgb) decline. Patients with major bleeding prior to their first TPE were excluded from the analysis. Among 779 patients undergoing TPE, major bleeding by at least one of the three bleeding definitions occurred in 135 patients (17.3%). For each of the ICD/CPT, PRBC, and Hgb definitions, the prevalence of major bleeding was 2.8% (n = 31), 7.4% (n = 81), and 5.4% (n = 59), respectively. Only 3.7% of bleeds (5/135) were captured by all three definitions and 19.3% (26/135) exclusively by any two pairwise definitions. The addition of PRBC transfusion and Hgb decline to ICD/CPT code definitions increased bleeding prevalence threefold. Among hospitalized adults undergoing TPE in the REDS-III study, the prevalence of major bleeding was 17.3%. The addition of PRBC and Hgb decline to ICD codes increased bleeding prevalence threefold. Future studies are needed to develop validated models that identify patients at risk for major bleeding during TPE.

Red cell transfusions in children with thalassemia: Outcomes of a10mL/kg/h infusion rate.

Children with transfusion-dependent thalassemia have an impaired ability to synthesize alpha or beta globin, which results in anemia. Packed red blood cell (PRBC) transfusions are required to increase hemoglobin, which supports appropriate growth and development. PRBC transfusions must be completed within 4h; however, infusion rates vary across institutions. Our institution infuses PRBCs up to 10mL/kg/h. A descriptive study of 21 children who received a total of 276 transfusions during 2021 demonstrated that this rate is safe and well tolerated. Shorter transfusion times support patients' and families' time, resources, and quality of life and aptly utilize institutional resources.