Red Blood Cell Transfusion Therapy Research Articles

Limited access to transcranial Doppler screening and stroke prevention for children with sickle cell disease in Europe: Results of a multinational EuroBloodNet survey.

Ensuring equitable access to adequate standard of care for patients with rare hematological disease is one of the aims of the European Reference Network (ERN) EuroBloodNet. Stroke is one of the most devastating complications for children with sickle cell disease (SCD). For effective prevention of stroke risk, annual transcranial Doppler (TCD) according to a defined protocol is recommended for patients aged 2-16years, with red blood cell transfusion therapy for those at risk. There is no information regarding screening for stroke risk and stroke prevention programs in Europe. Seven SCD experts of five healthcare providers (HCPs) of ERN EuroBloodNet developed an online survey to assess the access to TCD screening and stroke prevention programs for children with SCD in Europe. Eighty-one experts in 77 HCPs from 16 European countries responded to 16 online questions. Thirty-two of 77 (51%) HCPs were EuroBloodNet reference centers, and 36% physicians reported not having a dedicated TCD/TCD imaging service for children with SCD. Only 30% of physicians provided estimates that all their patients received annual TCD according to the standard protocol due to lack of trained staff (43%), lack of TCD instruments (11%), refusal of patients due to logistical difficulties (22%), and lack of funds for dedicated staff or equipment (11%). This multinational European survey provides the first comprehensive picture of access to TCD screening and stroke prevention in European countries. Identifying the potential underlying causes of the lack of effective standardized screening, this survey also addresses possible dedicated actions to cover these needs.

Limited access to transcranial Doppler screening and stroke prevention for children with sickle cell disease in Europe: Results of a multinational EuroBloodNet survey.

Ensuring equitable access to adequate standard of care for patients with rare hematological disease is one of the aims of the European Reference Network (ERN) EuroBloodNet. Stroke is one of the most devastating complications for children with sickle cell disease (SCD). For effective prevention of stroke risk, annual transcranial Doppler (TCD) according to a defined protocol is recommended for patients aged 2-16years, with red blood cell transfusion therapy for those at risk. There is no information regarding screening for stroke risk and stroke prevention programs in Europe. Seven SCD experts of five healthcare providers (HCPs) of ERN EuroBloodNet developed an online survey to assess the access to TCD screening and stroke prevention programs for children with SCD in Europe. Eighty-one experts in 77 HCPs from 16 European countries responded to 16 online questions. Thirty-two of 77 (51%) HCPs were EuroBloodNet reference centers, and 36% physicians reported not having a dedicated TCD/TCD imaging service for children with SCD. Only 30% of physicians provided estimates that all their patients received annual TCD according to the standard protocol due to lack of trained staff (43%), lack of TCD instruments (11%), refusal of patients due to logistical difficulties (22%), and lack of funds for dedicated staff or equipment (11%). This multinational European survey provides the first comprehensive picture of access to TCD screening and stroke prevention in European countries. Identifying the potential underlying causes of the lack of effective standardized screening, this survey also addresses possible dedicated actions to cover these needs.

Peripheral perfusion index stratifies risk in patients with intraoperative anemia: A multicentre cohort study

Study objectiveEvidence for red blood cell (RBC) transfusion thresholds in the intraoperative setting is limited, and current perioperative recommendations may not correspond with individual intraoperative physiological demands. Hemodynamics relevant for the decision to transfuse may include peripheral perfusion index (PPI). The objective of this prospective study was to assess the associations of PPI and hemoglobin levels with the risk of postoperative morbidity and mortality. DesignMulticenter cohort study. SettingBispebjerg and Hvidovre University Hospitals, Copenhagen, Denmark. PatientsWe included 741 patients who underwent acute high risk abdominal surgery or hip fracture surgery. InterventionsNo interventions were carried out. MeasurementsPrincipal values collected included measurements of peripheral perfusion index and hemoglobin values. MethodsThe study was conducted using prospectively obtained data on adults who underwent emergency high-risk surgery. Subjects were categorized into high vs. low subgroups stratified by pre-defined PPI levels (PPI: > 1.5 vs. < 1.5) and Hb levels (Hb: > 9.7 g/dL vs. < 9.7 g/dL). The study assessed mortality and severe postoperative complications within 90 days. Main resultsWe included 741 patients. 90-day mortality was 21% (n = 154), frequency of severe postoperative complications was 31% (n = 231).Patients with both low PPI and low Hb had the highest adjusted odds ratio for both 90-day severe postoperative complications (2.95, [1.62–5.45]) and 90-day mortality (3.13, [1.45–7.11]).A comparison of patients with low PPI and low Hb to those with high PPI and low Hb detected significantly higher 90-day mortality risk in the low PPI and low Hb group (OR 8.6, [1.57–162.10]). ConclusionHigh PPI in acute surgical patients who also presents with anemia was associated with a significantly better outcome when compared with patients with both low PPI and anemia. PPI should therefore be further investigated as a potential parameter to guide intraoperative RBC transfusion therapy.

Impact of Red Blood Cell Transfusion on Subsequent Cardiovascular Events in Patients with Acute Heart Failure and Anemia.

Red blood cell (RBC) transfusion therapy is often performed in patients with acute heart failure (AHF) and anemia; however, its impact on subsequent cardiovascular events is unclear. We examined whether RBC transfusion influences major adverse cardiovascular events (MACE) after discharge in patients with AHF and anemia.We classified patients with AHF and anemia (nadir hemoglobin level < 10 g/dL) according to whether they received RBC transfusion during hospitalization. The endpoint was MACE (composite of all-cause death, non-fatal acute coronary syndrome/stroke, or heart failure readmission) 180 days after discharge. For survival analysis, we used propensity score matching analysis with the log-rank test. As sensitivity analysis, we performed inverse probability weighting analysis and multivariable Cox regression analysis.Among 448 patients with AHF and anemia (median age, 81 years; male, 55%), 155 received RBC transfusion and 293 did not. The transfused patients had worse clinical features than the non-transfused patients, with lower levels of nadir hemoglobin and serum albumin and a lower estimated glomerular filtration rate. In the propensity-matched cohort of 87 pairs, there was no significant difference in the MACE-free survival rate between the 2 groups (transfused, 73.8% vs. non-transfused, 65.3%; P = 0.317). This result was consistent in the inverse probability weighting analysis (transfused, 76.0% vs. non-transfused, 68.7%; P = 0.512), and RBC transfusion was not significantly associated with post-discharge MACE in the multivariable Cox regression analysis (adjusted hazard ratio: 1.468, 95% confidence interval: 0.976-2.207; P = 0.065).In conclusion, this study suggests that RBC transfusions for anemia may not improve clinical outcomes in patients with AHF.

Endocrinopathies in beta thalassemia: a narrative review.

Beta thalassemia is the most common genetic blood disorder, characterized by reduced production or complete absence of beta-globin chains. The combination of systematic red blood cell transfusion and iron chelation therapy is the most readily available supportive treatment and one that has considerably prolonged the survival of thalassemia patients. Despite this, the development of endocrine abnormalities correlated with beta thalassemia still exists and is mostly associated with iron overload, chronic anemia, and hypoxia. A multifactorial approach has been employed to investigate other factors involved in the pathogenesis of endocrinopathies, including genotype, liver disease, HCV, splenectomy, socioeconomic factors, chelation therapy, and deficiency of elements. The development of specific biomarkers for predicting endocrinopathy risk has been the subject of extensive discussion. The objective of the present narrative review is to present recent data on endocrinopathies in beta thalassemia patients, including the prevalence, the proposed pathogenetic mechanisms, the risk factors, the diagnostic methods applied, and finally the recommended treatment options.

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.

Optimizing RBC Transfusion Outcomes in Patients with Acute Illness and in the Chronic Transfusion Setting

Red blood cell (RBC) transfusion is a common clinical intervention used to treat patients with acute and chronic anemia. The decision to transfuse RBCs in the acute setting is based on several factors but current clinical studies informing optimal RBC transfusion decision making (TDM) are largely based upon hemoglobin (Hb) level. In contrast to transfusion in acute settings, chronic RBC transfusion therapy has several different purposes and is associated with distinct transfusion risks such as iron overload and RBC alloimmunization. Consequently, RBC TDM in the chronic setting requires optimizing the survival of transfused RBCs in order to reduce transfusion exposure over the lifespan of an individual and the associated transfusion complications mentioned. This review summarizes the current medical literature addressing optimal RBC-TDM in the acute and chronic transfusion settings and discusses the current gaps in knowledge which need to be prioritized in future national and international research initiatives.

RBC Transfusion Strategy in Oncological Patients with Chronic RBC Transfusion Therapy.

Red blood cell (RBC) transfusion therapy has greatly reduced mortality and morbidity in multiply transfused patients with oncological malignancies. The aim of this study was to underline the necessity of introducing a policy for extended RBC phenotyping of these patients and for the issuing of antigen-matched blood (at least for E antigen). Multivariate logistic regression analysis was used to evaluate the associations of age, gender, transfusion history, and various malignancies with the development of red cell alloimmunization. Given the results of antibody identification, we finally obtained 732 cases to be analyzed, designating them as the p group. The respiratory system (231/732; 31.6%), digestive system (273/732; 37.3%), and female reproductive system (127/732; 17.3%) had the three highest alloimmunization rates in the p group. We screened 81 cases from the p group for which antibody screening in our laboratory had historically yielded negative results. Among the 81 cases with antibody seroconversion, anti-E was the most frequently observed antibody (37%). The results related to multivariate logistic regression analysis of the Rh group indicate that, in contrast to the other variates, transfusion confers a strongly increased risk of Rh blood system-related red cell alloimmunization. To reduce alloimmunization in tumor patients, it will be essential to introduce a policy for extended RBC phenotyping of high-risk patients and for the issuing of antigen-matched blood (at least for E antigen).

The Areal Project: How Virtual Reality Application Could Enhance Patient's Quality Time during Transfusion Therapy in Adult Patients with Thalassemia and Sickle Cell Disease

Background Chronic red blood cell transfusion therapy (CTT) is an integral component of the management of Transfusion Dependent Thalassemia (TDT) and Sickle Cell Disease (SCD). CTT requires time and significantly impacts the quality of life of patients with TDT and SCD. In some cases, the environment in which transfusions are performed is uncomfortable and doesn't offer adequate spaces and facilities. And as a result, the patient experiences a condition of discomfort and tries with his own means to get distracted or "estranged". Hence, attention should be paid to psychological, emotional and social needs of patients on CTT in order to reduce the burden of the procedure with activities that are capable of engaging more the person. Aims From this need and the opportunities offered by the digital technologies available today, the AREAL project was designed by the Italian startup Softcare Studios in partnership with the pharma company Novartis and in collaboration with hemoglobinopathy specialized medical staff. Objectives of this pilot project were: i) collect feedback from patients with TDT and SCD and from healthcare professional workers regarding utility and feasibility of AREAL; ii) detect and evaluate changing in states of patient's anxiety and depression. Methods AREAL consists of three gaming activities enjoyed in virtual reality thanks to the use of suitable Virtual Reality (VR) viewers (Figure 1A) developed to immerse the patient in a sensorial stimulating scenario and designed to stimulate cognitive skills: activity 1 for short-term memory, activity 2 for task switching, activity 3 for problem solving. AREAL also integrates elements of patient education in therapy and recommended lifestyle habits to promote their well-being. Anxiety and depression were assessed by a self-assessment questionnaire, the Hospital Anxiety and Depression Scale (HADS), administered after each virtual session. Results The pilot group was composed by 70 subjects on CTT followed in 3 hospital centers in Italy (Genova, Napoli, Padova). The 57% were males, median age was 31 years (IQR: 21-40), 53 patients were affected by TDT and 6 by SCD. The total number of sessions collected is 129; 59 patients experienced two sessions and were included in the analysis for HADS. The average duration of game sessions lasted 17 minutes.Activity 1 was the most played and most rarely interrupted, followed by 2 and finally by 3, where 50% of sessions are been interrupted due to its difficulty. In Activity 1 patients recognized the goal of the game, which is to stimulate memory, and they liked its immediacy. Excessive facility, especially considering the repetition over time during the therapy, was emphasized by patients who suggested making the game more complicated. Compared to Activity 1, Activity 2 is more complicated and engaging, emerging as the overall favorite of the study patients. Undoubtedly, Activity 3 emerged as the most difficult one, both to play and to understand, also given its focus on problem solving. Based on the feedback from healthcare professionals learning to use the virtual application wasn't particularly difficult. The experience of the staff confirmed some of the critical issues also communicated by patients (such as the high difficulty of the third game activity and request for greater variability over time).Anxiety and depression were detected by HADS respectively in 13 and in 9 pts after first session, in 10 and in 4 pts after second session, suggesting a possible benefit of VR; the number of patients with borderline profile reduced from 8 to 3 both for anxiety and depression (Figure 1B). There were no significant differences of scores and/or percentages between sessions. Conclusions There is a significant need to iterate AREAL on the basis of different age groups, each with specific needs, preferences and level of confidence with technologies. From the collected feedback, AREAL was perceived as an innovative project and an opportunity to pay attention to the critical issues of the patients' therapeutic experience on CTT. However, it is needed to optimize the experience in order to free the operator from extra commitments as much as possible that could impact the quality of hospital work routine. AREAL seems to be an opportunity to reduce discomfort and anxiety during CCT in the subset of pts with a profile borderline for anxiety and depression but needs to tailor the intervention to specific subsets of patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

EVALUATION OF THE COST AND EFFECT OF PROPHYLACTIC GENOTYPIC MATCHING ON ALLOIMMUNIZATION AND AUTOIMMUNIZATION IN PATIENTS WITH SICKLE CELL DISEASE (SCD)

Blood transfusion is one of the mainstays of treatment for patients with SCD but despite of the beneficial effects, transfusion therapy can lead to red blood cell (RBC) alloimmunization with serious complications for the patient including life-threatening delayed hemolytic transfusion reactions and the hyperhemolysis syndrome. In addition, the presence of alloantibodies, which is often associated with the concomitant presence of autoantibodies, can lead to difficulty in finding compatible units, which can cause transfusion delays. To reduce alloimmunization some strategies have been implemented to provide antigen matched RBC transfusions to patients with SCD who need chronic transfusion support. In this context, phenotypic and genotypic matching protocols have been used. Based on this, the aim of this study was to evaluate the cost and the effect of prophylactic RBC transfusion genotypic matching on alloimmunization and autoimmunization in patients with SCD. Our study included 79 (33 male and 46 female) patients with SCD, homozygous for HbS, on chronic RBC transfusion therapy receiving prophylactic genotypic matching RBC transfusions in the last two years. In this period, patients received RBC units genotypic matched for Rh, K, Fya/Fy/b, Jka/Jkb, S/s, Doa/Dob and Dia antigens. Molecular matching was performed according to previous molecular typing results performed by the HEA BeadChip (Immucor) in patients and donors. Adsorption onto autologous RBC was also performed to aid the differentiation of autoantibodies from alloantibodies. The cost and availability of compatible units by performing genotypic matching were compared to serologic matching. The patients received a range of 5-215 units. And the median age in this group was 39 years old. Of the 79 patients, 17 (21.5%) were alloimmunized before they started receiving genotypic matched RBC transfusions. During this study-period only 2 patients (2.5%) with Rh variants developed alloantibodies (1 anti-C, 1 anti-e) and no patient produced autoantibody. Although the availability of compatible units has decreased when compared to serological matching, it was possible to find compatible units for most patients. A cost reduction of 30% was observed in the genotypic matching compared to the serological matching for the selected matched antigens. RBC transfusions with extended genotypic matching had significant effects on autoimmunization and alloimmunization rates in chronically transfused patients with SCD over two years. Alloimmunization rates have shown to decrease from a range of 21.5 to 2.5% in these patients. SCD patients may benefit from receiving prophylactic genotypic matching RBC transfusions as demonstrated by the reduction on the rates of alloimmunization, autoimmunization and cost.

Normalization of cerebral hemodynamics after hematopoietic stem cell transplant in children with sickle cell disease

AbstractChildren with sickle cell disease (SCD) demonstrate cerebral hemodynamic stress and are at high risk of strokes. We hypothesized that curative hematopoietic stem cell transplant (HSCT) normalizes cerebral hemodynamics in children with SCD compared with pre-transplant baseline. Whole-brain cerebral blood flow (CBF) and oxygen extraction fraction (OEF) were measured by magnetic resonance imaging 1 to 3 months before and 12 to 24 months after HSCT in 10 children with SCD. Three children had prior overt strokes, 5 children had prior silent strokes, and 1 child had abnormal transcranial Doppler ultrasound velocities. CBF and OEF of HSCT recipients were compared with non-SCD control participants and with SCD participants receiving chronic red blood cell transfusion therapy (CRTT) before and after a scheduled transfusion. Seven participants received matched sibling donor HSCT, and 3 participants received 8 out of 8 matched unrelated donor HSCT. All received reduced-intensity preparation and maintained engraftment, free of hemolytic anemia and SCD symptoms. Pre-transplant, CBF (93.5 mL/100 g/min) and OEF (36.8%) were elevated compared with non-SCD control participants, declining significantly 1 to 2 years after HSCT (CBF, 72.7 mL/100 g per minute; P = .004; OEF, 27.0%; P = .002), with post-HSCT CBF and OEF similar to non-SCD control participants. Furthermore, HSCT recipients demonstrated greater reduction in CBF (−19.4 mL/100 g/min) and OEF (−8.1%) after HSCT than children with SCD receiving CRTT after a scheduled transfusion (CBF, −0.9 mL/100 g/min; P = .024; OEF, −3.3%; P = .001). Curative HSCT normalizes whole-brain hemodynamics in children with SCD. This restoration of cerebral oxygen reserve may explain stroke protection after HSCT in this high-risk patient population.

Clinical characteristics and risk factors associated with ICU-acquired infections in sepsis: A retrospective cohort study.

Intensive care unit (ICU)-acquired infection is a common cause of poor prognosis of sepsis in the ICU. However, sepsis-associated ICU-acquired infections have not been fully characterized. The study aims to assess the risk factors and develop a model that predicts the risk of ICU-acquired infections in patients with sepsis.MethodsWe retrieved data from the Medical Information Mart for Intensive Care (MIMIC) IV database. Patients were randomly divided into training and validation cohorts at a 7:3 ratio. A multivariable logistic regression model was used to identify independent risk factors that could predict ICU-acquired infection. We also assessed its discrimination and calibration abilities and compared them with classical score systems.ResultsOf 16,808 included septic patients, 2,871 (17.1%) developed ICU-acquired infection. These patients with ICU-acquired infection had a 17.7% ICU mortality and 31.8% in-hospital mortality and showed a continued rise in mortality from 28 to 100 days after ICU admission. The classical Systemic Inflammatory Response Syndrome Score (SIRS), Sequential Organ Failure Assessment (SOFA), Oxford Acute Severity of Illness Score (OASIS), Simplified Acute Physiology Score II (SAPS II), Logistic Organ Dysfunction Score (LODS), Charlson Comorbidity Index (CCI), and Acute Physiology Score III (APS III) scores were associated with ICU-acquired infection, and cerebrovascular insufficiency, Gram-negative bacteria, surgical ICU, tracheostomy, central venous catheter, urinary catheter, mechanical ventilation, red blood cell (RBC) transfusion, LODS score and anticoagulant therapy were independent predictors of developing ICU-acquired infection in septic patients. The nomogram on the basis of these independent predictors showed good calibration and discrimination in both the derivation (AUROC = 0.737; 95% CI, 0.725–0.749) and validation (AUROC = 0.751; 95% CI, 0.734–0.769) populations and was superior to that of SIRS, SOFA, OASIS, SAPS II, LODS, CCI, and APS III models.ConclusionsICU-acquired infections increase the likelihood of septic mortality. The individualized prognostic model on the basis of the nomogram could accurately predict ICU-acquired infection and optimize management or tailored therapy.

Iron Effects on Clostridioides difficile Toxin Production and Antimicrobial Susceptibilities.

Despite the benefits of red blood cell (RBC) transfusion therapy, it can render patients vulnerable to iron overload. The excess iron deposits in various body tissues cause severe complications and organ damage such as cardiotoxicity and mold infections. Clostridioides difficile infection (CDI) is the most common cause of nosocomial diarrhea among cancer patients and is associated with significant morbidity and mortality. Our study aims to determine the role of iron overload and the effects of iron chelators on CDI. Our results demonstrated that iron (Fe3+) stimulated the growth of C. difficile with increased colony formation units (CFU) in a dose-dependent manner. Exposure to excess iron also increased the gene expression levels of tcdA and tcdB. The production of C. difficile toxin A, necessary for the pathogenesis of C. difficile, was also elevated after iron treatment. In the presence of excess iron, C. difficile becomes less susceptible to metronidazole with significantly elevated minimum inhibitory concentration (MIC) but remains susceptible to vancomycin. Iron-stimulated colony formation and production of C. difficile toxins were effectively diminished by iron chelator deferoxamine co-treatment. Incorporating iron overload status as a potential factor in developing a risk prediction model of CDI and antibiotic treatment response may aid clinical practitioners in optimizing CDI management in oncology patients.

The use of non-cryopreserved hematopoietic stem cells for autologous transplantation in multiple myeloma patients

Background . An autologous stem cell transplant (ASCT) is the standard of treatment young and fit patients with multiple myeloma (MM). The using this method of treatment is limited due to the high consumption of economic and intellectual resources, the low availability of Cryobank departments in regions of Russia. Objective : to evaluate the efficacy and safety of using non-cryopreserved peripheral blood stem cells (non-CRYO PBSCs) in patients with multiple myeloma who underwent autologous transplantation. Materials and methods . We conducted a prospective study of the efficacy and safety of using non-CRYO PBSCs in patients with MM who underwent ASCT. The number of PBSCs apheresis procedures in 82.9 % (n = 29 pts) was 1 day, and in 17.1 % (n = 6 pts) was 2 days. After apheresis, PBSCs were stored at a temperature of +4…+6 °C in a blood bank refrigerator for up to 72 hours. During 4 years, ASCT using non-CRYO PBSCs was performed in 35 patients with MM. The average number CD34+ cell dose was 2.63 × 106 /kg. The median time to neutrophil engraftment was 11 days (range from 9 to 14). The median time to platelet engraftment was 12 days (range from 8 to 19). The control group included 43 patients with MM, who underwent PBSCs ASCT according to the traditional method, including preparation and cryopreservation of the apheresis product of PBSCs with cryoprotectant dimethyl sulfoxide, as well as subsequent defrosting on the day of transplantation (day 0). Results . There were no significant differences comparing the safety of ASCT in non-CRYO and CRYO PBSCs groups among such parameters as the viability of PBSCs, the frequency of complications, the time of hematopoietic engraftment, the need for platelet and red blood cells transfusion therapy, and time of hospitalization. Conclusion . Hence, the method of short-term storaging non-CRYO PBSCs is not inferior to the traditional method of controlled freezing, is more economical and can be used in medical organizations that do not have a Cryobank in their structure.

Comparison of outcomes between variceal and non-variceal gastrointestinal bleeding in patients with cirrhosis: Insights from a Nationwide Inpatient Sample.

Variceal upper gastrointestinal bleeding (VUGIB) occurs in patients with decompensated cirrhosis, but non-VUGIB (NVUGIB) is not uncommon. We compared the outcomes of VUGIB and NVUGIB in cirrhotic patients. This retrospective study used Nationwide Inpatient Sample employing International Classification of Diseases codes for adult NVUGIB and VUGIB patients. Mortality, morbidity, and resource utilization were compared. Analyses were performed using STATA; proportions and continuous variables were compared using Fisher's exact and Student's t-test, respectively. Confounding variables were adjusted using propensity matching, multivariate logistic and linear regression analyses. Of 2,166,194 cirrhotics, 92,439 had a diagnosis of NVUGIB and 17,620 VUGIB. VUGIB patients had higher rates of mortality [adjusted odds ratio (aOR) 1.42, 95% confidence interval (CI) 1.19-1.69], hemorrhagic shock (aOR 1.84, 95%CI 1.54-2.17) and intensive care unit admission (aOR 2.47, 95%CI 2.18-2.81), greater hospitalization costs ($16,251 vs. $12,295, P<0.001), more need for packed red blood cell transfusion (aOR 1.12, 95%CI 1.03-1.22) or endoscopic therapy (aOR 2.71, 95%CI 2.47-2.93), and a longer hospital stay compared to NVUGIB. However, NVUGIB had higher aOR of undergoing diagnostic endoscopy and radiography-guided vessel embolization. There were no differences in the rates of acute kidney injury between the 2 groups. Ascites and spontaneous bacterial peritonitis were independently associated with increased VUGIB mortality. VUGIB in patients with cirrhosis is associated with greater hospital costs, mortality, and morbidity burden than NVUGIB. This study provides updated and current knowledge of patient characteristics and differences in outcomes between VUGIB and NVUGIB, required to successfully address the healthcare delivery gaps.

Quality of Care in United States Children with Sickle Cell Anemia

Quality of Care in United States Children with Sickle Cell Anemia

Analysis of Baseline Clinical Characteristics and Disease Burden in Patients Enrolled in the International Paroxysmal Nocturnal Hemoglobinuria Registry

Background/Objective: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, potentially life-threatening hematologic disorder characterized by chronic uncontrolled intravascular hemolysis, thrombosis, end organ damage, and impaired quality of life (QoL) and survival. The International PNH Registry (NCT01374360) is an ongoing, global observational study to evaluate the safety profile of eculizumab and to characterize the burden and progression of PNH including clinical outcomes, morbidity, and mortality irrespective of treatment. The objective of this analysis was to characterize the demographic and clinical characteristics, disease-associated morbidities, PNH symptoms, and health-related QoL of the largest cohort of PNH patients enrolled in the Registry.Methods: Registry patients who had data available as of May 1, 2017, were eligible for the current analysis. All patients were untreated at baseline, defined as the date of eculizumab initiation for patients ever treated with eculizumab and the date of Registry enrollment for patients never treated with eculizumab. Proportions of patients with high disease activity (HDA), history of major adverse vascular events (MAVE; including thrombotic events [TE]) and bone marrow disorders (BMD) including aplastic anemia, red blood cell (RBC) transfusions, concomitant medication use, and physician-reported symptoms were based on the number of patients with non-missing responses at baseline. Laboratory values and QoL scores assessed with the European Organisation for Research and Treatment of Cancer [EORTC] Global Health and Functional Assessment of Chronic Illness Therapy [FACIT]-Fatigue questionnaires within 6 months prior to baseline were summarized using medians and quartiles or proportions for the patients with non-missing responses. Patients with percent glycosylphosphatidylinositol (GPI)-deficient granulocyte values available prior to baseline were stratified based on the most recent value prior to baseline and statistical analysis (i.e., P values) was used to assess potential trends related to clone size.Results: A total of 4903 patients were enrolled. Of these, 4398 had non-missing data on demographics, enrollment date, and eculizumab status, and were eligible for the analysis. Median (Q1, Q3) age at disease onset was 35.3 (23.9, 53.1) years; 53% of the patients were female. Median (Q1, Q3) percent GPI-deficient granulocyte clone size was 33% (3%, 85%) in the 2654 patients with clone size reported prior to baseline. Clinical characteristics at baseline for the overall population and stratified by percent GPI-deficient clone size are summarized in the Table. Overall, patients had a high burden of disease at baseline, as reflected by the proportion with HDA (52%), history of MAVE (19%), BMD (63%), RBC transfusions (61%), and impaired renal function defined as estimated glomerular filtration rate <90 mL/min (42%). Patients frequently experienced symptoms such as fatigue (81%), dyspnea (45%), hemoglobinuria (45%), abdominal pain (35%), and impaired QoL with median (Q1, Q3) FACIT-Fatigue and EORTC Global Health scores of 34.0 (27.0, 40.0) and 58.3 (41.7, 75.0), respectively. All measures of disease burden except for history of RBC transfusions were significantly correlated with clone size (P <0.05); specifically, higher disease burden correlated with larger clone size. However, a substantial number of patients with clone size <10% had hemolysis (LDH ≥1.5 x ULN; 10%), MAVE (10%), HDA (9%), and/or experienced symptoms such as fatigue (82%), dyspnea (46%), abdominal pain (19%), or hemoglobinuria (13%). History of RBC transfusion and immunosuppressive therapy were reported in 60% and 59% of patients with clone size <10%, potentially due to patients with history of BMD. Interestingly, median LDH ratio and the proportion of patients with history of MAVE and TE were modestly higher in the cohort with clone size 10-<50% vs <10%, while the proportion of those patients was substantially higher in the cohort with clone size ≥50% vs 10-<50%.Conclusions: PNH is associated with high burden of disease, particularly in patients with larger GPI-deficient clone sizes; however, even patients with smaller clone sizes had significant disease burden and symptoms. Improved characterization of clinical measures and of relationships between these measures may help inform patient management. [Display omitted] DisclosuresSchrezenmeier:Alexion Pharmaceuticals, Inc.: Honoraria, Other: Research Funding to University of Ulm . Maciejewski:Ra Pharma: Consultancy; Alexion Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Speaker Fees; Apellis Pharmaceuticals: Consultancy. Roeth:Roche: Consultancy, Honoraria; Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria. Araten:Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria. Kanakura:Alexion Pharmaceuticals, Inc.: Honoraria, Research Funding; Astellas: Research Funding; Bristol Myers: Research Funding; Toyama Chemical: Research Funding; Kyowa Hakko Kirin: Research Funding; Eisai: Research Funding; Shionogi: Research Funding; Fujimotoseiyaku: Research Funding; Pfizer: Research Funding; Nippon Shinyaku: Research Funding; Chugai Pharmaceutical: Research Funding. Larratt:Alexion Pharmaceuticals, Inc.: Honoraria, Other: Research Funding to the laboratory at University of Alberta, for ADAMTS13 testing. Shammo:Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria, Research Funding. Wilson:Alexion Pharmaceuticals, Inc.: Employment, Equity Ownership. Shayan:Alexion Pharmaceuticals, Inc.: Employment, Equity Ownership. Hillmen:Gilead: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; GSK: Consultancy, Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Pharmacyclics LLC, an AbbVie Company: Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria; Celgene: Research Funding; Roche: Consultancy, Honoraria, Research Funding.

Luspatercept as a therapy for myelodysplastic syndromes with ring sideroblasts

ABSTRACT Introduction Myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic stem cell diseases characterized by cell dysplasia, ineffective hematopoiesis and risk of transformation to acute myeloid leukemia (AML). The median age of 75 years at diagnosis is associated with the presence of comorbidities, which preclude intensive therapies like allogeneic hematopoietic stem cell transplantation in most MDS patients. Risk stratification using the (Revised) International Prognostic Scoring System (IPSS/IPSS-R) is necessary to plan individualized treatment. Areas covered Luspatercept (ACE-536), a specific activin receptor fusion protein, promotes late-stage erythropoiesis. Two clinical trials, PACE-MDS (phase 2) and MEDALIST (phase 3), yielded positive results in terms of improved hemoglobin levels and loss of transfusion dependence, with hardly any side effects. A phase 3 trial to compare luspatercept to ESAs (COMMANDS study) is ongoing. Expert opinion Luspatercept is a promising alternative to ESAs for a subset of transfusion-dependent patients with lower risk MDS, namely those with a sideroblastic phenotype who are either not suitable for or have already failed erythropoietin-based treatment. The favorable safety profile and convenient subcutaneous administration every 3 weeks are more conducive to patients’ quality of life than chronic red blood cell transfusion therapy.

Machine learning models to predict red blood cell transfusion in patients undergoing mitral valve surgery.

Red blood cell (RBC) transfusion therapy has been widely used in surgery, and has yielded excellent treatment outcomes. However, in some instances, the demand for RBC transfusion is assessed by doctors based on their experience. In this study, we use machine learning models to predict the need for RBC transfusion during mitral valve surgery to guide the surgeon's assessment of the patient's need for intraoperative blood transfusion. We retrospectively reviewed 698 cases of isolated mitral valve surgery with and without combined tricuspid valve operation. Seventy percent of the database was used as the training set and the remainder as the testing set for 13 machine learning algorithms to build a model to predict the need for intraoperative RBC transfusion. According to the characteristic value of model mining, we analyzed the risk-related factors to determine the main effects of variables influencing the outcome. A total of 166 patients of the cases considered had undergone intraoperative RBC transfusion (24.52%). Of the 13 machine learning algorithms, CatBoost delivered the best performance, with an AUC of 0.888 (95% CI: 0.845-0.909) in testing set. Further analysis using the CatBoost model revealed that hematocrit (<37.81%), age (>64 y), body weight (<59.92 kg), body mass index (BMI) (<22.56 kg/m2), hemoglobin (<122.6 g/L), type of surgery (median thoracotomy surgery), height (<160.61 cm), platelet (>194.12×109/L), RBC (<4.08×1012/L), and gender (female) were the main risk-related factors for RBC transfusion. A total of 204 patients were tested, 177 of whom were predicted accurately (86.8%). Machine learning models can be used to accurately predict the outcomes of RBC transfusion, and should be used to guide surgeons in clinical practice.

Enhanced recovery after low- and medium-risk liver transplantation. A single-center prospective observational cohort study

Background & aimsFew studies have fully applied an enhanced recovery after surgery (ERAS) protocol to liver transplantation (LT). Our aim was to assess the effects of a comprehensive ERAS protocol in our cohort of low- and medium-risk LT patients. MethodsThe ERAS protocol included pre-, intra-, and post-operative steps. During the five-year study period, 181 LT were performed in our institution. Two cohorts were identified: low risk patients (n = 101) had a laboratory model for end-stage liver disease (MELD) score of 20 points or less at the time of LT, received a liver from a donor after brain death, and had a balance of risk score of 9 points or less; medium-risk patients (n = 15) had identical characteristics except for a higher MELD score (21–30 points). In addition, we analyzed the remaining patients (n = 65) who were transplanted over the same study period separately using the ERAS protocol. ResultsThe low-risk cohort showed a low need for packed red blood cells transfusion (median: 0 units) and renal replacement therapy (1%), as well as a short length of stay both in the intensive care unit (13 h) and in the hospital (4 days); morbidity during one-year follow-up, and probability of surviving to one year (89.30%) and five years (76.99%) were in line with well-established reference data. Similar findings were observed in the medium-risk cohort. ConclusionsThis single-center prospective observational cohort study provides evidence that ERAS is feasible and safe for low- and medium-risk LT.