Red Blood Cell Transfusion Requirements Research Articles

Allogeneic Umbilical Cord Blood Red Cell Concentrates: An Innovative Blood Product for Transfusion Therapy of Preterm Infants

Background: Preterm infants often receive blood transfusions early in life. In this setting, umbilical cord blood (UCB) might be safer than adult blood (A) with respect to infectious and immunologic threats. Objectives: To evaluate, as a first objective, the feasibility of fulfilling transfusion needs of preterm infants with allogeneic UCB red blood cell (RBC) concentrates and, as a secondary objective, to assess the safety of allogeneic cord blood transfusions. Methods: At the Neonatal Intensive Care Unit and the UNICATT Cord Blood Bank of ‘A. Gemelli' Hospital in Rome, a prospective study was carried out over a 1-year period, enrolling newborns with gestational age ≤30 weeks and/or birth weight ≤1,500 g requiring RBC transfusions within the first 28 days of life. At first transfusion, patients were assigned to receive UCB-RBCs or A-RBCs depending on the availability of ABO-Rh(D)-matched UCB-RBC units. The same regimen (UCB-RBC or A-RBC units) was thereafter maintained, unless ABO-Rh(D)-matched UCB-RBC units were not available. Results: Overall, 23 UCB-RBC units were transfused to 9 patients; the requests for UCB-RBC units were met in 45% of patients at the first transfusion and in 78% at the subsequent transfusions. At a median follow-up of 57 days (range 6-219), no acute or delayed transfusion-related adverse events occurred. Hematocrit gain after transfusion and time intervals between transfusions were similar in the UCB-RBC and A-RBC group, as well. Conclusions: Transfusing allogeneic UCB-RBC units in preterm infants appears a feasible and safe approach, although the transfusion needs of our study population were not completely covered. More data are necessary to validate this novel transfusion practice. © 2014 S. Karger AG, Basel

Erythropoietin use in the newborn

The first descriptions of blood transfusion in neonates date back to the nineteenth century. Time is past but uncertainties still remain considerable on optimal red blood cell (RBC) transfusion use in an era of evidence-based medicine. The need for RBC transfusion in critically ill neonates is differently judged among clinicians due to a lack of an agreement on measures of the need for transfusion. However some studies have shown an association between preterm infant morbidities, such as necrotizing enterocolitis and significant intracranial hemorrhage, with transfusions. The erythropoietin (EPO) use might prove clinically important. Physiologically in all newborns there is a progressive fall in hemoglobin concentrations to the nadir at about 8–12 weeks of life. The nadir is even lower and sooner in preterm neonates. This anemia of prematurity is the consequence of multiple factors, some are physiological processes as vulnerability of red cells to oxidative damage, reduced red cell lifespan when compared to the adult, lower erythropoietin (EPO) response to anemia than in older ages, increased requirements due to the postnatal growth; some are non-physiological processes as iatrogenic blood sampling, inter-current illnesses and sepsis. All these factors are responsible for low plasma EPO concentration in preterm newborns. This provides a rationale for the use of EPO in prophylaxis or treatment of the anemia. EPO has been used clinically for more than 20 years and many randomized clinical trials demonstrated that EPO successfully stimulate erythropoiesis and decrease the need of transfusion in anemic adults and children with end-stage renal disease or cancer. Differently in preterm newborns, the EPO treatment has demonstrated varied success in decreasing the total number and volume of transfusions. There are not clear evidences from high quality trials to define the absolute requirement and benefit for neonatal RBC transfusion. A recent Cochrane metanalysis performed by Ohlsson A. and Aher S.M. (1) to assess the effectiveness and safety of early initiation of EPO or darbepoetin in reducing RBC transfusions in preterm and/or low birth weight infants, concludes that the small reductions in RBC transfusion observed after EPO treatment are of limited clinical importance. In contrast the possibly increased risk of ROP, does not recommend the administration of EPO. Darbepoetin requires further study for definitive conclusions.

What is the Clinical Effectiveness of Erythropoiesis Stimulating Agents for the Treatment of Cancer Treatment-Induced Anaemia?

Aim: Anaemia is a common side-effect of cancer treatments and can lead to a reduction in quality of life. Erythropoiesis-stimulating agents (ESAs) are licensed for use in conjunction with red blood cell transfusions (RBCTs) to improve cancer treatment-induced anaemia (CIA). We aim to review the clinical-effectiveness evidence for ESAs for treating CIA. Methods: The clinical effectiveness review followed principles published by the NHS CRD. Electronic databases and grey literature sources were searched up to December 2013. Randomised controlled trials (RCTs) comparing ESAs in accordance with their EU licenses (based on start dose administered) with best supportive care, placebo, or other ESA in adults with CIAwere included. Anaemia- and malignancy-related outcomes, health-related quality of life (HRQoL), and adverse events (AEs) were extracted from primary studies. Where appropriate, data were pooled using random-effects meta-analyses. Results: Twenty-three RCTs were included in the review. None of the RCTs were completely aligned with current EU licenses. Results suggest that there is clinical benefit from ESAs for anaemia-related outcomes. Sixty-three percent of participants who received ESAs achieved a haematological response compared with 18% of participants who did not receive ESAs, and there was a reduction in requirement for RBCT by an estimated 37% with ESAs. Data also suggest some improvement in HRQoL scores (FACT-F, FACT-G and FACT-An). The impact of ESAs on malignancy-related outcomes and AEs is uncertain. The overall survival (OS) results (HR 0.97, 95% CI 0.83, 1.13, I 2 of 42.4%) suggest no effect of ESAs on OS. Although all AEs were relatively rare (max. 6%), an increased risk for thromboembolic events, pruritus and hypertension was found. Post-hoc sensitivity analyses suggested that the effectiveness for some outcomes was improved when ESAs were evaluated ‘closer to licence’. Conclusions: Although results from the review suggest that ESAs may be beneficial when used closer to their licensed indications, this trend should be interpreted with caution due to high statistical heterogeneity, wide confidence intervals, multiple testing, and the licence interpretation. Disclosure: All authors have declared no conflicts of interest.

Risk factors for delayed infections after spinal fusion and instrumentation in patients with scoliosis. Clinical article.

There are limited published data about the risk factors for the development of delayed infections after spinal fusion and instrumentation in the population with scoliosis. The objective of this study was to evaluate the predictive factors of development of delayed infections in patients with scoliosis who underwent surgical treatment. A total of 17 patients with scoliosis and delayed infections were identified from 3463 patients with scoliosis who received surgical treatment. The control group was composed of 85 patients with scoliosis without infections, matched for sex, age, approximate date of surgery, and diagnosis. These 2 groups were compared for demographic distribution and clinical data to investigate the predictive factors of delayed infections. The overall incidence rate of delayed infections was 0.49%. The variables of age, body mass index, and number of levels fused were similar between the 2 groups. The average primary curve magnitude for the delayed infection and control (uninfected) groups was 80.4° ± 27.0° (range 47°-135°) and 66.3° ± 11.6° (range 42°-95°), respectively (p = 0.001). Operation time in the group with delayed infections was 384.7 ± 115.9 minutes versus 254.4 ± 79.2 minutes in the control group (p = 0.000), and estimated blood loss was 1342.2 ± 707.2 ml versus 833.9 ± 235.6 ml (p = 0.000) in these 2 groups, respectively. The perioperative mean red blood cell transfusion requirement in the delayed infection group was significantly higher than that found in patients without infections (2.8 ± 2.3 units/patient versus 1.1 ± 1.6 units/patient, respectively; p = 0.000). Logistic regression analysis showed that operation time and allogenic blood transfusion were the 2 independent predictors of delayed infections (odds ratio [OR] 1.021, 95% confidence interval [CI] 1.010-1.033, and OR 1.546, 95% CI 1.048-2.278, respectively). The occurrence of a delayed infection in patients with scoliosis who undergo surgical treatment is most likely multifactorial and is related to surgical time and the use of allogenic blood transfusion.

Efficacy of autologous blood withdrawal-reinfusion for scoliosis surgery: a retrospective analysis based on propensity score matching

Objective To evaluate the efficacy of autologous blood withdrawal-reinfusion for scoliosis surgery.Methods Six hundred and seventy-seven patients of both sexes,aged 7-64 yr,weighing 20-83 kg,who underwent scoliosis surgery from August 2007 to November 2013,were randomly divided into 2 groups according to whether or not autologous blood withdrawal-reinfusion was applied:control group (group C,n =474) and autologous blood withdrawal-reinfusion group (group WR,n =203).Propensity score matching analysis with preset caliper width was used.A total of 181 matched pairs were selected from the patients.The intra-operative and post-operative requirements for allogeneic red blood cell (RBC) and plasma transfusion and peri-operative blood transfusion-related cost were recorded.Results Compared with group C,the intraoperative requirement for allogeneic RBC transfusion was siguificantly decreased,the cost was increased,and no significant change was found in perioperative requirements for allogeneic RBC and plasma transfusion in group WR.Conclusion Although autologous blood withdrawal-reinfusion can reduce the intraoperative requirement for allogeneic RBC transfusion,it can not reduce the perioperative requirement for allogeneic blood transfusion,and increases the cost of perioperative blood transfusion when used for scoliosis surgery,thus providing no significant value clinically. Key words: Blood transfusion, autologous; Scoliosis; Propensity score

Heterogeneous Phenotypes of Acute Respiratory Distress Syndrome after Major Trauma

Acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome that can develop at various times after major trauma. To identify and characterize distinct phenotypes of ARDS after trauma, based on timing of syndrome onset. Latent class analyses were used to identify patterns of ARDS onset in a cohort of critically ill trauma patients. Identified patterns were tested for associations with known ARDS risk factors and associations were externally validated at a separate institution. Eleven plasma biomarkers representing pathophysiologic domains were compared between identified patterns in the validation cohort. Three patterns of ARDS were identified; class I (52%) early onset on Day 1 or 2, class II (40%) onset on Days 3 and 4, and class III (8%) later onset on Days 4 and 5. Early-onset ARDS was associated with higher Abbreviated Injury Scale scores for the thorax (P < 0.001), lower lowest systolic blood pressure before intensive care unit admission (P = 0.003), and a greater red blood cell transfusion requirement during resuscitation (P = 0.030). In the external validation cohort, early-onset ARDS was also associated with a higher Abbreviated Injury Scale score for the thorax (P = 0.001) and a lower lowest systolic blood pressure before intensive care unit enrollment (P = 0.006). In addition, the early-onset phenotype demonstrated higher plasma levels of soluble receptor for advanced glycation end-products and angiopoietin-2. Degree of hemorrhagic shock and severity of thoracic trauma are associated with an early-onset phenotype of ARDS after major trauma. Lung injury biomarkers suggest a dominant alveolar-capillary barrier injury pattern in this phenotype.

Subcutaneous bortezomib is highly effective for pure red cell aplasia after ABO‐incompatible haematopoietic stem cell transplantation

Subcutaneous bortezomib is highly effective for pure red cell aplasia after <scp>ABO</scp>‐incompatible haematopoietic stem cell transplantation

Biofilms and persistent wound infections in United States military trauma patients: a case–control analysis

BackgroundComplex traumatic injuries sustained by military personnel, particularly when involving extremities, often result in infectious complications and substantial morbidity. One factor that may further impair patient recovery is the persistence of infections. Surface-attached microbial communities, known as biofilms, may play a role in hindering the management of infections; however, clinical data associating biofilm formation with persistent or chronic infections are lacking. Therefore, we evaluated the production of bacterial biofilms as a potential risk factor for persistent infections among wounded military personnel.MethodsBacterial isolates and clinical data from military personnel with deployment-related injuries were collected through the Trauma Infectious Disease Outcomes Study. The study population consisted of patients with diagnosed skin and soft-tissue infections. Cases (wounds with bacterial isolates of the same organism collected 14 days apart) were compared to controls (wounds with non-recurrent bacterial isolates), which were matched by organism and infectious disease syndrome. Potential risk factors for persistent infections, including biofilm formation, were examined in a univariate analysis. Data are expressed as odds ratios (OR; 95% confidence interval [CI]).ResultsOn a per infected wound basis, 35 cases (representing 25 patients) and 69 controls (representing 60 patients) were identified. Eight patients with multiple wounds were utilized as both cases and controls. Overall, 235 bacterial isolates were tested for biofilm formation in the case–control analysis. Biofilm formation was significantly associated with infection persistence (OR: 29.49; CI: 6.24-infinity) in a univariate analysis. Multidrug resistance (OR: 5.62; CI: 1.02-56.92), packed red blood cell transfusion requirements within the first 24 hours (OR: 1.02; CI: 1.01-1.04), operating room visits prior to and on the date of infection diagnosis (OR: 2.05; CI: 1.09-4.28), anatomical location of infected wound (OR: 5.47; CI: 1.65-23.39), and occurrence of polymicrobial infections (OR: 69.71; CI: 15.39-infinity) were also significant risk factors for persistent infections.ConclusionsWe found that biofilm production by clinical strains is significantly associated with the persistence of wound infections. However, the statistical power of the analysis was limited due to the small sample size, precluding a multivariate analysis. Further data are needed to confirm biofilm formation as a risk factor for persistent wound infections.

Does intraoperative cell salvage system effectively decrease the need for allogeneic transfusions in scoliotic patients undergoing posterior spinal fusion? A prospective randomized study

To determine the safety and efficacy of intraoperative cell salvage system in decreasing the need for allogeneic transfusions in a cohort of scoliosis patients undergoing primary posterior spinal fusion with segmental spinal instrumentation. A total of 110 consecutive scoliosis patients undergoing posterior instrumented spinal fusion were randomized into two groups according to whether a cell saver machine for intraoperative blood salvage was used or not. Data included age, body mass index, perioperative hemoglobin levels, surgical time, levels fused, perioperative estimated blood loss, perioperative transfusions and incidence of transfusion-related complications. A Chi-square test and t tests were performed for intraoperative and perioperative allogeneic transfusion between groups. A regression analysis was performed between selected covariates to investigate the predictive factors of perioperative transfusion. Perioperative allogenic blood transfusion rate was lower in the cell saver group (14.5 versus 32.7%, p = 0.025). Mean intraoperative red blood cell transfusion requirement was also lower (0.21 U/pt versus 0.58 U/pt, p = 0.032). A multivariate analysis demonstrated that no. of fused segments (OR: 1.472; p = 0.005), preoperative hemoglobin level (OR: 0.901; p = 0.001), and the use of cell saver system (OR: 0.133; p = 0.003) had a trend toward significance in predicting likelihood of transfusion. Cell saver use significantly reduces the need for allogeneic blood in spine deformity surgery, particularly in patients with low preoperative hemoglobin or longer operation time. This study confirms the utility of routine cell saver use during PSF with segmental spinal instrumentation for scoliosis patients.

Operative outcomes of adult living donor liver transplantation and deceased donor liver transplantation: A systematic review and meta-analysis

Living donor liver transplantation (LDLT) has emerged as an alternative to deceased donor liver transplantation (DDLT) because of the increasing number of patients waiting for liver transplantation (LT). However, whether it can achieve operative outcomes similar to those achieved with DDLT for adult patients remains controversial. We conducted this meta-analysis to compare the operative outcomes of LDLT and DDLT recipients. A literature search was performed to identify clinical controlled studies comparing LDLT and DDLT that were published before October 2013. Four perioperative outcomes [duration of the recipient operation (DRO), red blood cell (RBC) transfusion requirement, length of the hospital stay, and cold ischemia time (CIT)] and 5 postoperative complication outcomes (biliary complications, vascular complications, intra-abdominal bleeding, perioperative death, and retransplantation) were the main outcomes assessed. Nineteen studies with a total of 5450 patients were included in the meta-analysis. In comparison with DDLT, LDLT was associated with a significantly longer DRO and a shorter CIT. We found that biliary complications [odds ratio (OR) = 3.08, 95% confidence interval (CI) = 1.97-4.81, P < 0.001], vascular complications (OR = 2.16, 95% CI = 1.32-3.54, P = 0.002), and retransplantation (OR = 1.76, 95% CI = 1.09-2.83, P = 0.02) occurred more frequently for LDLT recipients, and the subgroup analysis indicated that the biliary complication rate decreased dramatically with greater LDLT experience. No significant difference was observed in RBC transfusion requirements, the lengths of hospital stays, intra-abdominal bleeding rates, or perioperative mortality between LDLT and DDLT recipients. In conclusion, LDLT is associated with a higher rate of surgical complications after transplantation. A reduction of postoperative complication rates can be achieved as centers gain greater experience with LDLT. However, LDLT is still an excellent alternative to DDLT because it facilitates access to LT.

(663) - Large Perioperative Red Blood Cell Transfusion Requirements Are Associated with Increased Long Term Mortality After LVAD Implantation

(663) - Large Perioperative Red Blood Cell Transfusion Requirements Are Associated with Increased Long Term Mortality After LVAD Implantation

Effect of erythropoiesis-stimulating agents on hemoglobin level, fatigue and hospitalization rate in renal palliative care patients

To investigate the effect of erythropoiesis-stimulating agents (ESAs) on hemoglobin (Hb) level, fatigue and hospitalization rate in renal palliative care (PC) patients. A retrospective cohort study was done between April 2011 and January 2013 in renal palliative care clinic of clustered hospitals in Hong Kong. The study participants included end-stage renal patients (CrCl < 15 ml/h) decided not for dialysis (ESA 39 patients; control 31 patients). From healthcare databases, we retrieved the patient demographics, laboratory results, reasons and time of hospitalizations during the study period. Fatigue was measured by Edmonton Symptom Assessment Scale. Most were elderly patients and about half of patients had underlying diabetes mellitus. Baseline mean Hb levels were similar (7.57 ± 0.97 g/dL for ESA vs 7.77 ± 0.72 g/dL for control). Mean Hb was raised significantly after 3 and 6 months of ESA injections (9.42 and 9.40 g/dL respectively, P < 0.05). Fatigue was reduced significantly at 3 and 6 months after treatment (P = 0.006 and P = 0.017 respectively). All-cause hospitalization was reduced significantly and there was a trend toward reduction in red blood cell transfusion requirement in the ESA group (P = 0.084). This study demonstrated that use of ESAs in renal PC was effective and might help in reducing fatigue and hospitalizations rate.

Predicting blood loss and transfusion requirement in patients undergoing surgery for musculoskeletal tumors

Few studies have systematically identified factors associated with blood loss in musculoskeletal tumor surgery. We aimed to identify risk factors for requiring large-volume transfusion in musculoskeletal tumor surgery and created an interactive model to predict red blood cell transfusion requirements based on patient characteristics. These data will facilitate planning in hospital blood banks and aid identification of specific groups for future interventions targeted at reducing blood utilization. Only one similar study has been published and there are minimal data surrounding interventions designed to minimize blood loss in musculoskeletal tumor surgery. We retrospectively analyzed a database containing 1322 consecutive surgeries, performed at a quaternary referral center in Melbourne, Australia. Using logistic regression analysis and a negative truncated binomial logistic regression model, we developed prediction models for transfusion requirement. The following factors were associated with large-volume transfusion: malignant tumors, bone tumors, sacral and pelvic tumors, high American Society of Anesthesiologists (ASA) score, and tumor size of more than 5 cm. High ASA score was also strongly associated with 30-day mortality. Preoperative planning in high-risk patients is critical to ensure adequate blood product supply, minimize wastage, and optimize the patient's general health before surgery. These patients would be ideal targets for future randomized studies aimed at reducing blood utilization.

Partial Cholecystectomy: A Technique That Makes Hilar Dissection Easier in Recipient Hepatectomy

BackgroundIntraoperative blood loss and red blood cell transfusion requirements have a negative impact on outcome after orthotopic liver transplantation. In this study we compared blood transfusion requirements, bile duct injury, and dissection of hepatic artery rates in the patients with or without partial cholecystectomy during recipient hepatectomy. MethodsFrom December 2008 to August 2011, 100 recipient hepatectomies were performed by the same surgeon. Patients were divided into 2 groups. The first group included patients with partial cholecystectomy, and the other group patients without partial cholecystectomy. Each group consisted of 50 patients. ResultsIn recipient hepatectomy group without partial cholecystectomy, intraoperative blood transfusions were in the range of 3–11 units (mean, 6.3 units). In this group there were 4 hepatic artery dissections and 2 bile duct injuries. In the group with partial cholecystectomy, intraoperative blood transfusions were in the range of 0–7 units (mean, 3.1 units). In this group there was 1 hepatic artery dissection. There were no operative mortalities in either group. ConclusionsWe recommend partial cholecystectomy during recipient hepatectomy of cirrhotic patients, particularly with hydropic gallbladders, because bleeding from the points of adherent gallbladder during mobilization of the liver is diminished and fewer artery dissections and bile duct injuries develop, because the procedure facilitates dissection of the hilar structures.

Impact of anti-aggregant, anti-coagulant and non-steroidal anti-inflammatory drugs on hospital outcomes in patients with peptic ulcer bleeding

Background/Aims:There are a limited number of studies including the impact of antiplatelet drugs use on hospital outcomes for nonvariceal upper gastrointestinal bleeding. The aim of this study was to determine the effect of anti-aggregant, anti-coagulant and non-steroidal anti-inflammatory drugs upon hospital outcomes in patients with peptic ulcer bleeding.Materials and Methods:The patients under treatment with antiaggregant, anticoagulant or non-steroidal anti-inflammatory drugs were categorized as exposed group (n = 118) and the patients who were not taking any of these drugs were categorized as non-exposed group (n = 81). We analyzed the data of drug intake, comorbid disease, blood transfusion, duration of hospital stay, Blatchford/total Rockall score and diagnosis of patients.Results:In total, 199 patients were included. Of these 59.3% (exposed group) were taking drugs. The patients in exposed group were significantly older than those in non-exposed group (62.9 ± 17.3 years; 55.5 ± 19.3 years, P = 0.005, respectively). Mean number of red blood cell units transfused (2.21 ± 1.51; 2.05 ± 1.87, P = 0.5), duration of hospital stay (3.46 ± 2.80 days; 3.20 ± 2.30 days, P = 0.532) and gastric ulcer rate (33% vs 23.4%, P = 0.172) were higher in exposed group than in non-exposed group but the differences were not statistically significant. Total Rockall and Blatchford scores of the patients were significantly higher in exposed group than in non-exposed group (3.46 ± 1.72 vs 2.94 ± 1.87, P = 0.045; 10.29 ± 3.15 vs 9.31 ± 3.40, P = 0.038).Conclusıon:Our study has shown that anticoagulants, antiaggregants and nonsteroidal anti-inflammatory drugs do not effect duration of hospital stay, red blood cell transfusion requirement and rebleeding for peptic ulcer bleeding.

Effectiveness of Tranexamic Acid in Reducing Blood Loss after Spinal Fusion

Purpose: Spinal fusion surgery can be associated with significant blood loss, often requiring blood transfusion. The objective of this retrospective study was to evaluate the efficacy of tranexamic acid in reducing blood loss and transfusion after lumbar spinal fusion. Materials and Methods: A total of 75 consecutive patients undergoing spinal fusion surgery for spinal stenosis were included in this study. Thirty-five patients who were administered tranexamic acid were compared with 40 patients who did not receive the drug. Blood loss through drain, amount of blood transfusion, and hematological laboratory findings were evaluated. Results: Blood loss through drain for the first 24 hours after surgery was 548.6±192.1 ml in the tranexamic acid group and 1,089.8±368.3 ml in the control group with a significant difference (p=0.001). Total blood loss through drain was 1,010.5±452.5 ml in the tranexamic acid group and 1,512.7±427.8 ml in the control group with a significant difference (p=0.005). Time to removal of drains after surgery was not different, 2.6±0.8 days in the tranexamic acid group and 2.5±1.1 days in the control group (p=0.885). Packed red blood cell (RBC) transfusion for the postoperative period and the number of patients requiring transfusion was significantly lower in the tranexamic acid group than in the control group. A prolongation of protrombin time was observed in the control group on first postoperative day. There were no complications related to the use of tranexamic acid. Conclusion: Tranexamic acid had an effect on reducing blood loss through drain for the first 24 hours and total blood loss after spinal fusion surgery. As a result, there was less of a requirement for RBC transfusion after surgery.

Refractory bleeding from intestinal angiodysplasias successfully treated with danazol in three patients with von Willebrand disease

von Willebrand disease (VWD) is associated with development of gastrointestinal (GI) vascular malformations that lead to chronic GI bleeding. Conventional management, including von Willebrand factor concentrate replacement and endoscopic ablation or bowel resection, does not consistently reduce hemorrhage. We describe three patients with VWD for whom conventional management failed to control GI bleeding. We retrospectively reviewed medical records of patients with VWD and GI bleeding. After patients began treatment with danazol, we observed long-term reductions in GI bleeding and packed red blood cell transfusion requirements. One patient had severe liver toxicity and was found to have concomitant primary biliary cirrhosis. Danazol use may be considered in patients with VWD and GI bleeding due to angiodysplasia that otherwise fails to respond to conventional treatment; the primary aim of treatment is to reduce transfusion dependence. The benefits are variable and possibly transient. Monitoring for toxicity is important when this treatment is pursued.

ABO Blood Group Mismatch Does Not Affect Survival Or Transfusion Requirements In Patients Undergoing Alemtuzumab-Based Reduced-Intensity Conditioned Hematopoietic Stem Cell Transplantation

AimsLimitations in donor availability require that ABO blood group incompatible donors are used for hematopoetic stem cell transplantation (HSCT). Previous studies on the influence of ABO mismatch on the outcomes of allogeneic HSCT show conflicting results, and suggest that the nature of peri-transplant immunosuppressive therapy may influence the impact of ABO mismatch. This study examined the impact of ABO blood group mismatch on transplant outcomes and transfusion requirements in a large UK HSCT cohort following reduced intensity conditioning (RIC) with alemtuzumab. MethodsConsecutive patients from three UK transplant centres (Birmingham, Glasgow, Oxford) undergoing first alemtuzumab-based RIC HSCT between 2000 and 2010 were included for analysis. Overall survival (OS), relapse-free survival (RFS), relapse incidence (RI), non-relapse mortality (NRM), incidence of acute and chronic graft-versus-host disease (GvHD) and red blood cell (RBC) and platelet (PLT) transfusion requirements were analyzed retrospectively according to the degree of ABO mismatch. ABO mismatch was defined as minor if anti-recipient isohemagglutinins were present in the donor, major if anti-donor isohemagglutinins were present in the recipient, and bidirectional if both anti-donor and anti-recipient isohemagglutinins were present. Results598 patients underwent alemtuzumab-based RIC HSCT between 2000 and 2010. The median recipient age was 51 (range 17-74) and 342/598 (57%) were male. 361/598 (60%) received stem cells from an HLA- matched unrelated donor. Patients were HLA matched to at least 6/6 in 569/598 (95%), 225/598 (38%) were matched to 10/10. The main indications for HSCT were acute myeloid leukaemia (194/598, 32%), non-Hodgkin's lymphoma (125/598, 21%) and myelodysplastic syndrome (76/598, 13%). Stem cells were sourced from peripheral blood in 548/598 (92%) and bone marrow in 50/598 (8%). The most frequently used conditioning regimen was fludarabine, melphalan and alemtuzumab in 459/598 (77%). Donor and recipient ABO blood groups were matched (M) in 318/598 (53%). Minor (MN) mismatch was present in 113/598 (19%), major (MJ) mismatch in 128/598 (21%), and bidirectional (BD) mismatch in 35/598 (6%).OS & RFS at 2 years did not significantly differ according to the degree of ABO mismatch (OS 51.9% M vs. 54.8% MN vs. 54.7% MJ vs. 38.6% BD; RFS 41.4% M vs. 42.5% MN vs. 50.2% MJ vs. 29.9% BD, p>0.05 for all), although recipients of a bidirectionally mismatched transplant showed a trend to reduced OS (p=0.078). 2 year RI & NRM was not significantly different by ABO mismatch (RI 29.6% M vs. 28.5% MN vs. 27.2% MJ vs. 29.4% BD; NRM 26.5% M vs. 26.1% MN vs 20.7% MJ vs 29.4% BD, p>0.05 for all). On multivariate analysis, ABO mismatch was not a significant predictor of OS, RFS, NRM or RI.The degree of ABO mismatch did not influence the incidence of grade 2-4 acute GvHD (incidence 19.6% M vs. 30.6% MN vs. 26.8% MJ vs. 31.9% BD). The incidence of extensive chronic GvHD, however, was significantly higher in patients with minor and major ABO mismatch on both univariate and multivariate analysis (14.1% M vs. 21.7% MN vs. 22.1% MJ vs. 14.2% BD; HR 1.74, p=0.032 for MN vs M, HR 1.69, p=0.0036 for MJ vs M).The proportion of patients requiring ≥1 unit red blood cell (RBC) transfusion support did not differ significantly by ABO match (91% M, 94% MN, 93% MJ, 85% BD, p > 0.05 when compared to M). A lower proportion of bidirectionally mismatched patients required ≥1 unit of platelets than the matched cohort (94% M, 78% BD, p=0.008 for BD vs. M, 91% MJ, 94% MN, p > 0.05 when compared to M).For those requiring transfusion, the median number of RBC and PLT units transfused to day 100 were not significantly different by ABO match (median (range) of RBC: 6 (2-66) M, 7 (1-43) MN, 7 (2-38) MJ, 6 (2-32) BD, p=0.157; median (range) of PLT: 4 (1-92) M, 4 (1-70) MN, 4 (1-46) MJ, 3.5 (1-33) BD; p=0.45). On multiple regression analysis, bidirectional mismatch was associated with fewer RBC transfusions (p=0.034). There was no significant effect of ABO match on PLT requirements. ConclusionThis is the largest series to date examining the effects of ABO matching in alemtuzumab-based RIC HSCT. Our data indicate that ABO mismatch in this setting has no clinically significant effect on transplant survival outcomes or on transfusion requirements, but may influence the incidence of extensive chronic GvHD. Disclosures:No relevant conflicts of interest to declare.

Iron Chelation Therapy Could Rapidly Reduce Oxidative DNA Damage In CD34+ Hematopoietic Cells Before Decrease Of Serum Ferritin Level

IntroductionMyelodysplastic syndrome (MDS) is characterized by dysplastic and ineffective hematopoiesis, peripheral blood cytopenias and a risk of leukemic transformation. Most MDS patients eventually require red blood cell (RBC) transfusions for anemia and consequently develop iron overload. Excess free iron in cells catalyzes generation of reactive oxygen species (ROS) especially hydroxyl radical that cause oxidative DNA damage including formation of mutagenic 8-hydroxy-2'-deoxyguanosine (8-OHdG) and DNA double strand breaks. However, it is unclear whether iron-mediated oxidative stress affects the pathophysiology of MDS. MethodsThis study included MDS patients who visited our university hospital and affiliated hospitals (n=43). Among them, 13 patients received iron chelation therapy when their serum ferritin (SF) level was greater than 1000 ng/mL or they required more than 20 RBC transfusions (or 100 mL/kg of RBC). We analyzed hemoglobin, SF level and chromosomal abnormality and 8-OHdG levels in peripheral blood mononuclear cells (PBMC) obtained from MDS patients before and after iron chelator, deferasirox administration. ResultsWe showed that reactive oxygen species (ROS) in hematopoietic cells was higher in MDS patients with high SF level. Furthermore, the 8-OHdG levels in MDS patients were significantly higher than those in healthy volunteers and the 8-OHdG levels were positively correlated with SF (p=0.003, r=0.495) and chromosomal abnormalities (p=0.019). Importantly, the 8-OHdG levels in PBMC and CD34+ cells of MDS patients dramatically decreased 3 month after deferasirox administration (the 8-OHdG levels in PBMC, 3.374±78, p<0.05) although SF level were not reduced within 3 month (Figure). However, SF level decreased to 500-600 ng/mL after 36 months of iron chelation therapy, 8-OHdG is a sensitive marker of cellular iron chelation therapy by deferasirox which readily passes through the plasma membrane. When patients were divided into the no Iron chelation group (n=10) and high Iron chelation group (n=13), the survival time was significantly longer in the latter group than the former group (P=0.046) although International prognostic scoring system (IPSS) was not significantly difference between both groups. Further, 50% of patients without iron chelation group developed into leukemia, while no patients did progress into leukemia during 36 month. [Display omitted] ConclusionThese results indicated that cellular excess iron could contribute to the pathophysiology of MDS and iron chelation therapy could improve the oxidative DNA damage in MDS patients. Disclosures:No relevant conflicts of interest to declare.

Bortezomib Is Highly Effective For Pure Red Cell Aplasia After ABO-Incompatible Hematopoietic Stem Cell Transplantation

Introduction Pure red cell aplasia (PRCA) is an uncommon complication of ABO-incompatible hematopoietic stem cell transplantation. It is characterized by anemia, reticulocytopenia and absence of erythroid precursors in a morphologically normal-appearing bone marrow. Most cases of PRCA resolve spontaneously within weeks to months. A small subset of patients has a protracted disease course requiring continued red blood cell (RBC) transfusions. There is no approved standard of care for PRCA. Tapering of immunosuppressives such as steroids and calcineurin inhibitors, plasma exchange, rituximab, and anti-thymocyte globulin have all been employed with varying success rates. We report a case of PRCA after ABO-incompatible transplant that responded remarkably to treatment with bortezomib. Case Presentation A 60 year old female received a non-myeloablative HLA-matched ABO-mismatched sibling donor transplant for lenalidomide-refractory myelodysplastic syndrome (5q-). She received fludarabine/busulfan conditioning and tacrolimus/methotrexate for GVHD prophylaxis. The donor was blood type A Rh-positive and the recipient was O Rh-positive. The patient's post-transplant course was complicated by delayed engraftment, thrombocytopenia and autoimmune hemolytic anemia. When seen at our institution 22 months post-transplant, she had transfusion-dependent anemia requiring RBC transfusions every 2-3 weeks and reticulocytopenia. Bone marrow biopsy showed erythroid aplasia and preserved hematopoiesis in other cell lines, dysplasia was absent and parvovirus testing was negative. The patient had evidence of complete engraftment based on short tandem repeat analysis. Blood typing reflected transfused type O Rh-negative RBCs. Neither A cells from the donor nor Rh-positive cells from the patient were detected. High titers of anti-A and anti-B isohemagglutinins were detected despite transfusion with washed RBCs to reduce passive transfer. She was treated with prednisone 60mg/day, rituximab 375 mg/m2 weekly x4 and methylprednisolone 1g weekly x6 without response. Eventually, all immunosuppressive medications were discontinued to induce a graft versus recipient response. Two subsequent bone marrow biopsies continued to show nearly absent erythropoiesis, and the rare erythroid cells present lacked the blood group A antigen. Since PRCA was thought to be due to the recipient's plasma cells making anti-A antibodies, bortezomib, a potent inducer of apoptosis in plasma cells, was initiated. Subcutaneous bortezomib 1.3 mg/m2 was administered weekly x4. The patient responded well to therapy. A month after completion of bortezomib, the patient's hemoglobin measured 12.1 g/dL, reticulocyte count was 174 x109/L and IgM and IgG anti-A titers were both &lt; 1. Bone marrow biopsy showed relative erythroid hyperplasia, and the majority of the erythroid precursors expressed blood group A. The patient continues to do well and at the time of her most recent evaluation, her hemoglobin was 13.9 g/dL. She has also remained transfusion-independent. Discussion PRCA after major ABO-incompatible transplant is thought to be caused by persistence of recipient plasma cells that continue to secrete anti-donor isohemagglutinins. Antibody titers may remain elevated for a longer duration in patients receiving non-myeloablative preparatory regimens. Bortezomib is a proteasome inhibitor that selectively induces apoptosis in plasma cells. Bortezomib has been used successfully to treat anti-body mediated rejection in both renal and liver transplant patients. A case of PRCA following ABO-mismatched hematopoietic transplant that was successfully treated with IV bortezomib has also been reported. To our knowledge, this is the first reported case of isohemagglutinin-mediated PRCA after ABO-mismatched transplant that responded favorably to subcutaneous bortezomib. Limitation The lack of long-term follow-up data precludes any assessment about the durability and persistence of response to bortezomib. Conclusion Bortezomib is an effective treatment for patients with PRCA mediated by residual host isohemeagglutinins after ABO-incompatible hematopoietic transplantation. Disclosures: Off Label Use: Our presentation describes the use of bortezomib for treatment of pure red cell aplasia after ABO-incompatible hematopoeitic stem cell transplantation. Vercellotti:Sangart Inc.: Research Funding; Seattle Genetics, Inc.: Research Funding.