Higher Red Blood Cell Transfusion Research Articles

Characteristics of red blood cell transfusion among very preterm infants in China.

National-level data on the incidence of red blood cell (RBC) transfusions and outcomes among very preterm infants (VPIs) are lacking in China. This study aims to describe the use and variation of RBC transfusion among VPIs in China. This cohort study was conducted among 70 tertiary hospitals participating in the Chinese Neonatal Network (CHNN) from 2019 to 2020 across China. All VPIs admitted to the CHNN neonatal intensive care units (NICUs) were included. A total of 13,447 VPIs were enrolled, of whom 7026 (52.2%) received ≥1 RBC transfusions. The mean number of transfusions per infant was 2 (interquartile range [IQR] 1-4 times) and the median age at first transfusion was 15 days (IQR 3-27 days). The transfusion rate was higher in critically ill infants compared with non-critically ill infants (70.5% vs. 39.3%). The transfusion rate varied widely (13.5%-95.0%) between different NICUs. The prevalence of death, severe intra-ventricular haemorrhage, necrotizing enterocolitis (NEC) or spontaneous intestinal perforation (SIP), sepsis, bronchopulmonary dysplasia (BPD), severe retinopathy of prematurity (ROP) and cystic periventricular leukomalacia (cPVL) was significantly higher in the transfused group. Among non-critically ill infants, RBC transfusion was independently associated with BPD, severe ROP and cPVL. Our study, providing the first baseline data on RBC transfusions among VPIs in China, shows an alarmingly high RBC transfusion rate with significant site variations. There is an urgent need for national guidelines on RBC transfusions for VPIs in China.

Impact of gender differences on hemostasis in patients after coronary artery bypass grafts surgeries in the context of tranexamic acid administration

BackgroundSex differences present in the blood management of patients after coronary artery bypass grafts (CABG) surgeries. Tranexamic acid (TXA) performed well in maintaining hemostasis during and after surgeries. However, the impact of sex differences on blood control after CABG in patients who received TXA was not investigated.MethodsOverall, 29,536 patients undergoing CABG with TXA administration from 2009 to 2019 in our hospital were included. Propensity score matching was performed. Finally, 6808 males and 6808 females were matched based on 23 covariates.ResultsFemale patients had a 0.36-fold lower incidence of reoperations due to major hemorrhage or cardiac tamponade compared to males (1.3% vs. 2.0%, p = 0.001, OR = 0.64, 95%CI = 0.49–0.84). Females had a median of 100 ml less blood loss in 24 h (median 360 vs. 460 ml, p < 0.0001), 150 ml less in 48 h (median 580 vs. 730 ml, p < 0.0001), and 180 ml less in total (median 760 vs. 940 ml, p < 0.0001) than male patients. The red blood cell (RBC) transfusion rate in female was 1.53-fold higher than that in male (33.0% vs. 21.6%, OR = 1.53, 95% CI = 1.43–1.63, p < 0.0001). Females also had higher morbidities than males after CABGs.ConclusionsFemales had less blood loss than males after CABG with the TXA treatment. Females still had a higher RBC transfusion rate after surgery. Morbidities in women were also higher than that in men.

Phase 1/2 Study of Oral TP-0184 for the Treatment of Anemia in Adults with Low- or Intermediate-Risk Myelodysplastic Syndromes

Patients with anemia due to lower-risk myelodysplastic syndromes (MDS) have limited treatment options. The transforming growth factor β (TGF-β) pathway has been implicated in contributing to ineffective hematopoiesis in patients with MDS. Members of the TGF-β superfamily include activin receptor-like kinase 2 (ALK2) and ALK5. ALK2 signaling plays a key role in modulating hepcidin, an important regulator of iron homeostasis (and thus erythropoiesis). Increased levels of hepcidin have been linked to anemia in patients with chronic inflammation and cancer, including multiple myeloma (Maes K, et al. Blood. 2010;116:3635-44). The role of hepcidin in MDS-related anemia is unknown and needs to be explored. ALK5 signaling through SMAD2/3 phosphorylation is constitutively active in bone marrow precursor cells from patients with MDS (Zhou L, et al. Blood. 2008;112:3434-43). Inhibition of ALK5 suppresses phosphorylation of SMAD2 in MDS hematopoietic progenitor cells and stimulates hematopoiesis in cells derived from patients with MDS. Collectively, these data suggest that blockade of the TGF-β-SMAD2/3 signaling pathway with an ALK5 inhibitor has the potential to benefit patients with anemia due to MDS.TP-0184 is a small-molecule, dual inhibitor of ALK2 and ALK5. In vitro, TP-0184 inhibits downstream signaling from ALK2 by reducing the phosphorylation of SMAD1/5/8 and blocks hepcidin expression (Peterson PW, et al. Blood. 2017;130 [suppl_1]: 937). Ex vivo, TP-0184 inhibits downstream signaling from ALK5 by reducing SMAD2/3 phosphorylation (data on file). By inhibiting both the ALK2 and ALK5 signaling pathways, TP-0184 may reduce ineffective erythropoiesis in patients with MDS.An open-label, single-arm, phase 1/2 study (NCT04623996) is being undertaken to evaluate the preliminary safety and efficacy of TP-0184 in treating anemia in adults (aged ≥18 years) with MDS. To be eligible, patients must have low- or intermediate-risk MDS (de novo or secondary) per the Revised International Prognostic Scoring System and have relapsed, exhibited an inadequate response to, or been refractory, resistant, or intolerant to treatment with an erythropoiesis-stimulating agent. Patients may have low or high red blood cell transfusion burden, must exhibit adequate major organ function, and must have an Eastern Cooperative Oncology Group performance status of 0-2. Key exclusion criteria include the presence of concomitant severe cardiovascular disease, such as congestive heart failure, myocardial infarction, angina, and/or uncontrolled cardiac arrhythmia; history of stroke, deep venous thrombosis, or pulmonary or arterial embolism; presence of clinically significant anemia due to iron, vitamin B12, or folate deficiencies, autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding; and prior allogeneic or autologous stem cell transplant.In this study, TP-0184 will be administered orally once daily for 24 weeks. The primary and secondary endpoints of each study phase are summarized in the table. Recruitment is ongoing, with approximately 30 patients targeted for enrollment in phase 1 and 10-60 patients targeted for enrollment in phase 2. In phase 1, increasing dose levels of TP-0184 ranging from 20 to 270 mg will be evaluated, with 1-6 patients dosed at each level. Dose escalation will be performed using a two-parameter Bayesian logistic regression model. Determination of the recommended phase 2 dose (RP2D) will be informed by the maximum tolerated or maximum administered dose in phase 1. In phase 2, the efficacy of TP-0184 at the RP2D will be monitored using Bayesian posterior probability to optimize enrollment with Bayesian stopping rules. Bayesian monitoring of responses will be started after the first 10 enrolled patients are evaluable for efficacy. [Display omitted] DisclosuresVerma: Medpacto: Research Funding; Curis: Research Funding; Eli Lilly: Research Funding; Stelexis: Consultancy, Current equity holder in publicly-traded company; Novartis: Consultancy; Acceleron: Consultancy; Celgene: Consultancy; Stelexis: Current equity holder in publicly-traded company; Throws Exception: Current equity holder in publicly-traded company; Incyte: Research Funding; GSK: Research Funding; BMS: Research Funding. Brunner: Celgene, Forty Seven Inc, Jazz: Other: Advisory Board; Novartis, Celgene, Takeda, AstraZeneca: Research Funding. Pennock: Sumitomo Dainippon Pharma Oncology, Inc: Current Employment. McMullen: Sumitomo Dainippon Pharma Oncology, Inc: Current Employment. Wade: Sumitomo Dainippon Pharma Oncology, Inc: Current Employment. Yang: Sumitomo Dainippon Pharma Oncology, Inc: Current Employment. Xie: Sumitomo Dainippon Pharma Oncology, Inc: Current Employment. Whatcott: Sumitomo Dainippon Pharma Oncology, Inc: Current Employment. Foulks: Sumitomo Dainippon Pharma Oncology, Inc: Current Employment. Melear: Janssen: Speakers Bureau; Astrazeneca: Speakers Bureau; TG Therapeutics: Speakers Bureau.

Risk factors for acute kidney injury after pediatric cardiac surgery: a meta-analysis.

Cardiac surgery-associated acute kidney injury (AKI) is associated with increased morbidity and mortality in both adults and children. This study aimed to identify clinical risk factors for AKI following cardiac surgery in the pediatric population. PubMed/MEDLINE, Embase, Scopus, and reference lists of relevant articles were searched for studies published by August 2020. Studies were included if (1) the population consisted of pediatric patients (< 18years old), (2) patients underwent cardiac surgery, (3) risk factors were compared between patients who developed AKI and those who did not, and (4) studies were prospective or retrospective observational studies or randomized controlled trials. Children undergoing pediatric cardiac surgery. Random-effects meta-analysis was performed, comparing potential risk factors between pediatric patients who developed CS-AKI and those who did not. Sixty-one publications including a total of 19,680 participants (AKI: 7257 participants; no AKI: 12,423 participants) were included from studies published between 2008 and 2020. The pooled estimated incidence of AKI was 34.3% (95% confidence interval 30.0-38.8%, I2 = 96.8%). Binary risk factors that were significantly and consistently associated with AKI were the presence of pulmonary hypertension, cyanotic heart disease, univentricular heart, risk adjustment for congenital heart surgery 1 (RACHS-1) score ≥ 3, vasopressor use, cardiopulmonary bypass use, reoperation, and sepsis. Significant continuous risk factors included younger age, lower body weight, lower preoperative creatinine, higher preoperative estimated glomerular filtration rate (eGFR), higher RACHS-1 score, longer surgery time, longer cardiopulmonary bypass time, longer aortic cross-clamp time, and higher red blood cell transfusion volume. Results are limited by heterogeneity and potential residual confounding. Our meta-analysis identified clinical risk factors that are associated with AKI in children undergoing cardiac surgery. This might help clinicians anticipate and manage more carefully this population and implement standardized preventive strategies. CRD42021262699. A higher resolution version of the Graphical abstract is available as Supplementary information.

Low Preoperative Antithrombin III Level Is Associated with Postoperative Acute Kidney Injury after Liver Transplantation

We aimed to determine the association between the preoperative antithrombin III (ATIII) level and postoperative acute kidney injury (AKI) after LT (post-LT AKI). We retrospectively evaluated 2395 LT recipients between 2010 and 2018 whose data of perioperative ATIII levels were available. Patients were divided into two groups based on the preoperative level of ATIII (ATIII < 50% vs. ATIII ≥ 50%). Multivariable regression analysis was performed to assess the risk factors for post-LT AKI. The mean preoperative ATIII levels were 30.2 ± 11.8% in the ATIII < 50% group and 67.2 ± 13.2% in the ATIII ≥ 50% group. The incidence of post-LT AKI was significantly lower in the ATIII ≥ 50% group compared to that in the ATIII < 50% group (54.7% vs. 75.5%, p < 0.001); odds ratio (OR, per 10% increase in ATIII level) 0.86, 95% confidence interval (CI) 0.81–0.92; p < 0.001. After a backward stepwise regression model, female sex, high body mass index, low albumin, deceased donor LT, longer duration of surgery, and high red blood cell transfusion remained significantly associated with post-LT AKI. A low preoperative ATIII level is associated with post-LT AKI, suggesting that preoperative ATIII might be a prognostic factor for predicting post-LT AKI.

What's New in Shock? January 2021.

What's New in Shock? January 2021.

Parvovirus B19 infection in sickle cell disease: An analysis from the Centers for Disease Control haemoglobinopathy blood surveillance project.

In the multicentre Haemoglobinopathy Blood Surveillance Project, to evaluate the seroprevalence of parvovirus B19 and DNA viral load in sickle cell disease (SCD). Although the epidemiology of parvovirus B19 seropositivity in SCD has been well documented, there are few studies that have assessed possible persistent parvovirus DNAemia and associated risk factors including blood transfusion. A qualitative analysis of parvovirus B19 serology using ELISA and quantitative parvovirus B19 DNA by RT-PCR was performed in patients with SCD. Of 322 patients, 113 (35%) were parvovirus IgG positive and 119 (37%) were IgM positive at enrolment. The prevalence of IgG positivity increased with age. 71/322 (22%) were parvovirus DNA positive at enrolment with a mean viral load of 15 227 ± 55 227 SD. (range 72-329 238 IU/mL). Patients who were positive for parvovirus B19 DNA received a significantly higher red blood cell transfusion volume in the prior year compared to patients who were negative (mean RBC volume = 8310 mL vs 5435 mL, respectively; P = .0073). Seventy-seven patients had follow-up testing approximately 1 year after enrolment and 11/28 (39%) patients had persistently positive IgM. Further studies are needed to better understand the natural history of parvovirus B19 infection in SCD especially in relation to RBC transfusion as a risk factor, as well as disease outcome and severity.

S838 TRANSFUSION DEPENDENCY IS ASSOCIATED WITH PRESENCE OF TOXIC IRON SPECIES AND INFERIOR SURVIVAL IN PATIENTS WITH LOWER-RISK MYELODYSPLASTIC SYNDROMES

Background: There are limited treatment options for red blood cell (RBC) transfusion dependent (TD) LR (IPSS Low/Int-1) MDS patients who are relapsed/refractory to ESAs. Imetelstat is a first-in-class telomerase inhibitor that targets cells with short telomeres and active telomerase, characteristics observed in some MDS patients across all disease stages. Preliminary results show that imetelstat is effective treatment in LR-MDS patients inducing durable TI (Steensma et al ASH 2018 Abstr463). Aims: We report updated efficacy data with a median follow-up of 12.1 months in 38 LR non-del(5q) MDS patients, R/R to ESA and LEN/HMA naive from the open-label, single-arm Part 1 of IMerge, an ongoing phase 2/3 study (NCT02598661). Methods: Part 1 of the IMerge study included patients with LR MDS, who were heavily transfused (≥4U/8wks), were R/R to ESA or had sEPO >500 mU/mL. Imetelstat 7.5 mg/kg was administered IV every 4 weeks. The primary endpoint was 8-week TI rate; key secondary endpoints included 24-week TI rate, safety, duration of TI, and hematologic improvement (HI) rate. Among the initially enrolled patients, higher 8-week TI rate was observed in the non-del5q, LEN/HMA naive patients. Therefore, the study was amended to subsequently enroll only these patients. From a total of 57 patients enrolled in Part 1, 38 were non-del(5q), LEN/HMA naïve patients (13 in the initial and 25 in the expansion cohort). Here we report long-term efficacy, safety and biomarker data from these 38 patients. Results: Median baseline RBC transfusion burden was 8U/8weeks (range 4–14), 37% of the patients had IPSS Int-1; 71% had WHO 2001 RARS or RCMD-RS subtype and 32% with evaluable sEPO levels had baseline level >500 mU/mL. As of 23 January 2019, median follow-up was 12.1 months for the 38 patients, representing 30.4 and 11.6 months for the initial 13 and additional 25 patients, respectively. The 8-week TI rate was 45% (17/38) and median TI duration was 8.5 months (range 1.8–32.4). Of the 17 responding patients, 10 (59%) remained transfusion free for over 24 weeks. The 8-week TI rate did not differ based on the presence of ring sideroblasts or baseline sEPO levels. The 24-week TI rate was 26% (10/38). Erythroid HI, defined as transfusion reduction by at least 4 units /8 weeks (IWG2006), was achieved in 68% (26/38) of the patients. The most frequently reported adverse events were manageable and reversible grade ≥3 cytopenias. 6/38 patients had IPSS-R intermediate/poor cytogenetic risk. All 6 patents achieved 8-week TI; 2/6 patients achieved partial cytogenetic response. Post treatment decrease in telomerase hTERT RNA level was observed in 25/34 (73.5%) patients with available sample. Among 7 patients with pre- and post-treatment mutation analyses, six had SF3B1 mutations at baseline, and a decrease in the mutation VAF was observed in 2 patients that had longest TI duration on study. Summary/Conclusion: In high RBC transfusion burden patients with non-del(5q) LR-MDS R/R to ESA and naive to LEN/HMA, single-agent imetelstat yielded 8-week TI rate of 45%, with a median duration of 8.5 months (range 1.8–32.4). The 24-week TI rate was 26%. HI-E rate was 68%. All patients with IPSS-R intermediate and poor cytogenetic risk responded. Biomarker analyses of telomerase activity and mutation allele burden indicate an effect on the malignant mutant clone. These data support Part 2 of IMerge, Phase 3 placebo-controlled, randomized portion of the study, expected to open mid-2019.

S837 TREATMENT WITH IMETELSTAT PROVIDES DURABLE TRANSFUSION INDEPENDENCE (TI) IN HEAVILY TRANSFUSED NON‐DEL(5Q) LOWER RISK MDS (LR‐MDS) RELAPSED/REFRACTORY (R/R) TO ERYTHROPOIESIS STIMULATING AGENTS (ESAS)

Background:There are limited treatment options for red blood cell (RBC) transfusion dependent (TD) LR (IPSS Low/Int‐1) MDS patients who are relapsed/refractory to ESAs. Imetelstat is a first‐in‐class telomerase inhibitor that targets cells with short telomeres and active telomerase, characteristics observed in some MDS patients across all disease stages. Preliminary results show that imetelstat is effective treatment in LR‐MDS patients inducing durable TI (Steensma et al ASH 2018 Abstr463).Aims:We report updated efficacy data with a median follow‐up of 12.1 months in 38 LR non‐del(5q) MDS patients, R/R to ESA and LEN/HMA naive from the open‐label, single‐arm Part 1 of IMerge, an ongoing phase 2/3 study (NCT02598661).Methods:Part 1 of the IMerge study included patients with LR MDS, who were heavily transfused (≥4U/8wks), were R/R to ESA or had sEPO &gt;500 mU/mL. Imetelstat 7.5 mg/kg was administered IV every 4 weeks. The primary endpoint was 8‐week TI rate; key secondary endpoints included 24‐week TI rate, safety, duration of TI, and hematologic improvement (HI) rate. Among the initially enrolled patients, higher 8‐week TI rate was observed in the non‐del5q, LEN/HMA naive patients. Therefore, the study was amended to subsequently enroll only these patients. From a total of 57 patients enrolled in Part 1, 38 were non‐del(5q), LEN/HMA naïve patients (13 in the initial and 25 in the expansion cohort). Here we report long‐term efficacy, safety and biomarker data from these 38 patients.Results:Median baseline RBC transfusion burden was 8U/8weeks (range 4–14), 37% of the patients had IPSS Int‐1; 71% had WHO 2001 RARS or RCMD‐RS subtype and 32% with evaluable sEPO levels had baseline level &gt;500 mU/mL.As of 23 January 2019, median follow‐up was 12.1 months for the 38 patients, representing 30.4 and 11.6 months for the initial 13 and additional 25 patients, respectively. The 8‐week TI rate was 45% (17/38) and median TI duration was 8.5 months (range 1.8–32.4). Of the 17 responding patients, 10 (59%) remained transfusion free for over 24 weeks. The 8‐week TI rate did not differ based on the presence of ring sideroblasts or baseline sEPO levels. The 24‐week TI rate was 26% (10/38). Erythroid HI, defined as transfusion reduction by at least 4 units /8 weeks (IWG2006), was achieved in 68% (26/38) of the patients. The most frequently reported adverse events were manageable and reversible grade ≥3 cytopenias. 6/38 patients had IPSS‐R intermediate/poor cytogenetic risk. All 6 patents achieved 8‐week TI; 2/6 patients achieved partial cytogenetic response. Post treatment decrease in telomerase hTERT RNA level was observed in 25/34 (73.5%) patients with available sample. Among 7 patients with pre‐ and post‐treatment mutation analyses, six had SF3B1 mutations at baseline, and a decrease in the mutation VAF was observed in 2 patients that had longest TI duration on study.Summary/Conclusion:In high RBC transfusion burden patients with non‐del(5q) LR‐MDS R/R to ESA and naive to LEN/HMA, single‐agent imetelstat yielded 8‐week TI rate of 45%, with a median duration of 8.5 months (range 1.8–32.4). The 24‐week TI rate was 26%. HI‐E rate was 68%. All patients with IPSS‐R intermediate and poor cytogenetic risk responded. Biomarker analyses of telomerase activity and mutation allele burden indicate an effect on the malignant mutant clone. These data support Part 2 of IMerge, Phase 3 placebo‐controlled, randomized portion of the study, expected to open mid‐2019.

Prophylactic Platelet Transfusions for Critically Ill Patients With Thrombocytopenia: A Single-Institution Propensity-Matched Cohort Study.

Thrombocytopenia is frequently encountered in critically ill patients, often resulting in prophylactic transfusion of platelets for the prevention of bleeding complications. However, the efficacy of this practice remains unclear. The objective of this study was to determine the relationship between prophylactic platelet transfusion and bleeding complications in critically ill patients. This is a retrospective cohort study of adults admitted to surgical, medical, or combined medical-surgical intensive care units (ICUs) at a single academic institution between January 1, 2009, and December 31, 2013. Inclusion criteria included age ≥18 years and a platelet count measured during ICU admission. Propensity-matched analyses were used to evaluate associations between prophylactic platelet transfusions and the outcomes of interest with a primary outcome of red blood cell transfusion in the ensuing 24 hours and secondary outcomes of ICU and hospital-free days and changes in sequential organ failure assessment scores. A total of 40,693 patients were included in the investigation with 3227 (7.9%) receiving a platelet transfusion and 1065 (33.0%) for which platelet transfusion was prophylactic in nature. In propensity-matched analyses, 994 patients with prophylactic platelet transfusion were matched to those without a transfusion. Patients receiving prophylactic platelets had significantly higher red blood cell transfusion rates (odds ratio 7.5 [5.9-9.5]; P < .001), fewer ICU-free days (mean [standard deviation] 20.8 [9.1] vs 22.7 [8.3] days; P = .004), fewer hospital-free days (13.0 [9.7] vs 15.8 [9.4] days; P < .001), and less improvement in sequential organ failure assessment scores (mean decrease of 0.2 [3.6] vs 1.8 [3.3]; P < .001) in the subsequent 24 hours. These findings appeared robust, persisting in multiple predefined sensitivity analyses. Prophylactic administration of platelets in the critically ill was not associated with improved clinical outcomes, though residual confounding may exist. Further investigation of platelet transfusion strategies in this population is warranted.

Severe and morbid obesity and transfusional risk in total knee arthroplasty: An observational study

BackgroundSevere and morbid obesity (Class II -III) represents a challenge for successful knee surgery. There isn't consensus on what influence body mass index has on blood loss and on red blood cell (RBC) transfusion during total knee arthroplasty (TKA). The objective was to determine blood loss and transfusion needs in severe and morbid obese patients undertaking TKA. MethodsWe recorded retrospectively all patients undergoing TKA. Obesity was assessed according to WHO guidelines. Perioperative haemoglobin and treatments for its optimisation were recorded. Blood losses were estimated from specific formulae for lost red-cell mass and percentage of lost blood volume. Results922 patients were included: 35.90% were obese Class I and 18.76% obese Class II - III. Estimated blood volume was 4390 ± 470 ml, 4736 ± 423 ml and 5030 ± 464 ml among non-obese, obese Class I and obese Class II-III, respectively (P < 0.001). The global estimated blood volume (EBV) lost was 1502 ± 680 ml without differences between the three groups. However, the percentage of lost blood volume was lower in obese Class II -III (29.65%) than in non-obese (33.55%) and obese Class I (30.97%) (P < 0.005). Transfusion rates were 12.7%, 12.1% and 6.4% for non-obese, obese Class I and Class II -III, respectively (P = 0.062). A negative transfusion risk was predicted for Class II -III patients. ConclusionsSeverely and morbidly obese patients did not show greater blood loss nor higher RBC transfusion needs after primary TKA than non-obese and obese Class I patients. This could be because obese Class II -III patients had higher EBV but similar RBC losses.

Improved Approach With Subcostal Exchange of the HeartMate II Left Ventricular Assist Device: Difference in On and Off Pump?

The HeartMate II (St. Jude Medical, Inc, St. Paul, MN [previously Thoratec]) left ventricular assist device (LVAD) exchange has traditionally involved a redo sternotomy. Alternate minimally invasive subcostal approaches have the advantage of avoiding sternal reentry, excessive bleeding, and prolonged recovery. This retrospective review included patients who underwent an exchange from May 2009 to March 2016. The patients were divided into three cohorts: (1) redo sternotomy, (2) subcostal approach involving cardiopulmonary bypass (CPB) (ON-CPB SC), and (3) subcostal approach off the CPB pump (OFF-CPB SC). Data pertaining to patients' baseline characteristics and outcomes were collected and analyzed. From May 1, 2009 to July 31, 2016, 33 HeartMate II LVAD exchanges were performed. There were 11 redo sternotomies and 22 subcostal exchanges, 12 of which were in the OFF-CPB SC group. There was no significant difference among the groups in terms of age (p= 0.75), sex (p= 0.95), and indication for exchange (p= 0.94). There was a higher red blood cell transfusion requirement within the sternotomy cohort (p < 0.001). The median time to extubation and the intensive care unit length of stay were significantly shorter in the OFF-CPB SC group (1 and 2.5 days, respectively) than in the sternotomy (2.5 and 21 day, respectively) and ON-CPB SC groups (1.5 and 5 days, respectively). The 30-day and 90-day survival rates were equivalent among the cohorts. Exchange of the HeartMate II LVAD can be accomplished with significantly improved recovery time and transfusion requirement through a less invasive subcostal approach when compared with sternotomy. The subcostal approach can be performed safely both on and off cardiopulmonary bypass.

Subnormal Lymphocyte Count Predicts Inferior Survival in Myelodysplastic Syndromes: A Single Center Experience in 889 Patients

▪BackgroundIn myelodysplastic syndromes (MDS), we have previously shown the adverse prognostic effect of ALC <1.2 x 10(9)/L (Nisha et al. Am J Hematol 2010;85:160). In the current larger study of 889 patients with MDS, we sought to validate and expand on our previous observations and also examine the effect of lymphocyte-to-monocyte ratio (LMR).MethodsWe retrospectively recruited 889 consecutive patients with primary MDS who were untreated at the time of referral to our institution, and in whom ALC and absolute monocyte count (AMC) at time of referral was documented. The diagnosis of MDS and leukemic transformation (LT) was according to WHO criteria (Blood. 2009;114:937). Complete follow-up information was updated in January 2015. Comparison of laboratory and clinical features was made between patients with subnormal and normal ALC; patients with above normal ALC were considered separately. Overall and leukemia-free survivals of patients with normal ALC was compared to those with either subnormal ALC or, in order to validate our previous observation, with ALC <1.2 x 10(9)/L.ResultsPatient characteristics:Median (range) values for the 889 study patients (69% males) included: age 72 (18-98), hemoglobin 9.6 g/dL (5.4-15.7), leukocyte count 3.4 x 10(9)/L (0.4-35), AMC 0.2 x 10(9)/L (0-1.7), platelet count 106 x 10(9)/L (2-1804), circulating blasts 0% (0-18) and bone marrow blasts 3% (0-19). Transfusion need was documented in 33% of patients and abnormal karyotype in 49%. Risk stratification by the revised international prognostic scoring system (IPSS-R) was very high in 10%, high in 16%, intermediate in 20%, low in 36% and very low in 16%. The median (range) ALC for the entire study population of 889 patients was 1.16 x 10(9)/L (0.02-8.9). The normal range of ALC at our institution was 0.9-2.9 x 10(9)/L; the number of patients with subnormal, normal and above normal ALC was 261 (29%), 598 (67%) and 30 (4%), respectively. In addition, 442 (50%) and 417 (47%) patients had ALC below 1.2 x 10(9)/L and ALC between 1.2 and the upper limit of normal, respectively. After a median follow-up of 27 months, 712 (80%) deaths and 116 (13%) leukemic transformations were documented.Comparison of patients stratified by absolute lymphocyte countCompared to patients with normal ALC, patients with subnormal ALC displayed lower hemoglobin (p=0.002), higher red blood cell transfusion need (p=0.0003), lower leukocyte count (p<0.0001), lower monocyte count (p=0.002) and lower platelet count (p<0.0001), whereas borderline association was also apparent for older age (p=0.06). In univariate analysis, survival was adversely affected by lower ALC, treated as a continuous variable (p=0.01). Similarly, when compared to patients with normal ALC, patients with subnormal ALC (p=0.001; HR 1.3, 95% CI 1.1-1.5) and those with ALC <1.2 x 10(9)/L (p=0.0002; HR 1.3, 95% CI 1.2-1.6) experienced significantly shortened survival. There was no difference in survival between patients with above normal ALC and those with either subnormal (p=0.58) or normal (p=0.41) ALC; accordingly, patients with above normal ALC were excluded from subsequent analysis.In multivariable analysis, the adverse effect of subnormal ALC was shown to be independent of age, gender, anemia, thrombocytopenia, neutropenia , circulating blast percentage, bone marrow blast percentage or cytogenetic risk stratification by and IPSS; the same held true for ALC <1.2 x 10(9)/L. The association with IPSS-R was of borderline significance for both ALC <1.2 x 10(9)/L (p=0.06) and subnormal ALC (p=0.1). The adverse effect of ALC was most apparent in patients with very low or low risk disease per IPSS-R (p=0.0007 for subnormal ALC and 0.0003 for ALC <1.2 x 10(9)/L), compared to those with higher risk status (p=0.67 and 0.7, respectively). Neither subnormal ALC (p=0.4) nor ALC <1.2 x 10(9)/L (p=0.1) affected leukemia free survival. Analysis using LMR in place of ALC showed similar but not necessarily superior results.ConclusionsCompared to those with normal ALC, MDS patients with either subnormal ALC or with ALC below 1.2 x 10(9)/L experienced shorter overall, but not leukemia-free, survival; this adverse effect was most apparent in lower risk patients and was independent of most of the currently established risk factors for survival in MDS. The observations from the current study suggest the possible therapeutic value of augmenting host immunity in lower risk MDS. DisclosuresAl-Kali:Onconova Therapeutics, Inc.: Research Funding; Celgene: Research Funding.

Effect of Pre-Transplant Red-cell Transfusion Events on Transplant Related Mortality and Overall Survival in Children with Leukemia Undergoing Hematopoietic Stem Cell Transplant

Background: Recent studies have shown that an elevated ferritin level prior to hematopoietic stem cell transplant (HSCT), serving as a surrogate marker of body iron load, is independently associated with transplant related mortality (TRM) and inferior overall survival (OS) in adult oncology patients. Study Design and Methods: We performed a retrospective cohort study of 112 children with leukemia treated at our institution over a 10 year period, and compared TRM and OS after HSCT in those children with and without high red-blood cell (RBC) transfusions. Both groups were similar in regards to age, diagnoses, donor type (matched related, matched unrelated, mismatched related, mismatched unrelated), stem cell source (peripheral blood, umbilical cord, bone marrow), baseline liver, cardiac and renal function, and median follow-up time. However, more children in the low RBC transfusion event cohort had high Karnofsky/Lansky performance scores (83.5% vs 54.5%, p=0.001) and fewer had recurrent leukemia or other forms of advanced disease compared with the children more heavily transfused (41.8% vs 87.9%, p<0.0001). Results: No association was observed between high RBC transfusion exposure and TRM. High RBC transfusion events were associated with lower OS at 5 years in univariate analysis (38% versus 61%, p=0.04); in multivariate analysis, this association was not significant (hazard ratio=1.3, 95% confidence interval 0.7-2.5). Conclusion: Further studies in children are needed to investigate iron overload and HSCT outcomes.

Classic Whipple versus pylorus-preserving pancreaticoduodenectomy in the ACS NSQIP

BackgroundThe classic Whipple operation carries substantial risk of complications. A pylorus-preserving pancreaticoduodenectomy might confer the benefit of decreased perioperative morbidity, but existing data comparing both techniques are inconclusive. MethodsUsing a propensity score model to adjust for potentially confounding differences in patient characteristics, 30-d mortality, operative time, red blood cell transfusion requirements, major complications, and length of hospital stay were compared between both techniques in the American College of Surgeons' National Surgical Quality Improvement Program database. Separate analyses were carried out for underlying malignancy or benign disease, as defined by International Classification of Diseases, Ninth Revision codes. ResultsA total of 6988 pancreaticoduodenectomies from 2005 through 2010 were included. In 5424 patients (77.6%) with underlying malignancy, there were no significant differences for 30-d mortality (2.4% versus 2.8%, P = 0.33) and major organ system complications (all P > 0.10). Patients undergoing the classic Whipple operation had a significantly longer operative time (389 versus 366 min, P < 0.01), longer length of hospital stay (13.1 versus 12.0 days, P < 0.01), and higher red blood cell transfusion requirements (1.0 versus 0.8 units, P < 0.01). Results were similar for 1564 patients (22.4%) with underlying benign disease, except for a higher occurrence of postoperative pulmonary (P = 0.02) and renal (P = 0.05) complications in patients undergoing the classic Whipple operation. ConclusionsShort-term outcomes after classic and pylorus-preserving pancreaticoduodenectomy in this large, multicenter database are excellent, without significant differences in postoperative mortality and most major organ system complications. However, small advantages in resource and blood utilization may be accomplished with the pylorus-preserving technique.

Restrictive Versus Liberal Red Blood Cell Transfusion Strategies for Preterm Infants: A Systematic Review of Randomized Controlled Trials

Background: Many neonatal intensive care units have introduced restrictive transfusion policies for preterm infants. The justification for such an approach is debatable. Objective: To systematically review the evidence from randomized controlled trials (RCTs) on the benefit to risk ratio of lower versus higher red blood cell transfusion thresholds in preterm infants. Methods: Systematic review based on an electronic literature search (09/2007) in PubMed and CENTRAL (Cochrane Library, Issue 3 2007) for RCTs on different transfusion strategies in preterm infants. Results: Seven fully published RCTs including 712 preterm infants with various gestational and postnatal ages were found to be eligible for inclusion in this systematic review. Transfusion thresholds differed between trials, as did the duration of studies, the reported outcomes and the methodological quality. The largest RCT included 451 Extremely-Low-Birth- Weight (ELBW) infants, was of high methodological quality and found no difference in reducing mortality before discharge home or survival with any of either severe retinopathy of prematurity, bronchopulmonary dysplasia or brain injury. Conclusions: Clinical and methodological heterogeneity between studies prevents firm conclusions based on the totality of available evidence. According to the results of the largest RCT, maintaining a higher hemoglobin level in ELBW infants seems to confer little clinical benefit. Keywords: Systematic review, preterm infants, transfusion threshold, restrictive, liberal