BACKGROUND Some observational studies have reported that transfusion of red-cell units that have been stored for more than 2 to 3 weeks is associated with serious, even fatal, adverse events. Patients undergoingcardiac surgery may be especially vulnerable to the adverse effects of transfusion. METHODS We conducted a randomized trial at multiple sites from 2010 to 2014. Participants 12 years of age or older who were undergoing complex cardiac surgery and were likely to undergo transfusion of red cells were randomly assigned to receive leukocyte-reduced red cells stored for 10 days or less (shorter-term storage group) or for 21 days or more (longer-term storage group) for all intraoperative and postoperative transfusions. The primary outcome was the change in Multiple Organ Dysfunction Score (MODS; range, 0 to 24, with higher scores indicating more severe organ dysfunction) from the preoperative score to the highest composite score through day 7 or the time of death or discharge. RESULTS The median storage time of red-cell units provided to the 1098 participants who received red-cell transfusion was 7 days in the shorter-term storage group and 28 days in the longer-term storage group. The mean change in MODS was an increase of 8.5 and 8.7 points, respectively (95% confidence interval for the difference, −0.6 to 0.3; P = 0.44). The 7-day mortality was 2.8% in the shorter-term storage group and 2.0% in the longer-term storage group (P = 0.43); 28-day mortality was 4.4% and 5.3%, respectively (P = 0.57). Adverse events did not differ significantly between groups except that hyperbilirubinemia was more common in the longer-term storage group. CONCLUSIONS The duration of red-cell storage was not associated with significant differences in the change in MODS. We did not find that the transfusion of red cells stored for 10 days or less was superior to the transfusion of red cells stored for 21 days or more among patients 12 years of age or older who were undergoing complex cardiac surgery. (Funded by the National Heart, Lung, and Blood Institute; RECESS ClinicalTrials.gov number, NCT00991341.)

The question of whether storage of red blood cells (RBCs) alters their capacity to deliver oxygen and affects patient outcomes remains in a state of clinical equipoise. Studies of the changes which occur while RBC are stored have led to several physiologically plausible hypotheses that these changes impair RBC function when the units are transfused. Although there is some evidence of this effect in vivo from animal model experiments, the results of several largely retrospective patient studies have not been consistent. Some studies have shown an association between worse clinical outcomes and transfusion of RBC which have been stored for longer periods of time, while others have found no effect. Three multicenter, randomized, controlled trials have been developed to address this important, but currently unanswered, question. Two clinical trials, one in low birth weight neonates and the other in intensive care unit patients, are enrolling subjects in Canada (the Age of Red Blood Cells in Premature Infants; the Age of Blood Study). The third trial, which is being developed in the United States, is the Red Cell Storage Duration Study (RECESS). This is a multicenter, randomized, controlled trial in which patients undergoing complex cardiac surgical procedures who are likely to require RBC transfusion will be randomized to receive RBC units stored for either 10 or fewer days or 21 or more days. Randomization will only occur if the blood bank has enough units of RBC of both storage times to meet the crossmatch request; hence, subjects randomized to the ≥ 21 day arm will receive RBC of

BACKGROUNDPathogen inactivation (PI) is a new approach to blood safety that may introduce additional costs. This study identifies costs that could be eliminated, thereby mitigating the financial impact.STUDY DESIGN AND METHODSCost information was obtained from five institutions on tests and procedures (e.g., irradiation) currently performed, that could be eliminated. The impact of increased platelet (PLT) availability due to fewer testing losses, earlier entry into inventory, and fewer outdates with a 7-day shelf life were also estimated. Additional estimates include costs associated with managing 1) special requests and 2) test results, 3) quality control and proficiency testing, 4) equipment acquisition and maintenance, 5) replacement of units lost to positive tests, 6) seasonal or geographic testing, and 7) health department interactions.RESULTSAll costs are mean values per apheresis PLT unit in USD ($/unit). The estimated test costs that could be eliminated are $71.76/unit and a decrease in transfusion reactions corresponds to $2.70/unit. Avoiding new tests (e.g., Babesia and dengue) amounts to $41.80/unit. Elimination of irradiation saves $8.50/unit, while decreased outdating with 7-day storage can be amortized to $16.89/unit. Total potential costs saved with PI is $141.65/unit. Costs are influenced by a variety of factors specific to institutions such as testing practices and the location in which such costs are incurred and careful analysis should be performed. Additional benefits, not quantified, include retention of some currently deferred donors and scheduling flexibility due to 7-day storage.CONCLUSIONSWhile PI implementation will result in additional costs, there are also potential offsetting cost reductions, especially after 7-day storage licensing.

Bacterial and fungal infections continue to be a major problem in patients with prolonged severe neutropenia. Early controlled trials suggested that granulocyte transfusions were modestly effective in this setting, but the doses provided were later considered inadequate. Recent studies have shown that the dose can be increased substantially by administering G-CSF ± dexamethasone to granulocyte donors. Although these cells circulate in neutropenic recipients and appear to function normally, the evidence for clinical efficacy has been inconclusive. We report here the result of the RING study, a recently completed randomized controlled trial on the efficacy of high-dose granulocyte transfusion therapy, carried out as part of the NHLBI Transfusion Medicine/Hemostasis Clinical Trials Network. Fourteen clinical sites participated. Eligible subjects were those with neutropenia (ANC<500) and proven/probable/presumed bacterial or fungal infection. Subjects were randomized to receive either 1) standard antimicrobial therapy or 2) standard antimicrobial therapy plus daily granulocyte transfusions from normal donors stimulated with G-CSF (450µg) and dexamethasone (8mg). The primary end point was a composite one; survival plus a microbial response, both evaluated 42 days after randomization. Microbial response was determined by a blinded adjudication panel. The target sample size was 236 subjects, designed to provide 80% power to detect a 20% difference in success rates between treatment and control groups; however, only 114 subjects could be enrolled. Patient infections were 36% invasive fungal, 27% invasive bacterial, 11% fungemia, and 26% bacteremia. Subjects in both arms were well matched in terms of demographics, underlying disease, types and sites of infection, and severity of illness. Fifty six subjects were randomized to the granulocyte arm; 51 received at least one transfusion; the mean time from eligibility to the first transfusion was 2.3 +/- 1.2 days. Among these 51 subjects, the median number of transfusions was 5 (quartiles 3 and 9), given over a median of 6 days (quartiles 4 and 11). The median number of granulocytes administered per transfusion was 54.9 x109 (quartiles 26.1 x109, 72.5 x109). Fourteen percent of these patients had > Grade 3 hypoxemia develop during or within six hours after a granulocyte transfusion, requiring ventilation in one patient (2%). No deaths were attributed to adverse effects associated with the transfusions. Among subjects with sufficient data to determine the primary outcome, success rates were 42% (20/48) and 43% (21/49) for the granulocyte and control groups, respectively (p> 0.99) on Intention to Treat (ITT) analysis, and 49% (17/35) and 41% (16/39), respectively, for subjects who adhered to their assigned treatments (Per Protocol (PP) analysis)(p=0.64). There was also no significant difference between treatment groups in a model of the primary outcome that adjusted for baseline prognostic factors (e.g. ventilator use, high Zubrod score). Differences in primary end point success rates for granulocyte and control arms did not differ significantly for any infection type whether analyzed by ITT or PP. Outcomes for patients who received the first transfusion within 2 days of eligibility were similar to outcomes for patients who received the first transfusion later. For patients who received at least three granulocyte transfusions, those who received an average dose per transfusion of >50x109 granulocytes had a higher success rate (57.7%)(n=26) than those receiving <5x109 cells per transfusion (11.1%)(n=9)(p = 0.04); while supporting the hypothesis that dose is critical to the outcome, this result needs be interpreted with caution because of the low numbers and poor outcome of the low dose group. There was no significant difference between the granulocyte and control arms on overall survival to either 42 or 90 days after randomization. Because of incomplete patient enrollment, the power of this study to detect a 20% difference in overall success rates was reduced to approximately 40%. Thus it is possible that a true convincing favorable effect was missed, particularly, as suggested, in the subset of patients who received daily transfusions containing at least 50x109 granulocytes per transfusion. Disclosures Off Label Use: In the study being discussed, G-CSF is administered to normal blood donors. This is an off-label use of G-CSF. McCullough:Fresenius/Kabe: Membership on an entity's Board of Directors or advisory committees. Ness:Terumo BCT: Consultancy.

The overall cost of transfusion therapy is more influenced by the cost of the product than the cost of providing the transfusion. Depending on the cost adjustment by the supplier for different doses of PLTs, a low-dose transfusion strategy can be less costly.