Efficacy of transfusion with granulocytes from G-CSF/dexamethasone–treated donors in neutropenic patients with infection

High-dose granulocyte transfusion therapy has been available for 20 years, yet its clinical efficacy has never been conclusively demonstrated. We report here the results of RING (Resolving Infection in Neutropenia with Granulocytes), a multicenter randomized controlled trial designed to address this question. Eligible subjects were those with neutropenia (absolute neutrophil count <500/μL) and proven/probable/presumed infection. Subjects were randomized to receive either (1) standard antimicrobial therapy or (2) standard antimicrobial therapy plus daily granulocyte transfusions from donors stimulated with granulocyte colony-stimulating factor (G-CSF) and dexamethasone. The primary end point was a composite of survival plus microbial response, at 42 days after randomization. Microbial response was determined by a blinded adjudication panel. Fifty-six subjects were randomized to the granulocyte arm and 58 to the control arm. Transfused subjects received a median of 5 transfusions. Mean transfusion dose was 54.9 × 109 granulocytes. Overall success rates were 42% and 43% for the granulocyte and control groups, respectively (P > .99), and 49% and 41%, respectively, for subjects who received their assigned treatments (P = .64). Success rates for granulocyte and control arms did not differ within any infection type. In a post hoc analysis, subjects who received an average dose per transfusion of ≥0.6 × 109 granulocytes per kilogram tended to have better outcomes than those receiving a lower dose. In conclusion, there was no overall effect of granulocyte transfusion on the primary outcome, but because enrollment was half that planned, power to detect a true beneficial effect was low (read more)

No evidence of transmission of chronic lymphocytic leukemia through blood transfusion

Monoclonal B-cell lymphocytosis (MBL) is a precursor of chronic lymphocytic leukemia (CLL). Observations of MBL in blood donors raise concern that transmitted MBL may cause recipient CLL. Using a database with health information on 1.5 million donors and 2.1 million recipients, we compared CLL occurrence among 7413 recipients of blood from 796 donors diagnosed with CLL after donation cessation, and among 80 431 recipients of blood from 7477 matched CLL-free donors. During follow-up, 12 and 107 cases of CLL occurred among the exposed and unexposed recipients, respectively, yielding a relative risk of 0.94 (95% confidence interval, 0.52-1.71). Analyses using the entire database showed no evidence of CLL clustering among recipients of blood from individual donors. In conclusion, when donor MBL was approximated by subsequent donor CLL diagnosis, data from 2 countries’ entire computerized transfusion experience over more than 30 years indicate that MBL/CLL transmission does not contribute importantly to recipient CLL risk (read more)

Exposure to ABO-nonidentical blood associated with increased in-hospital mortality in patients with group A blood

BACKGROUND : Transfusing ABO-compatible blood avoids most acute hemolytic reactions, but donor units that are ABO compatible are not necessarily ABO identical. Emerging data have raised concerns that ABO-nonidentical blood products lead to adverse outcomes.
STUDY DESIGN AND METHODS : A large multihospital registry (Transfusion Registry for Utilization, Surveillance, and Tracking) was used to determine the association between exposure to ABO-nonidentical blood and in-hospital mortality. Cox regression analyses controlled for sex, age, hemoglobin, creatinine, and in-hospital interventions and stratified by age of blood and admission year.
RESULTS : Data from 18,843 non–group O patients admitted between 2002 and 2011 and receiving at least 1 unit of blood were analyzed. Overall, group A patients had significantly increased risk of in-hospital death upon receiving a nonidentical unit (RR , 1.79; 95% CI, 1.20-2.67; p = 0.005). There was no evidence of increased risk for group B or AB patients. Similar results were seen when only patients with circulatory disorders were considered. When patients with injury or poisoning were excluded, both group A and B patients had significantly increased risk of in-hospital death.
CONCLUSION : Our study demonstrates an adverse effect of ABO-nonidentical blood in a broad range of patients with group A blood, after adjustment for potential confounders. Further research in this area is required to study possible mechanisms. Increased mortality associated with exposure to nonidentical blood in these patients would have a substantial impact at the population level; it would challenge how blood suppliers manage inventory and recruit donors and how health care providers administer blood (read more and editorial).

Variable HLA expression on deceased donor lymphocytes: Not all crossmatches are created equal

Flow cytometric crossmatch tests are used to detect donor-specific antibody and determine eligibility for transplantation. Crossmatch sensitivity is dependent on lymphocyte quality, to include HLA expression on the cell surface. The impact of HLA expression variability on crossmatch reactivity was examined using lymphocytes isolated from different donor types: deceased donor (DD) versus living donor (LD) and tissue sources (blood, spleen, or lymph nodes). HLA class I expression was similar on B cells isolated from LD blood, DD spleen, and DD lymph nodes, but significantly lower on B cells isolated from DD blood (p=0.0004). In contrast, class II expression on B cells and class I on T cells were significantly higher in LD blood than all DD tissues. Within DD tissues, spleen provided the highest expression of class II on B cells and class I on T cells. HLA expression on B cells, but not T cells, was impacted by memory (CD27+) versus non-memory status. Importantly, HLA expression differences on lymphocytes isolated from the same donor but different tissues impacted crossmatch outcomes. HLA expression is impacted by multiple factors and should be routinely monitored to ensure crossmatch sensitivity and to reconcile crossmatch strength with solid phase HLA antibody analyses (read more)

Survival after ultramassive transfusion: a review of 1360 cases

BACKGROUND : Information about patient survival after transfusion of multiple blood volumes is limited, and most reports have focused on trauma patients.
STUDY DESIGN AND METHODS : Retrospective study of blood use and survival at 11 hospitals in six nations between 2009 and 2013. Ultramassive transfusion (UMT) was defined as transfusion of 20 or more red blood cell (RBC) units over the course of any 2 consecutive calendar days.
RESULTS : A total of 1975 patients received UMT and a representative sample of 1360 patients was studied in detail. Patients were grouped into seven diagnostic categories: solid organ transplantation (n = 411), cardiac or major vascular surgery (n = 317), general surgery (n = 228), trauma (n = 221), general medicine (n = 124), obstetrics (n = 23), and other (n = 36). During the 7 days after initiation of UMT, these patients used more than 120,000 blood components. The median (interquartile range) blood use was 35 (26-50) RBC units, 30 (20-47) plasma units, and 7 (4-13) platelet doses. Five- and 30-day survival significantly declined with increasing RBC use. Overall survivals of patients receiving UMT were 71% (5 day) and 60% (30 day), and in the subset of 165 patients receiving 60 or more RBC units over 2 consecutive days, 5-day survival was 54% ranging from 17% (trauma) to 75% (solid organ transplant). The decline in survival with increasing RBC transfusions was minimal for patients undergoing solid organ transplantation and was most pronounced for trauma and nonsurgical bleeding patients.
CONCLUSION : Trauma was not the leading cause of UMT. Increasing RBC requirements were significantly associated with decreasing survival. However, survival was more strongly associated with diagnostic category than total RBCs transfused, with highest survival rates in solid organ transplant surgery (read more).

Platelets made HLA deficient by acid treatment aggregate normally and escape destruction by complement and phagocytes in the presence of HLA antibodies

BACKGROUND : The presence of antibodies against HLA Class I can lead to platelet (PLT) transfusion refractoriness, that is, the repeated failure to achieve adequate posttransfusion PLT count increments. PLT refractoriness can be overcome by transfusion of HLA-matched donor PLTs. A different approach is to remove HLA from the PLT surface using low pH. Previous case studies using HLA-stripped PLTs showed encouraging but inconsistent results and lacked information on the biologic effects of acid treatment on PLT function as well as sensitivity to PLT destruction in the presence of HLA antibodies.
STUDY DESIGN AND METHODS : PLTs prepared from buffy coats were stripped from HLA Class I using a brief incubation at pH 2.9. Kinetics of acid stripping, viability, phenotypic alterations, and sensitivity to complement-mediated lysis and phagocytosis were determined by flow cytometry. Functional potential was evaluated using a multiplate analyzer.
RESULTS : Acid-treated PLTs were viable, upregulated activation markers normally and aggregated to a similar extent as untreated PLTs in response to stimulation with three natural agonists. Acid treatment removed 70% to 90% of HLA Class I complexes from the PLT surface, which led to complete protection from HLA antibody–mediated complement lysis and reduced monocyte-mediated phagocytosis in the presence of anti-HLA in vitro.
CONCLUSION : Our study fills an important knowledge gap in how acid treatment affects PLT function and interactions with immune cells, paving the way for controlled clinical trials to evaluate acid-treated PLTs as an alternative to HLA-matched donors in PLT refractoriness (read more)