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BACKGROUND Two noninferiority, randomized, controlled trials were conducted in parallel comparing the safety and efficacy of platelets treated with Intercept or Mirasol pathogen-reduction technologies versus standard platelets. STUDY DESIGN AND METHODS The primary endpoint was the percentage of hematology patients who developed World Health Organization Grade 2 or greater bleeding. A noninferiority margin of 11% was chosen based on expected Grade 2 or greater bleeding in 20% of controls. The study was closed for financial restrictions before reaching the planned sample size of 828 patients, and an intention-to-treat analysis was conducted on 424 evaluable patients. RESULTS In the Intercept trial (113 treated vs. 115 control patients), the absolute risk difference in Grade 2 or greater bleeding was 6.1%, with an upper one-sided 97.5% confidence limit of 19.2%. The absolute risk difference in the Mirasol trial (99 treated vs. 97 control patients) was 4.1%, and the upper one-sided 97.5% confidence limit was 18.4%. Neither absolute risk difference was statistically significant. In both trials, posttransfusion platelet count increments were significantly lower in treated versus control patients. Mean blood component use in treated patients versus controls was 54% higher (95% confidence interval, 36%-74%; Intercept) and 34% higher (95% confidence interval, 16%-54%; Mirasol) for platelets and 23% higher (95% confidence interval, 8%-39%; Intercept) and 32% higher (95% confidence interval, 10%-57%; Mirasol) for red blood cells. Unexpected reactions and adverse events were not reported. Mortality did not differ significantly between treated and control patients. CONCLUSION Although conclusions on noninferiority could not be drawn due to low statistical power, the study provides additional information on the safety and efficacy of pathogen-reduced platelets treated with two commercial pathogen-reduction technologies.

The in vitro production of red blood cells and platelets is a groundbreaking technology that can—when optimized—surrogate for donated blood cells, in total or in part. Here we discuss questions that may arise when the technology is available, relative to safety issues (comprising both quantitative and qualitative parameters) and to ethics, an item often forgotten in the debates so far.

BACKGROUND Techniques for banking cord blood units (CBUs) as source for hematopoietic stem cell transplantation have been developed over the past 20 years, aimed to improve laboratory efficiency without altering the biologic properties of the graft. A large-scale, registry-based assessment of the impact of the banking variables on the clinical outcome is currently missing. STUDY DESIGN AND METHODS A total of 677 single cord blood transplants (CBTs) carried out for acute leukemia in complete remission in centers affiliated with the European Society for Blood and Marrow Transplantation were selected. An extensive set of data concerning CBU banking were collected and correlations with clinical outcome were assessed. Clinical endpoints were transplant-related mortality, engraftment, and graft-versus-host disease (GVHD). RESULTS The median time between collection and CBT was 4.1 years (range, 0.2-16.3 years). Volume reduction (VR) of CBUs before freezing was performed in 59.2% of available reports; in half of these the frozen volume was less than 30 mL. Cumulative incidences of neutrophil engraftment on Day 60, 100-day acute GVHD (II-IV), and 4-year chronic GVHD were 87, 29, and 21 ± 2%. The cumulative incidence of nonrelapse mortality (NRM) at 100 days and 4-year NRM were, respectively, 16 ± 2 and 30 ± 2%. Neither the variables related to banking procedures nor the interval between collection and CBT influenced the clinical outcome. CONCLUSION These findings indicate a satisfactory validation of the techniques associated with CBU VR across the banks. Cell viability assessment varied among the banks, suggesting that efforts to improve the standardization of CBU quality controls are needed.

Human T-cell leukemia viruses (HTLV-1 and HTLV-2) are associated with a variety of human diseases, including some severe ones. Transfusion transmission of HTLV through cellular blood components is undeniable. HTLV screening of blood donations became mandatory in different countries to improve the safety of blood supplies. In Japan and Europe, most HTLV-infected donors are HTLV-1 positive, whereas in the United States a higher prevalence of HTLV-2 is reported. Many industrialized countries have also introduced universal leukoreduction of blood components, and pathogen inactivation technologies might be another effective preventive strategy, especially if and when generalized to all blood cellular products. Considering all measures available to minimize HTLV blood transmission, the question is what would be the most suitable and cost-effective strategy to ensure a high level of blood safety regarding these viruses, considering that there is no solution that can be deemed optimal for all countries.

Two noninferiority, randomized, controlled trials were conducted in parallel comparing the safety and efficacy of platelets treated with Intercept or Mirasol pathogen-reduction technologies versus standard platelets.The primary endpoint was the percentage of hematology patients who developed World Health Organization Grade 2 or greater bleeding. A noninferiority margin of 11% was chosen based on expected Grade 2 or greater bleeding in 20% of controls. The study was closed for financial restrictions before reaching the planned sample size of 828 patients, and an intention-to-treat analysis was conducted on 424 evaluable patients.In the Intercept trial (113 treated vs. 115 control patients), the absolute risk difference in Grade 2 or greater bleeding was 6.1%, with an upper one-sided 97.5% confidence limit of 19.2%. The absolute risk difference in the Mirasol trial (99 treated vs. 97 control patients) was 4.1%, and the upper one-sided 97.5% confidence limit was 18.4%. Neither absolute risk difference was statistically significant. In both trials, posttransfusion platelet count increments were significantly lower in treated versus control patients. Mean blood component use in treated patients versus controls was 54% higher (95% confidence interval, 36%-74%; Intercept) and 34% higher (95% confidence interval, 16%-54%; Mirasol) for platelets and 23% higher (95% confidence interval, 8%-39%; Intercept) and 32% higher (95% confidence interval, 10%-57%; Mirasol) for red blood cells. Unexpected reactions and adverse events were not reported. Mortality did not differ significantly between treated and control patients.Although conclusions on noninferiority could not be drawn due to low statistical power, the study provides additional information on the safety and efficacy of pathogen-reduced platelets treated with two commercial pathogen-reduction technologies.

Donor history questionnaires for the determination of blood donor eligibility are a critical layer of blood safety. Early in the course of the AIDS epidemic in North America homosexual men with multiple partners were identified as one of the segments of the population with the highest risk of infection. Voluntary deferral of this group from blood donation led to a dramatic decrease in transfusion-transmitted HIV even before testing was introduced. In the early 1980s blood donors were deferred in England, the US and other nations, if they were ‘homosexual males with multiple partners’. After the implementation of HIV testing in 1985, the majority of the HIV-positive donors identified revealed ‘men having sex with men’ (MSM) behavior, leading the US Food and Drug Administration (FDA) to recommend indefinite deferral of all men who ‘have had sex with men, even once since 1977’; many other regulators and jurisdictions have enacted similar criteria. Three decades later, despite the recognition of other modes of transmission, MSM donors are still among the population segments with the highest prevalence and incidence of HIV in countries around the world. No other donor eligibility criterion has generated as much controversy or public discourse [1,2]. Proponents for change point out that in many countries other key components of blood safety such as donor testing and blood center process control have improved vastly, reducing the contribution of donor questioning to safety. Gay advocates in particular argue that donor selection policies based on MSM are discriminatory against gay and bisexual men in that they amount to a de facto permanent exclusion on the grounds of sexual preference, and are unfair, as other groups with similar risks of HIV infection are allowed to donate blood after shorter time-period deferrals designed to cover the seroconversion window. On the opposite side of the discussion, recipient advocacy groups and regulators are understandably adverse to any change that is not centered on improving safety. Recipient groups argue that they have suffered greatly due to transmission of HIV and HCV by transfusion, and they will be the bearers of any increase in risk that may result from policy changes. Because both MSM and recipients are vulnerable groups that have suffered in the past, the debate over possible changes in criteria has ethical, societal, and emotional dimensions not seen in discussions concerning other donor selection criteria. Of particular concern to blood operators is the prospect that young eligible donors may be dissuaded from donating blood to institutions that are perceived to act in a discriminatory and unfair fashion. This International Forum seeks to describe approaches to this issue and challenges to the status quo, in a snapshot in time. Since it is extremely difficult to obtaindatatoevaluatethepossibleimpactofpolicy changes made to address concerns expressed by advocacy groups, comparison of international practice is particularly valuable, since we may learn from approaches implemented in other jurisdictions. We received responses from 24 respondents representing countries on six continents. In most, but not all, the MSMpolicy isdetermined atthe national level. The following questions were asked of the respondents

BACKGROUND: In Italy, the law does not permit the setting up of private banks to preserve cord blood (CB) stem cells for personal use. However, since 2007 the right to export and preserve them in private laboratories located outside Italy has existed, and an increasing number of women are requesting this collection of umbilical CB at delivery to enable storage of stem cells for autologous use. STUDY DESIGN AND METHODS: Since private banks recruit clients mainly via the Internet, we examined the content of 24 Italian-language websites that offer stem cells storage (from CB or amniotic fluid), to assess what information is available. RESULTS: We found that the majority of private banks give no clear information about the procedures of collection, processing, and banking of CB units and that the standards offered by private CB banks strongly differ in terms of exclusion or acceptance criteria from the public banks. These factors may well influence the overall quality of the CB units stored in private CB banks. Of note, during the period 2007 to 2009, the number collected for autologous use did not create a downward trend on the number of units stored in public CB banks for allogeneic use. CONCLUSION: CB is a valuable community resource but expectant parents should be better informed as to the quality variables necessary for its storage, both by institutions and by professionals. Currently, most of the advertising is insufficient to justify the expense and the hopes pinned on autologous use of CB stem cells.

BACKGROUND: Several researches on aging red blood cells (RBCs)—performed both in vivo and under blood bank conditions—revealed that RBC membrane proteins undergo a number of irreversible alterations, mainly due to oxidative stress. The individuation of proteins to be used as indicators of irreversible RBC injury and to be proposed as candidate biomarkers of oxidative damage or aging status during blood storage is therefore of great interest. STUDY DESIGN AND METHODS: Based on this purpose we performed proteomic analysis of the membranes of RBCs during various storage periods under blood bank conditions. Changes in protein composition of RBC membranes were monitored as a function of the storage period by means of polyacrylamide gel electrophoresis coupled with immunoblotting and mass spectrometry analyses. RESULTS: During storage, a progressive linkage of typical cytosolic proteins to the membrane was detected, including both antioxidant and metabolic enzymes (such as catalase, peroxiredoxin-2 [Prx2], and 2,3-bisphosphoglycerate-mutase), as well as nonreducible cross-linkings of probably oxidized or denatured hemoglobin. This phenomenon was unequivocally related to oxidative stress, since storage of RBCs under anaerobic conditions showed a suppression of these protein recruitments to the membrane. CONCLUSION: The detailed analysis of these protein associations to the membrane of aged RBCs allowed Prx2 to be suggested as a potential RBC oxidative stress marker for the sake of developing new approaches in quality assurance of blood components. D uring storage, red blood cells (RBCs) undergo a number of structural, metabolic, and functional modifications, 1 some of which are reversible while others are not. These changes include RBC shrinkage, membrane remodeling, slowed metabolism with decreased concentrations of adenosine triphosphate, acidosis with resulting decreased concentrations of 2,3-diphosphoglycerate acid (DPG), loss of intracellular potassium, hemolysis, oxidative injury with changes in Band 3 structure and lipid peroxidation, membrane loss, and vesiculation. 2,3 It is largely unknown how

Since the genomic era has not fully kept its promises, studies addressing the protein complement to the genome have been recently gaining momentum. Proteomics investigations could be potentially used from bench to bedside, in order to test the quality of collected blood components prior to or during storage. In parallel, proteomics could be used to verify the effects of the production and pathogen reduction processes of plasma derivatives and blood components on the protein fractions, or to reduce the effects of storage lesions. Another area of interest is represented by the discovery of peculiar biomarkers readily adoptable for targeted evaluation of blood-component integrity or functionality, as well as to assess the proliferative capacity of hematopoietic stem/progenitor cells. These accumulating basic research evidences will hopefully be accompanied by actual applications in routine clinical practice. Whether the costs of the needed facilities (instruments and trained personnel) will meet the current demand of the clinical market, proteomic-expert transfusionists will no longer only inform, but also perform a role in clinical routine.

Background and Objectives Two External Quality Assessment Programmes (EQAPs) were run in 2008 and 2009 to evaluate the proficiency of blood centres in detecting, by nucleic acid amplification techniques (NAT), the possible contamination of plasma with hepatitis C virus (HCV), human immunodeficiency virus (HIV) and hepatitis B virus (HBV). Materials and Methods In the EQAP-2008, three customized panels were designed; each containing positive samples with a viral nominal concentration for the three viruses of about three times the 95% DL of the respective commercial NAT assay. In the EQAP-2009, the proficiency of the participants was evaluated with a single panel, independently on the NAT method used. Results While 84% (102/122) of the participants in the EQAP-2008 correctly identified the positive and negative samples of the panels, in the EQAP-2009 the percentage of proficient laboratories increased to 97% (118/122). Most importantly, in this 2-year experience, we observed a decrease in the number of pre-/postanalytical errors, from 14 in 2008 to two in 2009. Conclusions The design of these two EQAPs allowed participants to assess the performance of the NAT methods applied in their routine screening of blood donations, not only with respect to analytical errors but also to human errors that, despite the high level of automation reached by NAT methods, can still occur.

Since the first successful haematopoietic stem cell transplantation (HSCT) using cord blood from a sibling in 1988 and the establishment of the first public umbilical cord blood bank in New York Blood Center in 1992, umbilical cord blood banks have been instituted in many countries. Funding was received from regular blood banks, health councils, charity funds or commercial investments. The international medical society is indebted to the New York Blood Center for publishing their procedures and EuroCord for fighting a patent on cord blood processing. Although it is unknown how many cord blood samples are currently banked and have been transplanted worldwide, the figures of the international registration of World Marrow Donor Association (WHDA) show an increase of cord blood use, in addition to other sources of unrelated HSCT (Fig. 1). Cord blood for HSCT is, in addition to national/regional use, exchanged worldwide. Donor counselling, human leucocyte antigen (HLA)-typing, tests for transmittable diseases and product quality control requirements to comply with (inter)national [AABB, Paul-Ehrlich-Institut, NetCord/ Foundation for the Accreditation of Cellular Therapy (FACT)] standards are expensive, making storage of cord blood for unrelated allogeneic haematopoietic transplantation currently a loss-making activity, not particularly attractive for private enterprise. In the last years, hopes have been fueled that other stem cells in cord blood may be used for future repair of metabolic or degenerative diseases. Autologous or personal cord blood banking appeals to individual initiatives and private funding; money is desperately needed by allogeneic cord blood banks, and it would be much better if it could

BACKGROUND: This study was aimed at obtaining significant information on the quality of whole-blood plasma (WBP) delivered to a private pharmaceutical company by the blood transfusion centers (BTCs) of 10 Italian regions. STUDY DESIGN AND METHODS: A statistical sampling plan of plasma units took into account the contribution each selected blood transfusion center, belonging to the 10 regions, made to the plasma pool annually delivered to the pharmaceutical company. A total of 1787 plasma units were selected for coagulation Factor VIII (FVIII:C) and Factor VIII antigen (FVIII:Ag) analysis. RESULTS: The FVIII:C mean value was 0.99 IU per mL; it was significantly lower in O units (0.86 IU/mL) than in non-O units (1.08 IU/mL). The mean value of FVIII:Ag was 0.90 IU per mL; it was significantly lower in O units (0.78 IU/mL) than in non-O units (0.99 IU/mL). In units with a FVIII:C level of less than 0.70 IU per mL, the FVIII:Ag mean value (0.62 IU/mL) was higher in comparison to the FVIII:C mean value (0.57 IU/mL). Instead, in the units with a FVIII:C level of at least 0.70 IU per mL, the mean level of FVIII:C (1.08 IU/mL) was higher than that of FVIII:Ag (0.96 IU/mL). CONCLUSIONS: The mean value of FVIII:C (0.99 IU/mL) in whole-blood plasma produced by the 10 Italian regions is higher than that reported in other studies. A total of 83.1 percent of units have a FVIII:C level of at least 0.70 IU per mL. The mean level of FVIII:Ag is lower than that of FVIII:C. FVIII:Ag is higher in those units with a FVIII:C level of less than 0.70 IU per mL, while it gradually decreases as FVIII:C exceeds 0.70 IU per mL, thus showing a greater resistance to handling of plasma in the production steps mostly affecting FVIII:C stability.

Anemia is one of the world’s most common disorders. In 2010, global anemia prevalence was 32.9%, affecting over 2.2 billion people, and iron deficiency the most common of the causes.[1][1] Oral iron, while inexpensive and effective when taken and tolerated, is frequently associated with unpleasant

Background and Objectives Despite the procedures adopted for the selection of blood donors, in Italy the HIV prevalence per 100 000 repeat tested donors (RTD) and first-time tested donors (FTD) is high compared to most other Council of Europe member states. To evaluate the effectiveness of predonation procedures, we studied both the characteristics and the undisclosed risk behaviours of HIV-positive donors. Materials and Methods We analysed the data from the Italian blood donor surveillance system in 2009, 2010 and 2011. Based on the postdonation interview, HIV-positive donors were classified by risk behaviour (heterosexual, MSM, ‘non-sexual’ and ‘not determined’) and by time elapsed from risk behaviour to donation. In Italy, the temporary deferral for exposure to behaviour at risk is 4 months. Results In the postdonation interview, 113 HIV-positive donors (32·4%), who denied at-risk behaviours in the predonation selection, reported sexual risk behaviours

Background In the countries with high G6PD deficiency prevalence, blood donors are not routinely screened for this genetic defect. G6PD deficiency is often asymptomatic, blood donors may be carriers of the deficiency without being aware of it. The aim of the study was to evaluate the prevalence of G6PD deficiency among the Italian blood donors. Design and Methods From October 2009 to April 2011, 3004 blood donors from a large hospital transfusion centre were screened for G6PD deficiency using differential pH-metry and the characterization of G6PD mutations was performed on G6PD-deficient subjects. The haematological features of G6PD-deficient and normal donors were also compared. Results Thirty-three subjects (25 men and 8 women) with low G6PD activity were identified, corresponding to 1·1% of the examined blood donor population. The frequencies of class II severe alleles (Mediterranean, Valladolid, Chatham and Cassano) and class III mild alleles (Seattle, A- and Neapolis) were 48% and 43%, respectively. The haematological parameters of G6PD- donors were within normal range; however, the comparison between normal and G6PD- class II donors showed significant differences. Conclusion In Italy, the presence of blood donors with G6PD deficiency is not a rare event and the class II severe variants are frequent. The identification of G6PD-deficient donors and the characterization of the molecular variants would prevent the use of G6PD-deficient RBC units when the haemolytic complications could be relevant especially for high risk patients as premature infants and neonates and patients with sickle cell disease submitted to multiple transfusions.

There have been great advances over the last decades in haematopoietic stem cell (HSC) transplantation, using either bone marrow, peripheral blood or cord blood-derived stem cells. The coming into force of the European legislation on tissues and cells and the consequent transposition of Directives into national laws have required the health authorities in the Member States (MS) and the scientific societies to review the transplantation activities to ensure the circulation of safe HSC products. Here, the regulatory inspection process performed by the Competent Authorities and the professional voluntary accreditation process of the Transplant Programmes active in Italy is compared.

H. W. Reesink, S. Panzer, C. A. Gonzalez, N. Lena, P. Muntaabski, S. Gimbatti, E. Wood, M. Lambermont, V. Deneys, D. Sondag, T. Alport, D. Towns, D. Devine, P. Turek, M.-K. Auvinen, T. Koski, C. K. Lin, C. K. Lee, W. C. Tsoi, E. Lawlor, G. Grazzini, V. Piccinini, L. Catalano, S. Pupella, H. Kato, S. Takamoto, H. Okazaki, I. Hamaguchi, J. C. Wiersum-Osselton, A. J. W. van Tilborgh, P. Y. Zijlker-Jansen, K. M. Mangundap, M. R. Schipperus, D. Dinesh, P. Flanagan, O. Flesland, C. T. Steinsvag, A. Espinosa, M. Letowska, A. Rosiek, J. Antoniewicz-Papis, E. Lachert, M. B. C. Koh, R. Alcantara, M. Corral Alonso & E. Muniz-Diaz

Abstract 4195 Directed family cord blood (DCB) storage provides hemopoietic stem cell source for transplantation (HSCT) for families with an existing or a potentially future recipient with HSCT curable disease (D). The National CB Banks Network in Italy (ITCBN) has a leading role in providing public DCB service for high-risk families, in compliance to GITMO directives for eligibility criteria (HSCT curable D: malignant MD, non MD, inherited ID). To provide best cost-effective practices recommendations it is important to report on DCB procedures and HSCT rate (HSCT-R) among public Banks. By 12.12.2008 almost 1800 DCB units were stored in 18 Italian Banks and 104 (9%) issued for HSCT. The present survey aims at summarizing the over 15 yrs DCB experience among 5 ITCBN Banks active since 1997 (range 1990-1997), and including 670 DCB units. Results Preliminary analysis reports a 94% overall compliance to eligibility criteria directives, and overall HSCT- R for an alive sibling of 12% (63/522); the 63 HSCT were 97% matched, for curing ID in 84% and with 72 % overall survival outcome. Different policies among Banks were compared (Bank vs others: 1) eligibility criteria distribution : Bank PV06 DCB for MD Conclusion. Advice for public long-term DCB storage should depend on HLA compatibility, potential recipient, disease progression, and likelihood/ timing of using DCB; Italian CB Banks are actively cohoperating to find best public banking practices to ensure a CDB storage system that is ethical, cost effective and responsive to patient needs. Disclosures: No relevant conflicts of interest to declare.