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Increased transplant activity calls for improved stem cell collection, especially when peripheral blood is the preferred source of haematopoietic progenitor cells (HPCs). Plerixafor is a bicyclam molecule that mobilizes CD34+ cells by reversibly disrupting CXCR4-CXCL12-supported HPC retention. Plerixafor is given with granulocyte colony-stimulating factor (G-CSF) to help harvest autologous CD34+ cells for transplantation when mobilization with G-CSF fails. Mobilization protocols with the same doses of plerixafor and G-CSF have been used off-label in healthy allogeneic donors, with equal success and scarce side effects, both in adult and paediatric patients. Plerixafor has also been used as a sole mobilization agent. Plerixafor alone or coupled with G-CSF might lead to harvesting distinct cellular populations conferring improved engraftment properties and increased survival. Those characteristics might make plerixafor an especially attractive mobilization agent, particularly for non-related donations. However, available data are limited, and long-term follow-up is needed to clarify the best scenario for using plerixafor with or without G-CSF in healthy donors. In this review, we will summarize the evidence supporting this practice, highlighting the practical aspects and providing clues for an expanded use of plerixafor.

Despite the effectiveness of plasma exchange (PEX) and immunosuppressants in the treatment of acquired thrombotic thrombocytopenic purpura (aTTP), a number of patients still die as a result of the disease. Whether caplacizumab could rescue these patients remains still unsettled. The objective of this study was to characterise mortality patterns and prognostic factors in the first episode of aTTP. We queried the Spanish TTP Registry for patients with a diagnosis of aTTP in their presenting episode who fulfilled complete clinical and follow-up data (n = 102). The patients were diagnosed between 2004 and 2018, and all were treated with daily PEX and corticosteroids. Clinical and laboratory data were analysed at diagnosis and during the treatment course. Eight patients (7.7%) died between 12 h and 36 days after presentation, and could be classified into three patterns: death before treatment, early death driven by acute cardiac or neurologic events, and late death due to unremitted aTTP. Stupor or coma at diagnosis and platelet count < 20 x 10(9) /L by the 6th treatment day were independently associated with increased risk of death. Stupor or coma at diagnosis and lack of response to PEX by the 6th day in patients experiencing the first episode of aTTP are strong predictors of mortality. These patients could be rescued by novel agents aimed at halting the microvascular thrombosis until adequate immunosuppression is achieved.

Chronic lymphocytic leukemia (CLL) is characterized by a failure in the mechanisms of apoptosis that leads to an accumulation of mature B cells in peripheral blood, bone marrow, and lymphoid organs. The molecular basis of CLL remains unknown. Certain cytogenetic and molecular markers determine a bad prognosis in CLL. Fanconi anemia complementation (FANC) proteins have been related to chromosomal instability and alterations in the mechanisms of p53 activation, control of cell cycle, and apoptosis. We investigated the role of certain FANC proteins in CLL. Our data identified a group of patients with CLL with high expression of FANCA in peripheral B-CLL cells and we established its relationship with the deletion of 11q23 and a worse prognosis. When we investigated the molecular mechanisms of this bad prognosis, we observed a reduction in the expression of 2 p53 target genes, p21 and ∆Np73, in CLL primary cells transfected with FANCA. Functional studies demonstrated an impairment of p53 by FANCA. Moreover, we obtained evidence of a cooperation between FANCA and the NEDD8-interacting protein NUB1L in the destabilization of p53. For the first time, FANCA is reported as a bad prognosis marker by a mechanism other than its role in the Fanconi anemia-breast cancer DNA repair pathway.-Bravo-Navas, S., Yanez, L., Romon, I., Pipaon, C. Elevated FANCA expression determines a worse prognosis in chronic lymphocytic leukemia and interferes with p53 function.

Background Older patients, frequently with multiple comorbidities, have a high mortality from COVID-19 infection. Convalescent plasma (CP) is a therapeutic option for these patients. Our objective is to retrospectively evaluate the efficacy and adverse events of CP treatment in this population group. Methods Forty one patients over 80 years old with COVID-19 pneumonia received CP added to standard treatment, 51.2% with high anti-SARS-CoV-2 IgG titers and 48.8% with low titers. Median time between the onset of symptoms and the infusion of plasma was 7 days (IQR 4–10). A similar group of 82 patients who received only standard treatment, during a period in which CP was not available, were selected as a control group. Results In-hospital mortality was 26.8% for controls and 14.6% for CP patients (P = 0.131) and ICU admission was 8.5% for controls and 4.9% for CP patients (P = 0.467). Mortality tended to be lower in the high-titer group (9.5%) than in the low-titer group (20%), and in patients transfused within the first 7 days of symptom onset (10%) than in patients transfused later (19.1%), although the differences were not statistically significant (P = 0.307 and P = 0.355 respectively). There was no difference in the length of hospitalization. No significant adverse events were associated with CP treatment. Conclusions Convalescent plasma treatment in patients over 80 years old with COVID-19 pneumonia was well tolerated but did not present a statistically significant difference in hospital mortality, ICU admission, or length of hospitalization. The results should be interpreted with caution as only half the patients received high-titer CP and the small number of patients included in the study limits the statistical power to detect significant differences. Trial registration CEIm Cantabria # 2020.127.

Introduction Temperature and time conditions during storage and distribution of blood components (BC) and their permissible deviations are strictly regulated. The degree of compliance with these requirements in daily practice of transfusion services (TS) is not well known. Materials and methods We conducted a survey among Spanish hospital TS covering different aspects of BC management in their daily activity. Results Eighty-three TS managing 56 % of total transfusions answered the survey. Monitoring of red blood concentrates (RBC) temperature during in-hospital distribution was routinely performed by only 12 % of the TS. The main criterion for BC re-entry into the stock was the total time spent outside controlled temperature. Up to 41 % of the TS apply the “30-minute rule” to distributed RBC, while most services use a 60-minute rule for PC. No adverse events were detected when RBC that had remained longer than 30 or 60 min outside the TS were transfused. Fresh frozen plasma is usually thawed 2 h preissue and stored at 4 °C up to 24 h. Discussion and conclusions In the Spanish context, the 30- and 60-minute rules for re-entry of RBC and PC into the TS stock are loosely followed. Feedback for a large number of TS suggests that the extension of the 30-minute RBC rule to at least 60 min is feasible, if other safety requirements are met. Flexibility with some requirements could help reduce product loss without deleterious effect on BC safety.

Resumen Objetivo Analizar y mejorar el proceso de atencion a la hemorragia posparto mediante simulacion y analisis del factor humano (interaccion de los profesionales en el sistema donde trabajan). Metodos El proyecto se realizo entre junio de 2016 y mayo de 2017. El grupo de trabajo se creo segun el metodo de liderazgo participativo incluyendo profesionales con conocimiento y cargo para influir en la organizacion. Se revisaron el proceso y los protocolos clinicos existentes. Se empleo la simulacion clinica para la observacion directa en el hospital y se analizo su rendimiento. Se amplio la informacion obtenida mediante entrevista abierta y estructurada a profesionales seleccionados por su experiencia en el tema a estudio. Se utilizo un analisis de tareas para documentar el proceso, y un analisis de modo de fallos y efectos para evaluar vulnerabilidades del sistema. Los resultados se representaron mediante un flujograma. Resultados El analisis identifico seis grupos de personas trabajando en tareas diferentes, su secuencia de actuacion, la importancia de explicitar un coordinador, el modo en que se propaga y transforma la informacion, y los puntos donde es necesario tomar decisiones clave y compartir la informacion. Se integraron los protocolos existentes y ayudas para utilizar los recursos disponibles, como la extraccion de analiticas y la administracion de hemostaticos. Conclusiones El analisis del proceso de asistencia a una paciente con hemorragia posparto utilizando la simulacion clinica, junto con el analisis del factor humano, que estudia la interaccion de los profesionales entre si y con el sistema donde trabajan, permitieron establecer un mapa detallado y personalizado de los componentes que determinan como el trabajo fluye a traves de la organizacion.

Introduction Therapeutic plasma exchange (TPE) is the first-line treatment for acute thrombotic thrombocytopenic purpura (TTP). Methylene blue-plasma (MBP) has been used for over 20 years, but its efficacy in this setting remains controversial. Patients and methods: this is a comparative analysis of the experience of two Centres, with different plasma products, to evaluate their efficacy in TTP. One centre used quarantine plasma (QP), and MBP the other. We performed a retrospective longitudinal study, analysing the clinical files of TTP patients of a 13-year data evaluation period. Duration of treatment and transfusion parameters, medical record, laboratory testing, concomitant medication, and survival rate, were assessed for every episode. Results During the study period, 12 (55.5 %) and 10 (45.5 %) new cases were treated with QP and MBP, respectively. There were no significant differences between the mean numbers of TPE processes, days elapsed from diagnosis to TPE, and plasma volume transfused. The QP TPE episodes of treatment were significantly associated with an increased time to recovery compared with MBP episodes of treatment (p = 0.004). Conclusion MBP was as effective as QP in the treatment of TTP patients. Since recovery was more favourable when MBP was used, we consider MBP remains a suitable alternative to treat TTP patients.

Background removal of incompatible red blood cells (RBCs) or plasma is usually required to avoid hemolysis during infusion of ABO incompatible bone marrow (BM) allogeneic transplants. This process often involves separation of buffy coat (BC) by centrifugation in automated devices. We have evaluated the Spectra Optia™ (Optia) apheresis system to determine its effectiveness in BC concentration, volume reduction and RBCs depletion of ABO-incompatible BM compared with our previous method using Cobe Spectra™ (Cobe). Materials and methods 28 processes were performed with Optia and 52 with Cobe. We compared volume reduction, RBCs depletion, and recovery of total nucleated cells (TNCs), mononuclear cells (MNCs), CD34+ and CD3+ cells in the final product. Hematopoietic engraftment was ascertained. We used Saphiro-Wilks and Kolmorgorov- Smirnov tests to test normality and Mann-Whitney’s U test to compare means between both groups. Results We found statistically significant differences favoring Optia versus Cobe in TNCs recovery (62% vs. 37%), CD34+ cell recovery (98 vs 84%), volume reduction (91 vs 84%), and RBCs depletion (99 vs. 97%), but not in processing time or time to engraftment. Conclusion Optia achieves high RBCs and volume depletion of BM, while providing excellent CD34+ recovery in clinical routine. Some parameters compare favorably with Cobe Spectra.

To analyse and redesign the care process for patients with severe post-partum haemorrhage using simulation and a human factors approach.The project was developed between June 2016 and May 2017. The working group was created following the participatory leadership method and included professionals with knowledge and position to influence the organisation. The existing process and clinical protocols were reviewed. An in situ simulation was used to observe team performance in the hospital recovery room. Information was expanded through an open and structured interview with professionals selected for their experience in the subject matter. Task analysis was used to document the process, and a failure mode and effects analysis was made to assess system vulnerabilities. Results were mapped using a flow chart.The analysis identified six groups of people working on different tasks, their activities and sequence of action, the importance of naming an explicit coordinator, the way in which information is disseminated and transformed, and the stages where it is necessary to share information and make key clinical decisions. The existing clinical protocols and the aids established in order to use the available resources were integrated, including blood draws and haemostatic agents, as well as an administration guide.The analysis of the patient care process in post-partum haemorrhage using in situ simulation with a human factors perspective, including an analysis of the interaction between professionals and the system where they work, established a detailed and personalised map of the components that determine how work flows through the organisation.

Background: Current guidelines recommend the use of antifungal prophylaxis during, at least, the first three months post allogeneic stem cell transplantation (allo-SCT). However, these drugs are not exempt of adverse effects due to their own toxicity or drug-drug interactions. In addition, breakthrough mold infections seem to be emerging as a new problem in this setting. Objectives: The aim of this study was to analyze the benefit of a strategy in which allo-SCT patients were not routinely prescribed antifungal drugs except for the case of the development of neutropenic fever and/or exposure to high dose of corticosteroids. Main objectives were 1) requirement and time of exposure to antifungal treatment and 2) cumulative incidence (CI) of proven or probable IFI at 1, 3 and 6 months after transplant. Other objectives were IFI description and overall survival (OS). Patients and methods: 319 patients who underwent a first allo-SCT at our center between 2010 and 2017 and were not under antifungal prophylaxis at the moment of transplant were included. 181 patients (57%) were males and median age was 51 years, range (4-74). Acute myeloid leukemia (35%) was the most frequent diagnosis and myeloablative conditioning regimen was mostly used (69%). 99 patients (31%) received the stem cells from a mismatched donor and BM was the preferred stem cell source (72%). Fourteen patients (4%) did not engraft. The median length of neutropenia Results:Thirty-one 31 patients (9.7%) did not receive antifungal drugs along the course of the transplantation, 58 patients (18%) required it for less than 1 week and only 24% were on therapy more than 3 weeks. The median total days on antifungal drugs was 13 days (0-175) for the entire population and 11 days (0-109) in patients who did not develop fungal infection and/or acute GVHD II-IV. Fluconazole (61%) was the main antifungal drug used during the neutropenic phase, followed by caspofungin (27%). Time on fluconazole was significantly shorter than caspofungin, 8 vs. 11 days, p=0.001. A change on antifungal therapy was needed in 130 (45%) patients and was more frequent in those who were receiving fluconazole (57%) compared to those who were receiving caspofungin (20%), p The CI of proven or probable IFI at day 30, 90 and 180 after transplant was 2.5%, 5.1% and 5.5%, respectively. Very importantly, none of the 106 patients who did not receive antifungal drugs or received less than one-week developed IFI. Twelve mold infection, 4 in the postmortem study, and 5 yeast infection were diagnosed. Microbiological identification was obtained in 9 patients; C. parapsilosis (3), Rhizopus (2), C. orthopsilosis (1), Criptococo laurentii (1), A. fumigatus (1), Alternaria spp. (1). The restricted administration of antifungal drugs did not affect the overall survival, Figure 1. Conclusion: In our experience, a restrictive strategy for the use of antifungal drugs in the setting of allo-SCT is feasible and effective. It results in similar cumulative incidences of fungal infection than the recommended policy. Moreover, it allows almost 10% of patients to remain free of antifungal treatment throughout the procedure and one fourth of them being exposed for less than a week. This data supports the change in the antifungal prophylactic paradigm for allo-SCT patients. Figure 1 Disclosures No relevant conflicts of interest to declare.

Background Patients undergoing hematopoietic stem cell transplantation (HSCT) are at high risk of multiple complications being graft versus host disease (GvHD) one of the most concerning. Addition of anti-T-lymphocyte globulin (ATG-Fresenius ®) reduces the incidence of acute and chronic GvHD however, optimal dose has not yet been established. Standard dose (60 mg/kg) has shown a significantly lower moderate-severe cGvHD yet its effect in Progression Free Survival (PFS) and Overall Survival (OS) is contradictory. Our primary objective was to analyze the efficacy of low ATG dose (21 mg/kg) in the prophylaxis of acute and chronic GvHD. As secondary objective we analyzed non-relapse mortality (NRM), infectious and non-infectious complications, GvHD and relapse free survival (GRFS), overall survival and progression free survival in high risk patients undergoing HSCT. Patients and methods We retrospectively analyzed 57 patients who underwent HSCT in our center from 2012 to 2017, receiving a total dose of 21 mg/kg (7 mg/kg on day -3, -2 and -1) of ATG as part of the GvHD prophylaxis, associated to cyclosporine/tacrolimus and MMF/short course-MTX. The conditioning regimen were myeloablative in 42 patients (73.7%). The donor was unrelated in 46 cases (80.7%). Seventeen (29.9%) had a mismatch (16 unrelated, 1 sibling). Stem cell source was peripheral blood in 51 patients (89.4%). Forty six (80.7%) patients were positive for CMV, from these 17 (36.9%) were paired with seronegative donors. The median age was 57 years old (18-70), 38(66.7%) were males. The most frequent diagnosis were Acute Myeloblastic Leukemia (40.4%), myelofibrosis (17.5%) and myelodisplastic syndrome (14%); 28 (49%) had a HCTI score ≥ 3 and 16 (29%) a high risk DRI score. Thirty patients (52.6%) were in complete remission at the moment of HSCT. (Table 1) Results Hematopoietic engraftment was observed in 54 patients (94.7%). The median neutrophil and platelet engraftment were 14 (10-34) and 15 (9-28) days, respectively. Primary graft failure occurred in 3 patients (2 myelofibrosis, 1 AML). Twenty (39.2%) out of 51 evaluable patients developed grade 2-4 acute GvHD. The cumulative incidence of grade 3-4 aGvHD was 8.8% (95% CI, 3.2-17.9%). Skin was the most affected organ (62%). We found a cumulative incidence of moderate to severe cGvHD of 35.2% (95% CI 22.7-47.9%), only 5 cases (10.6%) were severe, with a median onset at day 177 (57-893). The median duration of immunosuppresive systemic therapy was 488 days (207-2046) in the group of patients with moderate to severe cGvHD. Twelve patients died due to transplant related events, 7 were reported before day 100, all of infectious etiology. The NRM at two years was 21.9% (95% CI, 12-33.7%). Eleven patients (19.2%) had at least two episodes of CMV reactivation and one had cytomegalic gastrointestinal disease. One patient developed postransplantation lymphoproliferative disorder associated to Epstein Barr virus. Twenty patients (35%) developed noninfectious complications, being hemorrhagic diathesis, hepatotoxicity and severe mucositis the most frequents. With a median follow up of 28 months in alive patients (3-67), the GRFS at one year, OS and PFS at two years were 47.6% (95% CI, 42.8-52.2%), 59% (95% CI, 54.5-63.2%) and 52% (95% CI, 46.9-56.5%), respectively. The relapse incidence at two years was 26.3% (95% CI 14.7-39.4%). Conclusions In our center, the use of low ATG doses is protective against severe forms of acute GvHD, offering also a moderate protection against chronic GvHD in a cohort with high prevalence of mismatched unrelated donors, high median age and high risk DRI and HCTI. This approach doesn't seem to have a significant negative impact neither in GRFS, OS and PFS at two years. Disclosures No relevant conflicts of interest to declare.

Background: Chronic lymphocytic leukemia (CLL) is the most common hematological malignancy in western countries. It is characterized by a failure in the mechanisms of apoptosis that leads to an accumulation of mature B cells in peripheral blood, bone marrow and lymphoid organs. With exceptions, CLL is considered incurable and some patients show a worse prognosis related to the expression of certain cytogenetic or molecular markers such as p53 dysfunction (17p13 deletion or TP53 inactivation), 11q23 deletion, unmutated IgVH and the presence of a complex karyotype. FANC proteins have been related to chromosomal instability and alterations in the mechanisms of p53 activation, control of cell cycle and apoptosis. Germline mutations in any of the 20 FANC genes known so far generates Fanconi Anemia, a syndrome characterized by a extraordinary proneness to cell apoptosis leading to a progressive bone marrow aplasia and pancytopenia. Some FANCA proteins aggregate in response to DNA damage forming the FANCcore complex that mediates the monoubiquitination of FANCD2 and FANCI, thus activating the mechanism to repair stalled replication forks. In addition, individual FANC proteins have been involved in functions out of the FANCcore. This is the case of FANCA, that has recently been involved in the neddylation of CXCR5 and beta-2-microglobulin, processes reported to be altered in CLL. Hypothesis: Given the fragmentary information connecting FANC proteins with cellular processes altered in CLL, like apoptosis, cell cycle or neddylation, we hypothesize a role of these proteins in the diagnosis or prognosis of CLL. Methods: We analyzed the expression of 5 FANC genes in a cohort of 160 patients of CLL by quantitative RT-PCR. Statistical analysis were carried out to establish relations between FANC genes deregulation and clinical manifestations. We also investigated the role of the FANCA gene in primary circulating B-lymphocytes from CLL patients by either gain- or loss-of-function approaches. Results: Our data identified a group of CLL patients with high expression of FANCA in peripheral B-CLL cells, and we stablished its relationship with the deletion of 11q23 and a worse prognosis. When we investigated the molecular mechanisms of this bad prognosis, we observed a reduction in the mRNA expression of two p53 target genes, p21 and ∆Np73, in CLL primary cells transfected with FANCA. Luciferase studies demonstrated an impairment of p53 function by FANCA. Moreover, we obtained evidence of a cooperation between FANCA and the NEDD8-interacting protein NUB1L in the destabilization of p53. Conclusion: These results point to FANCA as a bad prognosis marker in CLL and unveils a new role of this protein aside from its role in the FA-BRCA DNA repair pathway. Disclosures No relevant conflicts of interest to declare.

BACKGROUND AND OBJECTIVES. Post transplantation High dose Cyclophosphamide (PTCY) used in haploidentical hematopoietic transplantations, has a high effectivity in acute Graft versus Host Disease (aGVHD), and chronic Graft versus Host Disease prophylaxis (cGVHD), however it is associated with high relapse rates. On the other hand, Anti-T-Lymphocyte Globulin (ATG-Fresenius ®) is also effective as immunosuppressive (IS) drug, but its benefit on Overall Survival (OS) and Relapse Free Survival (RFS) is unclear. The aim of this study was to compare the effectiveness of two GVHD prophylaxis regimes used in high risk transplantation: PTCY used in Haploidentical transplantation and ATG used for peripheral blood, non-related, related and mismatched donors. The primary endpoint was to evaluate the incidence of aGVHD and cGVHD, and its severity in both groups. As secondary endpoints we analyse the OS, RFS and GRFS (recorded adverse events include grade 3-4 aGVHD, systemic therapy-requiring cGVHD, relapse or death during median follow-up). We also consider transplantation related mortality (TRM) and post-transplantation complications. PATIENTS AND METHODS. We retrospectively analyse 111 allo-transplantations performed at our institution between 2012 and 2017. We analyse two cohorts: 49 haploidentical transplantation with PTCY (50 mg/kg, on day +3, +4) followed by Tacrolimus and Mycophenolate; and 62 peripheral blood related, non-related and mismatched with low dose ATG Fresenius (7mgr/Kg on days -3, -2, -1) associated with Tacrolimus/Cyclosporine starting on day -1 with a short course Methotrexate (on day +1, +3, +6) or Mycophenolate. Mycophenolate was stopped on day +28 and Cyclosporine or Tacrolimus were tapered on day +50. RESULTS. There were no differences in patients' age (49 vs 51), sex or pre-transplantation HCTI-score ≥ 3 (30 vs 26) between PTCY and ATG groups. We found differences between diagnosis (lymphoproliferative disorders (16 vs 4, p= 0.003), high DRI-score (18 vs 11, p = 0.04), number of previous transplantations (12 vs 5, p= 0.02), reduced intensity conditioning regimen (36 vs 20, p < 0.001) and bone marrow as stem cells source (38 vs 9, p < 0.001) between PTCY and ATG groups. The median time to neutrophil engraftment (>500/uL) was similar: 17 days [13-34] for PTCY and 16 days [9-33] for ATG. Median time to platelet recovery was higher in PTCY cohort (33 vs 18 days, p= 0.016). There were 3 secondary graft failures in PTCY group vs 4 graft failures in ATG (3 primary, 1 secondary). The were no differences in grade 2 - 4 aGVHD incidence between groups (PTCY:30.6% vs ATG:36.4%), but we found differences in grades 3 - 4 aGVHD (PTCY:4.1% vs ATG: 9%, p=ns). The global incidence of any NIH grade cGVHD was 56.1% in PTCY vs 66% in ATG group. Mild, moderate and severe cGVHD incidence were 31.7%, 19.5% and 4.8% for PTCY vs 28%, 26% and 12% in ATG (p=ns). The median duration of IS in alive patients with cGVHD was 6.5 months [3-19] in PTCY patients and 10 [3-34] in ATG group. Among moderate and severe forms, the median IS duration was 10 and 5 months in PTCY group vs 13 and 12 months in ATG respectively. PTCY cohort developed more non-infectious complications, especially, cardiac, lung, digestive and neurologic complications, (p=0.086), however there were not differences in infectious complications (Table 1). TRM was similar between groups, 18.4% for PTCY vs 22.5% for ATG, (p=0.250). We didn´t find differences in early toxic mortality ( With a median follow-up of 27 months in alive patients (28 months for PTCY and 22 months for ATG) we report an 67.8 % and 61% OS at 12 and 24 months for PTCY and 68.8% and 59.9% for ATG (Log Rank=0.971). Relapse free survival at 12 and 24 months was 61% and 57.9% for PTCY and 69% and 54% for ATG (Log Rank=0.839). GRFS at 12 and 24 months was 46.5% and 42.9% for PTCY patients and 40.7% and 33% for ATG patients, (Log Rank = 0.433). CONCLUSIONS. Regardless the different scenarios between transplantation cohorts, the use of PTCY and low dose ATG are equally effective in the prophylaxis of severe forms of aGVHD and cGVHD, offering similar GRFS. PTCY shows higher early toxicity but a similar rate of infectious events. In order to validate these results, it would be necessary to carry out a randomized controlled trial. Disclosures No relevant conflicts of interest to declare.

Transfusion services in the European Union must implement quality management systems to improve quality. Quality indicators (QI) play a key role in quality management because they can supply important information about the performance of the transfusion service, which can then be used for benchmarking. However, little is known about the actual use of QI in hospitals. We tried to ascertain the use and characteristics of QI in Spanish hospital transfusion services.We performed a survey among transfusion services in order to learn which QI they use. We classified indicators into categories and concepts, according to the steps of the transfusion process or the activities the indicators referred to.Seventy-six hospitals (17.9% of the hospitals actively transfusing in the country) reported 731 QI. Twenty-two of them (29%) were tertiary level hospitals. The number of indicators per hospital and by activity varied greatly. QI were assigned to some basic categories: transfusion process (23% of indicators), transfusion activity and stock management (22%), haemovigilance (20%), stem cell transplantation (9%), transfusion laboratory (9%), quality management system (8%), blood donation (3.4%), apheresis and therapeutic activities (2.5%) and immunohaematology of pregnancy (2%).Although most hospitals use QI in their quality management system and share a core group of indicators, we found a great dispersion in the number and characteristics of the indicators used. The use of a commonly agreed set of QI could be an aid to benchmarking among hospitals and to improving the transfusion process.

Transfusion-related acute lung injury (TRALI) can be a life-threatening complication of transfusion and it is probably underdiagnosed. Human leucocyte antigen (HLA) and granulocyte antibodies are thought to play a major role, but preventive measures are difficult to implement. In our regional blood centre, we implemented a preventive strategy avoiding donor deferral. Previously, pregnant apheresis donors were screened for HLA antibodies, and those with positive results were assigned to a plasma-only protocol. Plasma from these donors and from all previously pregnant whole blood donors was diverted for protein fractionation. Plasma-poor red blood cells (in additive solution, buffy coat removed) and platelets (pools with additive solution) were prepared. Prestorage leucodepletion was also applied. We found HLA antibodies in 18.1% of previously pregnant apheresis donors, and our strategy caused a 6.0% loss of apheresis platelets, a 4.8% increase of apheresis fresh frozen plasma (FFP) and a 7.8% loss of transfusable apheresis FFP. The effect on FFP from whole blood donors could be compensated. The platelet preparation method reduced the mean volume of plasma from each donor to 24.4 mL. Fifteen months after the start of our strategy, no cases of TRALI have been reported. Our experience shows that a practical strategy to prevent TRALI is feasible.

The Spanish Apheresis Group is a scientific association of physicians and nurses representing most of the medical centers in the country that are involved in apheresis. The group developed a survey in order to get information about the types and number of apheresis procedures performed in Spain. We received responses from 66 centers and we were able to collect data from at least one center of each autonomous region. There were 7 centers (11%) that did not perform any kind of apheresis procedures, 26 (39%) centers performed therapeutic apheresis procedures only, 18 (27%) centers performed apheresis donations only, and 15 (23%) centers performed both types of apheresis procedures. Regarding therapeutic apheresis in adult patients, plasma exchange (34%) and stem cell collections (30%) were the two therapeutic procedures most frequently reported, followed by erythrocytapheresis (13%) and extracorporeal photochemotherapy (11%). Regarding apheresis donation, our survey showed that the most frequent was multicomponent donation (45%) followed by plasmapheresis (28%) and single plateletapheresis (21%). When analyzing the current instrumentation for performing apheresis procedures, centers used the Spectra, Optia, and Trima devices (TerumoBCT) as the most frequent ones, followed by the MCS + (Haemonetics), Amicus (Fenwal), and Fresenius devices. In conclusion, we report here the first nationwide survey performed in Spain in order to get information about apheresis activities in our country. The survey is representative of Spain because we were able to collect data from at least one center from each of the different 17 autonomous regions, and we found a wide variety of therapeutic and donation procedures, as well as instrumentation used.

Introduction: Due to its production and mechanism of action, antithymocyte globulin (ATG) is associated with two main side effects: immunological responses and infections. Objective: We evaluate the incidence and differences of ATG infusion reactions and fungal and viral infections in patients who receive SCT across a period of 10 years. Patients and methods: From January 2005 to December 2014, 100 patients who underwent and allogeneic stem cell transplantation (SCT) in our center received ATG (Thymoglobulin [TG] or ATG-Fresenius [ATG-F]) as part of conditioning regimen. Because an out of trend had been noted in stability profiling of TG finished product lots manufactured since December 2009 and since July 2012, TG was switched by ATG-F, patients were divided into three groups (TG-1: 45 patients; TG-2: 31 patients; ATG-F: 24 patients). Total median dose of TG was 7.5 mg/Kg in both groups. Results: Patients transplanted with ATG-F were significantly older than those who received TG (p=0.009). In addition, the use of an unrelated donor and GVHD prophylaxis with calcineurin inhibitor combined with mycophenolate mofetil was more frequent in ATG-F group (p=0.04 and p Fungal infection was more frequent in TG-1 (30.2% vs 13.3% and 4.3%,p=0.024). CMV reactivation and BK viruria was more frequent in ATG-F (p=0.048 and 0.005, respectively). In contrast, EBV reactivation and Post Transplant Lymphoproliferative Disorder (PTLD) was more frequent in TG-2 group (33.3% vs 2.6% and 16.7%, p=0.003 and 25.8% vs 0% and 4.2%, p Conclusion During ATG infusion, pyrexia and chills are the most common side in SCT. The screening and prophylaxis of fungal infections may be associated with the diminishing of the incidence of this complication during the studied period. The use of older patients and the mycophenolate may be associated with an increasing incidence of CMV reactivation. By contrast, it is unclear if the out of trend noted in stability profiling of TG finished product lots manufactured since December 2009 has had influence in the type of infusion reactions and the incidence of EBV reactivations and PTLD observed in the TG-2 group. Disclosures No relevant conflicts of interest to declare.

Abstract 4408 Chronic transfusion dependence increases the risk of developing iron overload which potentially could have a negative impact on the patient. It has not yet been studied in depth the profile of chronic transfusion-dependent patients, and their therapeutic management. Our objective was to describe the clinical characteristics of chronic transfusion-dependent patients in Spain. An epidemiologic, cross-sectional and multicenter study was performed in 41 Haematology Services according to clinical practice. Patients ≥18 years old, who started to be chronically transfused after January 2007 and who had received at least 10 red blood cell (RBC) units at the time of inclusion were enrolled in the study. A total of 631 patients were analyzed, 56.2% were men with mean age of 65.0 years (deviation standard=17.0). The principal cause of transfusion dependence was of haematological nature (92.9%), being myelodysplasic syndromes (35.8%) the most frequent cause, followed by acute myeloid leukaemia (28.8%), medullary aplasia (6.3%) and myeloproliferative syndromes (6.0%). 15.5% of patients with non-haematological causes of transfusion dependence was observed, being neoplasia the most frequent cause (6.7%). A median of 22 RBC units were transfused in total to the population in study and a median of 14 RBC units were transfused in the last year. 59.3% of patients received ≥20 RBC units. Regarding iron overload, median serum ferritin (SF) level was 1,173.5 ng/ml and 48.7% of patients had SF ≥1000 ng/ml. SF level was not available in 16.3% of patients. Moreover, 18.7% of patients had their last SF measurement done before the study initiation while 64.8% of the SF measurements were performed during the study. The concomitant diseases reported were mainly cardiovascular (24.4%), urogenital (11.7%) and endocrine (10.1%). A higher number of comorbidities was observed in the group of patients with SF ≥1000ng/ml, specially cardiovascular, hepatic and endocrine disease. Of all patients with chronic transfusion dependence, 14.1% received chelation therapy, being deferasirox the most commonly used drug (89.0%). The reason for not receiving chelation treatment was unknown in 28.2% of patients. 13.2% of patients with iron overload did not receive chelation therapy due to present concomitant diseases: neoplasias (6.7%) and renal and urinary disorders (3.0%). A good correlation between transfused RBC units and SF levels was observed in the study (59.3% received ≥20 RBC units, and 48.7% had SF levels ≥1000ng/ml). It was noted that monitoring of iron overload by SF levels is not followed properly in patients with chronic transfusion dependence. 16.3% of patients did not have any SF measurement and in 18.7% of patients the last SF determination was prior to the study. These data may be related to the fact that 28.2% of patients did not receive chelation therapy due to unknown causes. Disclosures: No relevant conflicts of interest to declare.