bluuebunny/crossref_metadata_2025_split huggingface dataset:
PF779 VIABILITY OF HEMATOPOETIC STEM CELLS FOLLOWING STORAGE AT −80OC WITH 5% DIMETHYLSULFOXIDE AND HEMATOLOGIC RECOVERY IN TRANSPLANTED MYELOMA PATIENTS
Authors: Tonev I. , Simeonov S. , Mitkov I. , Ilieva M. , Petrov Y. , Ganeva P. , Arnaudov G. , Spassov B. , Mincheff M. 
Published: June 2019

Background:Dimethylsulfoxide (DMSO) is a major intracellular cryoprotectant, used for cryopreservation of stem cells. It is toxic to both cells and patients at temperatures above 0oC. Reduction of this effect is achieved by either washing of cells after thawing or by reduction of DMSO during freezing and storage. The latter requires addition of extracellular cryoprotectants to the freezing media.Aims:We assessed the effect of low DMSO concentration and different hematocrits of the frozen cells on cell viability and hematologic recovery in patients, transplanted for multiple myeloma.Methods:Cells were non‐programmed frozen and stored at −80oC in a cryoprotectant solution achieving final concentrations of 5% DMSO, 3.6% of hydroxyethyl starch (HES, Weight average molecular weight 450 000 Da) and 3% of human serum albumin. The cell concentration in the frozen product for the first 77 patients (84 transplantations) varied between 100x106 and 250x106 cells/ml. In an attempt to reduce the amount of DMSO infused, for the rest of the patients (n = 172; 192 transplantations) we further decreased the volume of the freezing suspension by removal of the entire plasma.The average age of the transplanted patients was 55 (35 ‐ 71). The cells were bedside thawed at 37oC water bath. The average cell dose was 2,95x106/kg (1,3 – 9,2x106/kg).Results:Viability of the stem cells following thawing assessed by trypan blue exclusion was 95,34% (70–99). The hematocrit of the frozen cells had no effect on cell viability (94,80%(low) vs 95,52%(high)). The major complaints, if any, during stem cell infusion were coughing and an increase in nausea and vomiting induced by the prior conditioning.The average time for hematological recovery was 11,66 days (between 9 and 19) for the neutrophils, and 12,17 (between 9 and 20) days for the platelets. There was no significant difference in viability and hematologic recovery (11,86 and 12,60 vs 11,59 and 12,02) between patients receiving cells frozen with low or high hematocrit.Summary/Conclusion:Dimethylsulfoxide, despite its cryoprotective properties, is toxic for stem cells at temperatures above zero C and induces many side effects (cardiac, neurologic, respiratory, etc.) in the patients. To reduce those side effects we use lower DMSO concentration, high hematocrit resulting in lower volume of the frozen cell suspension, thus reducing the final quantity of DMSO to be infused to the patients. This does not affect the cell viability or the hematologic recovery of patients after transplantation. Our easily performed method for unprogrammed freezing of stem cells with final DMSO concentration 5% at −80oC is safe, well tolerated, and provides cryopreservation, which allows high viability and stable cell engraftment, while reducing the undesired side effects of DMSO.
PF789 8‐YEARS’ OVERALL AND EVENT FREE SURVIVAL IS SUBOPTIMAL IN A LARGE GROUP OF TRANSFUSION‐DEPENDENT THALASSEMIC PATIENTS
Authors: Kattamis A. , Mikelatou A. , Koumasi K. , Nitsa E. , Rigatou E. , Kyriakopoulou D. 
Published: June 2019

Background:Current therapeutic modalities with proper transfusion regimen and chelation therapy have dramatically increased life expectancy and decreased anemia and iron overload related complications in transfusion dependent thalassemic (TDT) patients. In many countries where thalassemia prevention programs were introduced, the majority of TDT population is of middle age. Data on morbidity and new complications on this ageing thalassemics are sparse.Aims:To determine the 8‐years’ overall survival (OS) and event‐free survival (EFS) and to examine factors affecting survival in a large group of TDT patients.Methods:This is a retrospective analysis of mortality and morbidity in a large group of homogenously –treated TDT patients in a single institution. Patients with TDT, regularly transfused in our unit on 31/12/2010, were followed for 8 years till 31/12/2018. ‘New event’ was defined as a new complication significant enough to require therapeutic intervention. The effect of different factors (like age, splenectomy, history of hepatitis C, burden of transfusions, iron overload, etc) on mortality and morbidity was evaluated. Burden of transfusion was evaluated as continuous (cc of transfused red blood cells/kg/year) and dichotomous variable (up to, and, more than 10 units/12 weeks). The majority of adult TDT patients (76.4%) received >10 units/12 weeks.Results:435 patients (mean 33.3 ± 7.9 years, max 52.3 years) were longitudinally followed. During an observation period of 8 years, 30 deaths occurred, corresponding to an 8‐years OS of 93.1%. Deaths significantly increased after the age of 40 years (figure). Splenectomy and history of hepatitis C were risk factors for death (O.R. 7.0 and 4.5, respectively, both p < 0.05). Improvement of iron overload was noted between 2010 and 2018 (ferritin levels: 2108.6 ± 2098 vs. 1550.8 ± 1883.5 μg/l, respectively, p < 0.05). During the observation period, percentages of patients experiencing new events were as follows: hypothyroidism 20.7%, cardiac complications 8.6%, glucose homeostasis disturbances 7.3%, hypogonadism 21.6%, significant osteoporosis 6.4%, renal failure 1%, neurological complications 5.5% and cancer 6.1%. 8 years’ EFS was 55%. Apart from age, no other factors were related to the occurrence of new events.Summary/Conclusion:Despite adequate transfusion regimen and improvement on iron overload, OS and EFS of TDT patients remain suboptimal, with mortality increasing significantly after the 4th decade of life. Contributing factors to death, like splenectomy and history of hepatitis C, may be related to the initial treatment period. Effect of transfusion burden needs further evaluation. Ageing TDT population is likely to develop more complications with advanced age with the occurrence of malignancies being a major concern.image
PF795 EXPLORING THE REAL‐LIFE CLINICAL VALUE OF LOW DOSE DIRECT ANTICOAGULANTS FOR SECONDARY PREVENTION OF THROMBOEMBOLISM
Authors: Saul S. , McIlroy G. , Smith N. , Perrin D. , Fair S. , Kartsios C. 
Published: June 2019

Background:Anticoagulation is the mainstay of acute venous thromboembolism (VTE) therapy. Until recently Vitamin‐K antagonists (VKAs) were the standard of care for extended treatment of VTE. In the last decade, direct oral anticoagulants (DOACs) have been studied and approved for use in treatment and secondary prevention of VTE. The apixaban AMPLIFY‐EXTEND clinical trial and the rivaroxaban EINSTEIN CHOICE study, have offered evidence that low dose anticoagulation up to 12 months following completion of standard VTE treatment, can be equally effective to standard dose apixaban/rivaroxaban for secondary prevention of thromboembolism. To date there is no real‐life study recording the outcomes of patients on low dose DOACs in this setting.Aims:In this audit, we sought to identify patients on long term low dose apixaban/rivaroxaban for secondary prevention of VTE and record their outcomes.Methods:Between January 2015 and September 2018, 4,625 patients were initiated to DOACs in our clinics. Amongst them 394 patients were put on either apixaban 2.5 mg bd (N = 352) or rivaroxaban 10 mg od (N = 42). Their median age was 65(16–98) years. The index event to offer long term anticoagulation was unprovoked VTE in 271 patients while 123 had suffered a provoked VTE with permanent risk factors. Cancer‐associated thrombosis was recorded in 42 patients, 69 individuals had documented thrombophilia and/or family history of thrombosis. Recurrent VTE was recorded in 41 patients. The median time from thrombosis to low‐dose anticoagulation switch was 7.26(3–280) months. The median follow‐up time on low dose anticoagulation was 15(3–45) months.Results:Major bleeding occurred in 3/394 patients (0.76%), all 3 patients were on low dose apixaban. Major plus clinically relevant non‐major bleeding was recorded in 30 patients (7.6%). Recurrent VTE occurred in 13/352 patients (3.69%) in the apixaban group and 1/42 patients (2.3%) in the rivaroxaban group (p = NS). No statistical differences in bleeding rate and VTE recurrence were identified between the total patient population, the cancer related thrombosis and the thrombophilia/family history of VTE subgroup respectively (table).Summary/Conclusion:Our study although small, is the first to record the clinical experience of using long term low dose DOACs to prevent VTE recurrence in real life. Our results confirm that low dose DOACs are very safe with major bleeding rate oof <1% in 15 months. We did however find a higher incidence of recurrent VTE (3.55%) compared to the AMPLIFY‐EXTEND (1.7%) and the EINSTEIN CHOICE (1.2%) trials.image
PF804 SEC22B‐DEPENDENT TRAFFICKING IS ESSENTIAL FOR VWF MULTIMERIZATION AND FORMATION OF ELONGATED WPBS
Authors: Karampini E. , Jennifer O. , Geerts D. , Voorberg J. , Bierings R. 
Published: June 2019

Background:Von Willebrand factor (VWF) is a key hemostatic glycoprotein that is predominantly synthesized in endothelial cells. Upon synthesis, the pro‐VWF precursor dimerizes in the ER and is subsequently transported to the Golgi where it undergoes proteolytical processing, multimerization and finally is stored in newly emerging secretory organelles, known as Weibel‐Palade bodies (WPBs). Assembly of VWF into high molecular weight (HMW) multimers, packaging in elongated WPBs and regulated release to the extracellular environment as ultra‐long VWF strings is crucial for its ability to recruit platelets to sites of vascular injury. The adhesive properties of VWF are strongly tied to the length of the secretory organelles in which it's contained in, however, how endothelial cells control the dimensions of their WPBs is still unclear.Aims:In this study, we investigated the crucial role of SNARE‐mediated ER/Golgi trafficking in VWF maturation and WPB biogenesis.Methods:In a shRNA screen of longin‐containing SNAREs in primary endothelial cells, we identified the proteinsinvolved in ER/Golgi trafficking. Protein expression was assessed by Western Blot and the morphology of intracellular compartment was studied using confocal microscopy.Results:We found that silencing of Sec22b resulted in the loss of the typically elongated morphology of WPBs. VWF was partially retained in the ER, resulting in a significantly higher ratio of proVWF:VWF. Decreased VWF influx to the Golgi affected the morphology of both WPBs, that were short and “stubby”, as well as the trans‐Golgi network (TGN). In addition, downmodulation of Sec22b expression resulted in the absence of HMW VWF multimers. Overexpression of a dominant‐negative Sec22b variant lacking its SNARE domain confirmed these phenotypes, revealing that correct localization and/or function of Sec22B is important for VWF trafficking and WPB formation.Summary/Conclusion:Our data suggest that Sec22b is a novel regulator of VWF trafficking and WPB biogenesis that modulates VWF multimerization and the elongated shape of WPBs by controlling ER/Golgi VWF influx.
PF809 ARE NATIONAL GUIDELINES AND MANDATORY TRAINING ENOUGH TO ENSURE SAFE TRANSFUSION PRACTICE?
Authors: Lovato S. , Morganti E. , Gourgui‐Naguib H. , Sasidharan D. , Patel C. , Patel R. 
Published: June 2019

Background:Errors in administering blood product represent a risk for patient safety. The British Society of Haematology (BSH) published guidelines to promote safe transfusion practice (1). These guidelines states that should be recorded: the unique component donation number and the date, start time and the identification of the person administering the component.The guideline also sets the standard for monitoring the patient during the transfusion with pulse, temperature, respiratory rate and blood pressure at the start of the transfusion, after 15 minutes of the start and within one hour from the end.Transfusion training is mandatory for all health professionals involved in transfusion practice.Aims:The aim of this study was to establish if the guidelines established by BSH are applied in clinical practice across different departments.Methods:We performed a retrospective audit on transfusion documentation and patient monitoring and in a district general hospital. We included transfusion of red packed cells, platelets and fresh frozen plasma.Results:We identified 160 unit transfused (132 RPC, 16 PLTS and 12 FFP). Documentation of donation number and the date, start time and the identification of the person administering the component were complete in 88% of the cases, in 8% of the cases there was no documentation at all (Figure 1A); of the remaining in 80% of the cases was missing the signature of the administering person.Regarding the monitoring of the patient only 25% of the unit transfusions were monitored according to the guidelines, in 33% of the cases there was no documentation of the patient monitoring. The least monitored parameter was respiratory rate; the most frequent missed monitoring point was the one at the end of the transfusion (Figure 1B).Summary/Conclusion:Despite clear guidelines and compulsory training transfusion practice is still poor with more than a tenth of the transfusion being not fully documented in the notes and the number of transfusion episodes lacking adequate patient monitoring information outnumbering the transfusion monitored according to the guidelines (33% vs 25%).imagePerforming an audit across the entire hospital allowed us to identify the departments where transfusion procedures were not applied systematically with the plan to offer target training and re‐audit to improve transfusion practice.
PF810 ABO INCOMPATIBLE KIDNEY TRANSPLANTATION – ONE CENTRE EXPERIENCE
Authors: Sampaio M. , Antunes M. Bini , Malheiro J. , Dias L. , Martins L.S. , Pedroso S. , Almeida M. , Henriques A. Castro , Tafulo S. , Oliveira R. , Vasconcelos F. , Amil M. 
Published: June 2019

Background:Donor living kidney transplantation (KT) is an available optionfor end‐stage renal disease, improving survival and quality of life when compared with other treatments. ABO incompatibility was considered an important barrier for long but, with the increasing organ shortage and due to improvement of immunosuppression protocols, ABO‐incompatible (ABOi) KT has achieved remarkable success in the last decades, with graft survivals and patient overall survivals comparable to compatible transplantations. Consensually, initial goal is to lower patient ABO antibodies titter to ≤1:16 before transplantation, ≤1:8 during the first week and ≤1:16 during the second week after surgery. Thereafter, even a rebound of ABO antibodies does not appear to harm the graft due to accommodation phenomenon. Current strategies for desensitization include B‐cell‐depleting therapies and intensified immunosuppression as well as plasmapheresis to remove ABO antibodies.Aims:Retrospective evaluation of donor/recipient pairs proposed for ABOi Kidney transplantation between 2015 and 2018.Methods:Donor‐patient pairs were proposed by the Kidney Transplantation Centre. Patients were evaluated for ABO/Rh group, relationship with donor, diagnosis, pre‐KT isoagglutinin anti‐A and anti‐B (IgG and IgM), pre‐KT donor specific HLA antibodies, post‐KT isoagglutinin titter (daily up to D14, at D30, and at sixth month after KT), number of plasmapheresis performed (target: IgG isoagglutinin <1: 8 between D0‐D7 and <1:16 to D14), graft function titter (serum creatinine), transfusion support, significant associated complications and overall patient survival. An initial IgG isoagglutinin titter ≥1: 512 was considered contraindication for KT as well as the presence of donor specific anti‐HLA antibodies. Immunosuppression protocol included rituximab and basiliximab for B cell depletion and standard triple immunosuppression with tacrolimus, mofetil mycophenolate and corticosteroids.Results:We studied 43 donor‐receptor pairs for ABOi‐KT over a period of four years. Sixteen patients were excluded due to ABO IgG titters ≥1:512 and 10 out of 17 pairs considered suitable for transplantation were transplanted in the considered period.Results are summarized in table 1.Graft survival so far is 100% on a follow‐up period between 7 and 49 months. All patients are independent from dialysis and the creatinine level has steady levels (average of 1.61 mg/dL). However, in one patient a renal biopsy performed at sixteenth month documented an incipient glomerulopathy, even if ABO titters maintained low and no evidence of HLA Ab was found out.Summary/Conclusion:The presented results are in accordance with those described by some authors and confirm that ABOi KT is a viable alternative for the treatment of patients with chronic kidney disease, permit to expand the living donor pool and to reduce the time access to transplantation.image
PF817 INTENSIVE PLAN OF THERAPEUTIC PLASMA EXCHANGE IN PATIENT WITH EXTREME HYPERTRLIGLYCERIDEMIA DUE TO L‐ASPARAGINASE IN THE CONTEXT OF SMILE PROTOCOL IN T/NK NASAL LYMPHOMA TREATMENT
Authors: Sobejano E. , López‐Parra M. , Villar O. López , Higuero V. , Presa D. , Azibeiro R. , Rey B. , Fonseca M. , Avendaño A. , Carrilo J. , Rivera D. , de Ramón C. , Redondo A. , Yeguas A. , Baile M. , Mateos M.L. Martin , de la Calle V. Gonzalez , Díaz M. González , Vidriales M. 
Published: June 2019

Background:A 42 year‐old male patient was diagnosed in July 2018 of extranodal T / NK lymphoma, nasal type, EBV + CD56 +, IIA Stage, IPI 1, with right thigh mass and inguinal adenopathies. He received chemotherapy according to the SMILE protocol, that included dexamethasone, methotrexate, ifosfamide, etoposide and L‐asparaginase, starting in August 2018 together with local radiotherapy in the mass concomitantly. As a personal medical history, he was under treatment with Rosuvastatin for familial hypercholesterolemia and hypertriglyceridemia, that was well controlled.Aims:To prove that carry out an aggressive prophylactic apheresis schedule, allows to reduce the complications derived from hypertriglyceridemia due to L‐ASA and to administer full chemotherapy that entails greater possibilities of cure.Methods:One T/NK Nasal Lymphoma patient with familial dyslipidemia suffered multiple events of extreme hypertriglyceridemia (TAGs>1200) that required a total of twenty‐two therapeutic plasma exchanges (TPE) to be able to administer Lasparaginase.Results:During the first cycle after the 5th dose of L‐asparaginase the patient presents extreme hypertriglyceridemia (9016 mg /dl) and two TPE was done with very good response, TAGs of 511 mg/dl and 251 mg/dl after the 1st and 2nd apheresis, respectively. Due to it was an unexpected event, conservative management was performed and he did not receive the last two doses of L‐Asa. Due to the importance of L‐ASA,we optimized oral treatment and carried out an intense apheresis program since second cycle and every L‐ASA doses was received. The patient achieve completed metabolic response after the 3rdcycle. On the day +20 of the 6th cycle, coinciding with the last dose of L‐asa, it was decided not to make prophylactic plasma exchanges for TAG values of less than 1500 mg/dl (1361 mg /dl). 48 hours later he went to the emergency department and was diagnosed of acute acalculous pancreatitis in the context of hypertriglyceridemia secondary to L‐ASA (TAGs 7168 mg / dl). Two plasma exchanges were performed on days +23 and +24, with good response (decrease from 7168 to 580 TAGs).Summary/Conclusion:In patients with a family history of dyslipidemia maintain prophylactic apheresis until the administration of L‐asparaginase has been fully completed, maintaining <1000 TAG level is essential to improve the results.Moreover, an exhaustive follow‐up should be carried out in these patients, confirming 24 hours after the end of treatment that the TAGs value continues to be <1000 mg/dl and the patient is not at risk of developing pancreatitis.
S820 FRONTLINE BRENTUXIMAB VEDOTIN WITH CHEMOTHERAPY FOR STAGE 3/4 CLASSICAL HODGKIN LYMPHOMA: 3‐YEAR UPDATE OF THE ECHELON‐1 STUDY
Authors: Gallamini A. , Straus D. , Dlugosz‐Danecka M. , Alekseev S. , Illes A. , Picardi M. , Lech‐Maranda E. , Feldman T. , Smolewski P. , Savage K. , Bartlett N. , Walewski J. , Ramchandren R. , Zinzani P. , Connors J. , Jolin H. , Liu R. , Fenton K. , Josephson N. , Radford J. 
Published: June 2019

Background:The phase 3 ECHELON‐1 study (NCT01712490) demonstrated that brentuximab vedotin with doxorubicin, vinblastine, and dacarbazine (A+AVD) was superior to doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), in terms of modified progression‐free survival (PFS) per independent review and per investigator, for the frontline treatment of stage 3/4 classical Hodgkin lymphoma (cHL) (Connors JM, et al. N Engl J Med 2018;378: 331–344). The RATHL, and SWOG S0816 studies utilized positron‐emission tomography (PET) scan‐adapted strategies performed after cycle 2 (PET2), demonstrating short‐ and long‐term toxicities in PET2‐positive (PET2+) patients switched to bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP), or escalated BEACOPP, and frequent relapses in PET2‐negative (PET2‐) patients. Long‐term follow‐up of patients with stage 3/4 disease who were aged ≤60 years in the RATHL and SWOG S0816 studies demonstrated 3‐year PFS of 79.8% (PET2‐, 82.1%), and 5‐year PFS of 74% (PET2‐, 76%), respectively.Aims:Here we present a 3‐year update of the ECHELON‐1 study to compare the effects of frontline A+AVD vs ABVD in patients with stage 3/4 cHL, including PFS per investigator and outcomes by PET status for the intention‐to‐treat (ITT) population.Methods:Patients with stage 3/4 cHL were randomized 1:1 to receive up to six cycles of A+AVD (n = 664) or ABVD (n = 670). Interim PET2 was conducted, patients with Deauville score of 5 at PET2 were allowed to switch to an alternative therapy. All analyses of PFS are exploratory and per investigator assessment.Results:At a median follow‐up of 37 months, analysis of PFS in the ITT population favored the A+AVD treatment arm (Table), with a 3‐year PFS of 83.1% for A+AVD vs 76.0% for ABVD; the 3‐year PFS values for PET2‐ patients aged <60 years were 87.2% vs 81.0%, respectively. A trend toward benefit for PET2+ patients aged <60 years treated with A+AVD was also observed, with a 3‐year PFS of 69.2% vs 54.7% with ABVD.Data from subgroups, together with safety follow‐up, including for peripheral neuropathy, will be presented.Summary/Conclusion:Follow‐up at 3 years demonstrates that frontline treatment of stage 3/4 cHL with A+AVD provides a durable treatment benefit compared with ABVD that is independent of PET2 status. While direct comparisons cannot be made, efficacy with A+AVD appears favorable in the context of findings with PET‐adapted strategies, without requiring interim PET assessment, escalation of therapy, or bleomycin.image