Journal articles on the topic 'Dresden / Medien@age'

Objective: The purpose of this paper is to describe a minimally invasive chronic Achilles tendon rupture reconstruction combining a modified Dresden technique and endoscopic flexor hallucis longus (FHL) tendon transfer. Methods: Our prospectively collected database was queried for patients presenting with chronic Achilles tendon rupture. Patients were included if they presented any of the following criteria: more than 65 years of age, history of previous DVT, active smoking habit and Diabetes. Pre and post-operative SF-36 and AOFAS hindfoot scores, complications, and patient satisfaction grades were recorded. Results: Eight patients met the inclusion criteria; the median age was 49 years old (range 22 - 67 years). Two complications were registered (sural neuritis and minor wound dehiscence). Mean AOFAS score increased from 48 (range 40 - 63) to 91,6 (range 85 - 95). Regarding SF-36 score, the SFF-36 improved from 51,6 to 79,3 points and the SFM-36 enhance from 25 to 61,5 points. All patients evaluated their satisfaction regarding the performed procedure as satisfactory. Conclusion: Chronic Achilles tendon rupture reconstruction combining a modified Dresden technique and endoscopic FHL transfer is an attractive option in high-risk patients, with favorable results at the short-term follow-up. Level of Evidence IV; Therapeutic Study; Case Series.

Abstract Background: The effectiveness and safety of acute venous thromboembolism (VTE) treatment with rivaroxaban, demonstrated in phase-III trials, needs to be evaluated in unselected patients treated under daily care conditions. Patients and methods: The Dresden NOAC registry is a prospective regional registry in which patients with oral anticoagulation undergo prospective follow- up (FU). So far, more than 3200 patients have been enrolled, including 772 VTE patients with rivaroxaban treatment. For this analysis, only patients with acute VTE who started rivaroxaban within 14 days after diagnosis of VTE and who were enrolled within these 14 days were evaluated with regard to patient characteristics, treatment persistence and clinical outcomes. All reported outcome events were centrally adjudicated based on source documentation and standard definitions. Results: Between December 1st 2011 and March 31st 2016, 407 patients received rivaroxaban for acute VTE treatment (51.6% female, 80.8% DVT; 19.2% PE±DVT, mean age 61.4 years). Mean time between VTE diagnosis and initiation of rivaroxaban was 1.7±3.3 days (median 0d; 25th/75th percentile 0; 1d). At baseline, rivaroxaban doses consisted of 15 mg BID in 93.1%, 20 mg OD in 3.4%, 15 mg OD in 3.2% and 10 mg OD in 0.2% of patients. Reasons for not using 2x15 mg rivaroxaban BID were pre-treatment with therapeutic parenteral anticoagulants for ≥7 d in 14 cases, comorbidities (e.g. bleeding history, renal impairment) in 4 cases and unknown in 10 cases. During FU (mean 762.4±462.7d), the mean rivaroxaban exposure was 357.7±385.9 days. During treatment with rivaroxaban, 4/407 patients (1.0%) experienced a recurrent VTE, which translated into a recurrence rate of 1.0/ 100 pt. years. During treatment, 172/407 (42.3%) patients reported bleeding complications, which in 13 cases (3.2%; 3.3/100 pt. years) were major bleeding according to ISTH definition, including one fatal intracranial bleeding. Patients with deep vein thrombosis (DVT) and pulmonary embolism (PE) had similar rates of recurrent VTE during rivaroxaban treatment (1.01 and 1.01/100 pt. years) but PE patients had numerically higher rates of major bleeding (3.99/100 pt. years compared to 3.09/100 pt.years in the DVT group). Effectiveness and safety profiles were consistent across relevant subgroups (table 1). 18 patients died during FU (2.12/100 pt.years), of which 8 deaths occurred during or within 3 days after last intake of rivaroxaban. Most common causes of death were fatal cardiovascular event (n=7) and terminal malignant disease (n=4), followed by sepsis/infection (n=3), age related death (n=1), fatal bleeding (n=1) and other reasons (n=2). At 6 months (FU completed in 365 pts.), 61.4% of patients were still taking rivaroxaban. The remaining patients had a scheduled end of treatment (28.8%) or were switched to other anticoagulants (7.1%). Therefore, the rate of unplanned complete discontinuation at 6 months was 2.7%. At 12 months (FU completed in 289 pts.), 41.5% of patients were still taking rivaroxaban. The remaining patients had a scheduled end of treatment (45.0%) or were switched to other anticoagulants (8.3%). Therefore, the rate of unplanned complete discontinuation at 12 months was 5.2%. After rivaroxaban interruption for more than 3 days or permanent discontinuation, 21 patients experienced a recurrent VTE (9 PE±DVT, 12 DVT) with a mean time between last intake of rivaroxaban and VTE recurrence of 351.2±282.6 days (range 7-926d). PE was a common manifestation of VTE recurrence and, despite numerically lower bleeding rates after discontinuation, 2 cases of intracranial haemorrhage occurred (table 2). Conclusions: In unselected patients in daily care, rivaroxaban treatment for acute VTE has high effectiveness and acceptable rates major bleeding. Initial dosing was according to label in over 90% of patients and, at 6 and 12 months, persistence to rivaroxaban therapy was excellent with low rates of unplanned complete discontinuation. Fatal VTE and fatal bleeding are rare events during rivaroxaban therapy and all-cause mortality is mostly related to underlying diseases, age or acute co-morbidities. Treatment discontinuation resulted in a relevant increase in VTE recurrence, of which more than 40% manifested as PE. In contrast, major bleeding rates declined after discontinuation but with 1%/year remained at a clinically relevant level, probably due to co-morbidities. Disclosures Marten: Bayer: Honoraria; Daichii Sankyo: Honoraria. Werth:Pfizer: Honoraria; Bayer: Honoraria; Boehringer Ingelheim: Honoraria; Daiichi Sankyo: Honoraria; OmniaMed: Honoraria; LEO-Pharma: Honoraria. Beyer-Westendorf:Pfizer: Consultancy, Honoraria, Research Funding; Boehringer Ingelheim: Consultancy, Honoraria, Research Funding; Daichii Sankyo: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Honoraria, Research Funding; LEO: Consultancy, Honoraria, Research Funding.

144 Background: In Germany specialised palliative care in outpatient setting is financed by health insurances since 2007. Home Care Sachsen e.V. is a specialised palliative care provider working with two palliative care teams including qualified nurses, physicians and social workers in closely cooperation with general practitioners and nursing services. We report about the results of our work in a rural area around Dresden in Saxony, Germany. Methods: Our data were collected prospectively with PalliDoc software. Results: Between 2011 – 2013 Home Care Sachsen e.V. served for 1,572 pts (888 m, 684 f); 93% with an oncologic disease. Median age was 71 y, Karnofsky index was 40%, median caring time 27 days. In this time, 25% of our pts had one stay in hospital, 8% two and 4% three and more. 63% had no stays in hospital. At least 1,271 pts. died: 65% at home; 9% in nursing homes and hospices; 15% in palliative care units and 11% in hospital. Conclusions: Mean home death rate of oncologic pts without intervention in Germany is about 44% (Papke J, Koch R: Places of Death from Cancer in a Rural Location. Onkologie (2007) 30, 105-08). This proportion could be enhanced considerably with outpatient palliative care. Providing of specialised palliative care with a multiprofessional team is effective to increase the rate of dying at home and to fulfill one of the strongest wishes of pts in a palliative situation.

Abstract Background : Bleeding is a common complication of oral anticoagulation (OAC). In anticoagulated women of child-bearing potential (WOCBP), increase of menstrual bleeding may be discomforting and severe cases of menorrhagia may require dedicated treatment or even discontinuation of OAC. Since hypermenorrhea seems to be more frequent in patients receiving direct oral anticoagulants (DOAC) compared to classic OAC with vitamin-K antagonists, patterns of menorrhagia need to be studied in daily care cohorts. Patients and methods: Using data from the prospective, non-interventional Dresden NOAC registry and phase-III DOAC trial patients at our site, we evaluated rates, severity and management of vaginal bleeding complications in WOCBP (defined as age ≤55 years and without sterilizing procedures or age >55 years with documented menstrual bleeding). All bleeding complications were centrally adjudicated and classified according to ISTH definition. Annualized rates of vaginal bleeding and hypermenorrhea were calculated as number of bleeding events divided by cumulative days of DOAC exposure divided by 365 days. OAC treatment satisfaction was assessed in all registry patients at every follow-up visit by a simple six-graded scale (ranging from 1=very satisfied to 6=very unsatisfied). To assess impact of vaginal bleeding on quality of live, the first available score after a vaginal bleeding was compared with the last available score of WOCBPs without vaginal bleeding. Results: Until March 31th 2015, 1343 women were enrolled, of which 154 were WOCBPs (mean age 39±12 years; range 14-56). In these patients, OAC consisted of dabigatran (1.3%), rivaroxaban (92.2%), apixaban (5.8%) or edoxaban (0.6%). During follow-up (mean FU duration 24.6 months), 85 female patients reported 107 vaginal bleeding complications, of which 68 occurred in 53 WOCBPs (53 cases of hypermenorrhea and 15 bleedings unrelated to cycle). Table 1 indicates severity of hypermenorrhea and vaginal bleedings unrelated to cycle. According to ISTH definition, 37/68 (54.4%) of the vaginal bleeding in WOCBPs were minor, 25/68 (36.8%) were non-major, clinically relevant (NMCR) and 6/68 (8.8%) major bleeding (classified as "major" due to drop of hemoglobin ≥2g/l in 5 cases and/or transfusion of ≥2 units of red blood cells in 5 cases). In relation to all exposed WOCBPs, the rate of vaginal bleeding events was found to be 0.41 events per exposure year and the rate of hypermenorrhea was found to be 0.32 events per exposure year (median exposure time 243d; 25th/75th percentile 105/674d and median time to first hypermenorrhea 26d; 25th/75th percentile 10/46d). Of the 53 WOCBPs that described vaginal bleeding complications (including hypermenorrhea and cycle-unrelated bleeding), 12/53 (22.6%) experienced a 2nd and 3/53 (5.7%) a 3rd event (figure 1). While bleeding intensity remained stable in most recurrent events, bleeding intensity increased in 6 cases with a 2nd bleeding episode while bleeding intensity remained stable or decreased in all 3 cases with a third episode. In only 16 of the 53 hypermenorrhea events, anatomical causes could be established and 3 of these cases progressed to major bleeding (necessity of at ≥2 units of red blood cells). In contrast, in the 34 hypermenorrhea events without anatomical causes, bleeding intensity was less severe (table 1). Surgical or interventional treatment was necessary in 6/68 (8.8%) vaginal bleeding events. The remaining 62 (91.2%) events were treated conservatively (start or change of hormone therapy, tranexamic acid, OAC dose reduction or temporary interruption). Overall, OAC treatment satisfaction in WOCBP was good (mean score 1.6; 25th/75th percentile 1/2 with data available for 98/154 WOCBPs) and not different in patients with and without vaginal bleeding complications (1.6; 25th/75th percentile 1/2 vs. 1.5; 1/2; p=0.548). Conclusion : Vaginal bleeding and especially hypermenorrhea is a common complication in WOCBPs receiving oral anticoagulation. Only a small proportion of affected patients have underlying anatomical causes for bleeding but these patients often develop more severe bleeding. The majority of cases can be conservatively managed and bleeding intensity rarely increases over time. Overall, the impact of vaginal bleeding complications on treatment satisfaction seems small. Disclosures Marten: Bayer HealthCare: Honoraria. Beyer-Westendorf:Pfizer: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Boehringer Ingelheim: Honoraria, Research Funding; Bayer HealthCare: Honoraria, Research Funding.

Abstract Background : Peripheral blood progenitor cells (PBPCs) are routinely applied worldwide for allogeneic related and unrelated stem cell transplantation. Factors influencing the mobilisation of PBPC’s in healthy donors are poorly understood. The database of the Apheresis Centre at the University of Dresden was evaluated to identify predictors of PBPC mobilisation. Methods : 4050 PBPC collections (3928 first donations, 122 second donations) of healthy unrelated donors between 1/1996 and 1/2008 were carried out according to a standardized protocol and prospectively documented in a database. Peripheral blood CD 34 counts were performed before each leukapheresis. CD 34 yield of every PBPC product was calculated in absolute numbers and per kg body weight of the recipient. All parameters are presented as median and range. Mann-Whitney test was performed for discrete variables. Correlation analysis by Pearson was applied for continuous variables. Multivariate regression analysis was carried out to detect factors independently predicting mobilization efficacy. Results : The range of peripheral CD 34+ haematopoietic stem cells obtained on day 5 was 8.7–285/μl (median 67.5/μl) in male and 6–282/μl, (median 51/μl) in female donors. The median CD 34 yield from the first leukapheresis was 5.88 ×108. Inadequate CD34-yields (< 2 × 106/kg) were obtained only in 18 donors (0.45%). Peripheral CD 34 count at day 5 is significantly correlated with (positive linear regression): BMI, baseline platelet count, male sex, G-CSF application (split dose), baseline leukocyte count. Peripheral CD 34 count at day 5 correlates negatively with: female sex, single dose G-CSF application, regular alcohol consumption and regular smoking status. Linear regression analyses revealed no significant influence of donor age. Multivariate correlation analysis included sex, BMI, baseline platelets, G-CSF-application, baseline leukocytes, age and smoking. This model explained 21.2 % of the variabilityA strong correlation exists between peripheral CD 34-counts at day 5 and apheresis yield (70% of the variability explained). Conclusions : A dose of 7.5 μg/kg/d lenograstim proved to be safe and effective in a large cohort of unrelated donors for mobilizing sufficient haematopoietic progenitor cells for allogeneic transplantation. Our analysis of 4050 donations revealed significant, but very weak correlations of the peripheral CD 34-counts with donor characteristics and life style parameters. No single parameter derived from donor baseline investigation reliably predicts CD 34 yield. Further evaluation of healthy donors including comprehensive genomic linkage analysis is necessary to elucidate the variable efficiency of PBPC mobilization

Abstract Background: The most common side effects of oral anticoagulants are bleeding complications. In large trials, direct oral anticoagulants (DOAC) have been shown to reduce the risk of major bleeding compared to warfarin. However, little is known about the management and outcome of survivors of major DOAC bleeding. Patients and methods: Using data from the prospective, non-interventional Dresden NOAC registry, we evaluated the management and outcome of survivors of major DOAC bleeding. All DOAC bleeding complications were centrally adjudicated and classified according to ISTH definition. For this analysis, every ISTH major bleeding was identified in the database and for each case, the first major bleeding was evaluated. Restart of oral anticoagulation (OAC) 30 days after major DOAC bleeding was assessed and the impact of restart on the composite endpoint of (recurrent major bleeding, stroke, TIA, systemic embolism, venous thromboembolism) or survival was evaluated using Kaplan-Meier time-to-first event estimation. Results: Until January 31th 2015, 2771 patients were enrolled into the registry (1898 treated with rivaroxaban, 525 apixaban and 348 dabigatran). During follow-up (mean follow-up duration 23.6 months) 127 patients developed 170 ISTH major bleeding events during DOAC exposure (drop of hemoglobin ≥2g/l in 106 (62.4%) cases, transfusion of ≥2 units of red blood cells in 105 (61.8%) cases, critical site bleeding in 43 (25.3%) cases and/or fatal outcome in 9 cases (5.3%)). Of the 127 patients with major bleeding (mean age 77±11 years; range 37-94), 53.5% were male the median HAS-BLED score was 2 (25th/75th percentile 1/2, range 0-5). The majority major bleeding events occurred spontaneously (64.6%). In contrast, 14.2% major bleeding events occurred after trauma and 21.3% occurred after surgical or interventional procedures that were performed during treatment or within 3 days after last DOAC intake. Most common sites of bleeding were gastrointestinal tract (37%), diffuse bleeding during or after surgery (15.7%), intracranial (11%), skin/mucosal (9.4%), intraocular (8.7%), genitourinary (7.9%), intraarticular bleeding (6.3%) and bleeding in other sites (4%). 85 cases lead on to a hospitalization (mean duration 9±7d) and 11 cases were managed as outpatient. The remaining 31 bleeding events occurred during a hospital stay. The majority of cases were managed with surgical or interventional treatment (55.9%; mainly endoscopic treatment for gastrointestinal bleeding. In 75 (57.1%) cases red blood cell transfusion was given and 11 (8.7%) of cases received fresh frozen plasma. Furthermore, 15 (11.8%) of cases received PCC and 4 (3.1%) fibrinogen. The restart of OAC (DOAC or vitamin K antagonists; VKA) was assessed at day 30 after major bleeding. While OAC was restarted in 80 patients (63%) it was not restarted 30 days after bleeding in the remaining 47 (37%). Patients who restarted OAC had a similar mean age (76 vs. 78y, p=0.309) and a similar mean HAS-BLED score (1.8 vs. 2.1, p=0.115) compared to patients who did not restart OAC. During follow up after bleeding (mean follow-up duration 15.2 months), the rate of combined endpoint of recurrent major bleed and thromboembolism was significantly lower in patients that restarted OAC compared to those who did not restart (14.7/100 patient years; 95%-CI 8.0-24.7 vs. 38.6/100 patient years; 21.1-64.7; p=0.0342). All-cause mortality was found to be 23.9/100 patient years (95% CI 16.9-32.8). Mortality was significantly lower in patients that restarted OAC compared to those who did not restart (16.4/100 patient years [9.7-25.9] vs. 40.6/100 patient years [24.8-62.7]; p=0.0099). Most common cause of death was fatal cardiovascular event (12/38, 31.6%) and fatal bleeding (9/38, 23.7%) followed by terminal malignant disease (6/38, 15.8%), infection/sepsis (6/38, 15.8%) and age related death (5/38, 13.2%). Conclusion: Even in cases with major DOAC bleeding, acute mortality is low with a case-fatality rate of 5.3%. Furthermore, OAC is restarted within 30 days after major bleeding in only 63%. Patients who restarted OAC had significantly lower rates of the combined endpoint of thromboembolism or recurrent major bleeding and had a significantly better survival. Therefore, benefits of OAC continuation may outweigh the risks even in patients with major DOAC-related bleeding. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Marten: Bayer HealthCare: Honoraria. Beyer-Westendorf:Bayer HealthCare: Honoraria, Research Funding; Boehringer Ingelheim: Honoraria, Research Funding; Bristol- Myers Squibb: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding.

This study investigated the effect of weaning age on carcass characteristics of crossbred piglets reared up to 70 kg body weight (BW) under intensive system. A total of 24 piglets were used in a completely randomized design. The experiment comprised three treatments: piglets weaned at 21, 28, and 35 days of age with four replicates each with two piglets (castrate and female). At 70 kg BW two piglets (castrate and female) were randomly selected from each replicate and sacrificed for carcass evaluation. Hot carcass weight (HCW) was measured and thereafter dressing out percentage was calculated. Carcasses were chilled at 7 0C for 24 hours to determine cold dressed weight (CDW). Carcasses were cut into the left and right halves along the median line. The left half of the carcass was used to measure carcass length (CRLTH), average backfat depth and longissimus muscle area (LMA) at the 10th rib, while the right half of the carcass was physically dissected into bone, muscle and fat and thereafter tissue ratios calculated. Longissimus muscle was removed at the 10th and 11th ribs from the left half of the carcass for chemical composition analysis. Data were analysed using General Linear Model. Weaning age had no influence (p > 0.05) on HCW, dressing percentage, CDW, CRLTH, average backfat thickness, average backfat depth, LMA and carcass lean percentage. No significant differences (p > 0.05) were observed on average percentages of bone, muscle and fat tissue and their tissue ratios. Weaning age did not influence (p > 0.05) moisture, protein, fat and ash contents of the meat. In addition, weaning age had no (p > 0.05) effect on carcass characteristics, physical and chemical body composition of meat. These results indicate that piglets can be weaned at 21, 28 and 35 days of age without detrimental effects on carcass characteristics, physical and chemical body composition of pork.

Abstract Introduction In both partial thickness burns and skin graft donor sites, coverage with Polylactide-based copolymer dressing (PLBC dressing) has been shown to result in expedited healing and improved pain outcomes when compared to more traditional techniques. These advantages are generally attributed to the way in which PLBC remains as an intact coating over the wound bed throughout the healing process, protecting wounds from the contamination and microtraumas associated with changes more conventional dressings. At our institution, we began selectively utilizing PLBC as a means of securing and protecting fresh skin graft, in hopes that we would find similar benefits in this application. Methods Clinical Protocol-- The PLBC dressing was used at the attending surgeon’s discretion. In these cases, meshed STSG was placed over prepared wound beds. Staples were not utilized. PLBC dressing was then placed over the entirety of the graft surface, securing graft in place by adhering to wound bed through intercises. (Staples were not used.) The graft and PLBC complex was further dressed with a layer of non-adherent cellulose based liner with petroleum based lubricant, and an outer layer of cotton gauze placed as a wrap or bolster. Post operatively, the outer layer (“wrap”) of gauze was replaced as needed for saturation. The PLBC and adherent “inner” liner were left in place until falling off naturally over the course of outpatient follow-up. Retrospective Review-- With IRB approval, patients treated PLBC over STSG between April 2018 to March 2019 were identified via surgeon’s log and pulled for review. Documentation gathered from operative notes, progress notes (inpatient and outpatient) and clinical photography was used to identify demographics, mechanism of injury, depth, total body surface area percentage (TBSA%), size of area treated with PLBC dressing, graft loss, need for re-grafting, signs of wound infection, antibiotic treatment, and length of stay. Results Twenty-two patients had STSG secured and dressed with PLBC. Median patient age was 36.5 years. Median TBSA was 5.1%, and median treated area 375 cm2. Follow up ranged from 21 to 232 days post-operatively, with two patients lost to follow up. All patients seen in outpatient follow up were noted to have “complete graft take” or “minimal” graft. None of the areas treated with PLBC dressing required re-grafting. There were no unplanned readmissions, and no wound infections were diagnosed or treated. Practitioners in in-patient setting and in follow up clinic reported satisfaction with the PLBC dressing. Conclusions The PLBC dressing was a feasible solution for securing and dressings STSGs. Future work is needed to determine whether its use is associated with an improvement in patient outcomes.

Cadmium (Cd) concentrations in 1663 liver, 1779 kidney and 2526 muscle samples were measured in a residue survey organised by the Australian Bureau of Rural Science at meatworks throughout Australia. Cadmium concentrations in livers and kidneys were also determined in sheep ranging in age from newly born to 112 months of age which had been grazed throughout life at high or low stocking rates on an improved pasture dressed annually with superphosphate. Concentrations of Cd in the residue survey averaged (with median) 0.30 (0.11), 0.96 (0.28) and 0.03 (0.01) mg/kg freshweight in ovine liver, kidney and muscle respectively; the corresponding values in cattle were 0.18 (0.08), 0.65 (0.24) and 0.03 (0.01) mg/kg. Concentrations in liver and kidney were greater in older than in younger animals, at high than at low stocking rates, and in South and Western Australia than in other States. Cadmium concentrations increase with age because ruminants are born with a low Cd burden, and much of the Cd ingested and absorbed thereafter is retained as Cd-metallothionein in the liver and kidney. It is postulated that differences in Cd levels between geographical regions, species and stocking rate are partially due to the consumption of soil that had been fertilised with superphosphate containing Cd. Hepatic and renal Cd concentrations were highly correlated and were assumed to reflect Cd intake; correlations with copper concentrations were generally small. Eight per cent of kidneys exceeded maximum permissible Cd concentrations for human consumption (2.5 mg/kg), but only 2% of liver and 1% of muscle samples exceeded the statutory maxima (1.25 and 0.2 mg/kg respectively).

Abstract Abstract 357 Introduction: Molecular predictors for treatment outcome after allogeneic hematopoietic stem cell transplantation (HSCT) of MDS and AML patients are limited. Recently, mutations in the splicing gene machinery have been described as frequent aberrations in MDS. The aim of this study was to investigate the prognostic impact of mutations in the splicing genes U2AF1, SRSF2 and SF3B1 in a large cohort of patients with high risk MDS or secondary AML following MDS (sAML) undergoing allogeneic HSCT. Patients and Methods: Patients (n=339) with a diagnosis of MDS (50.1%) or sAML (49.9%) who received allogeneic HSCT at four German university medical centers (Dresden, Düsseldorf, Hamburg and Hannover) between 1996 and 2011 and for whom genomic DNA was available from a time when the disease was active, were evaluated for the presence of mutations in the splicing genes U2AF1, SRSF2, and SF3B1 by direct sequencing. Results: Median follow up from time of transplantation was 3.27 years. Median patient age at time of HSCT was 58 years (range 19–74). 74 patients (21.8%) were in complete remission and 265 patients (78.2%) had active disease before transplantation. Low, intermediate, and high risk cytogenetics according to IPSS were found in 204 (60.2%), 42 (12.4%), and 76 (22.4%) patients, respectively (in 5% cytogenetic information was not available). Related donor HSCT was performed in 82 patients (24.2%), and unrelated donor HSCT in 257 patients (75.8%). Myeloablative preparative regimens were used in 51 patients (15%), and a non-myeloablative regimen was given to 288 patients (85%). Mutations in U2AF1, SRSF2 and SF3B1 were detected in 14 (4.1%), 32 (9.4%) and 18 (5.3%) patients, respectively. SRSF2 and SF3B1 mutations co-occured in two patients, while the other patients had not more than one mutation in the investigated genes. Baseline characteristics were similarly distributed between U2AF1, SRSF2, or SF3B1 mutated and wildtype patients, respectively (sex, MDS vs sAML, cytogenetics, CMV status of patient, type of previous treatment, and remission status prior to transplantation), except a higher median age of U2AF1 mutated compared to wildtype patients (P=.02). There were no differences regarding transplant-related characteristics between patients with mutated or wildtype U2AF1, SRSF2, and SF3B1 (reduced intensity vs standard conditioning, GvHD prophylaxis, donor age, donor sex, CMV and HLA compatibility between recipient and donor). U2AF1 mutations were associated with a significantly shorter overall survival (OS, median 0.58 vs 3.6 years in mutated vs wildtype patients, respectively, HR 2.54; 95%CI 1.41–4.58; P=.002). The cumulative incidence of relapse (CIR) was higher in U2AF1 mutated compared to wildtype patients (3-year CIR 50% vs 22%, P=.002), while non-relapse mortality (NRM) was similar between mutated and wildtype patients (3-year NRM 43% vs 29%, P=.11). Mutations in SRSF2 and SF3B1 were not associated with OS (P=.98 and P=.44, respectively), CIR (P=.19 and P=.19, respectively), and NRM (P=.49 and P=.44, respectively). In multivariate analysis, when considering variables with P<.15 in univariate analysis (age above or below 55 years, karyotype, stage [MDS vs sAML], CMV serostatus of patient, donor type [related vs unrelated], donor sex), U2AF1 mutations independently predicted shorter OS (HR 2.6; 95%CI 1.39–4.85; P=.011) besides karyotype, stage, CMV serostatus, and donor sex. Mutations in U2AF1 independently predicted higher CIR in multivariate analysis (HR 3.02, 95% CI 1.36–6.7, P=.007). The rates of acute and chronic GvHD were similar in U2AF1 mutated and wildtype patients. Summary: U2AF1 mutations independently predicted worse patient outcome after allogeneic HSCT in MDS and sAML patients in our study due to a higher incidence of relapse. The U2AF1 mutation status may become useful to identify patients at high-risk for relapse after transplantation independent of established prognostic factors. Disclosures: Platzbecker: GlaxoSmithKline: Honoraria, Research Funding.

Abstract The t(8;21) is associated with high complete remission (CR) rates and high survival rates after cytarabine-containing postremission therapy for AML. However, patients with leukocytosis and additional cytogenetic abnormalities, such as loss of sex chromosome (LOS), have worse outcomes. We compared patients ages 16 to 60 years with t(8;21) AML in first CR, comparing 132 patients receiving postremission chemotherapy (chemo) with 118 receiving HLA-identical sibling HCT. The chemo cohort included patients treated with double induction followed by cytarabine-containing regimens in one of eight different German AML Intergroup clinical trials (SHG-Hannover-AML-2/95, SHG-Hannover-AML-1/99, SHG-Dresden-AML-96, AMLHD93, AMLHD98A, AMLCG92, AMLCG99, OSHO-AML-96) between 1993 and 2002. HCT recipients were registered with the CIBMTR from 1990 to 2000. To adjust for potential bias caused by delayed entry in the transplant cohort, left-truncated univariate analysis and Cox multivariate models were used. The median age of patients undergoing chemo and HCT were 42 and 32 years of age, respectively (p&lt;0.001). The table below shows five-year outcomes in months, including relapse rate, treatment related mortality (TRM), adjusted leukemia free survival (LFS) and adjusted overall survival (OS) according to multivariate analysis (Table). WBC &gt; 25.4×109/L was associated with higher relapse risk (RR=2.09, P=0.03), shorter LFS (RR=1.9, P=0.008) and shorter survival (RR=1.91, P=0.012), independent of postremission treatment. Neither year of treatment nor specific chemotherapy protocols were significantly associated with outcomes. HCT and chemotherapy had similar overall survival in patients with LOS and leukocytosis; in those without LOS, survival was significantly higher with chemotherapy. In this cohort of patients with t(8;21) treated in the 1990s, high transplant related mortality offset the antileukemia benefit of HCT, suggesting that HCT be reserved for patients who fail postremission chemotherapy. TRM (95% CI) Relapse (95% CI) LFS (95% CI) OS (95% CI) LOS No LOS *From multivariate models Chemo 6 (2–11) 29 (21–37) 64 (55–73) 55 (41–69) 84 (74–92) HCT 32 (22–44) 14 (8–21) 55 (45–65) 64 (50–77) 53 (39–67) P-value* &lt; 0.001 0.01 0.24 0.74 0.002

Abstract Aberrations of the MLL gene on chromosome 11q23 occur in about 5–10% of adult patients with acute myeloid leukemia (AML). Most commonly, fusion of the MLL gene to the genes AF9 on chromosome 9 or AF6 on chromosome 6 are found resulting in the translocation t(9;11) and t(6;11), respectively. The remaining patients with aberrations of chromosome 11q23 constitute a heterogeneous group with numerous fusion partners. This genetic heterogeneity hampers risk stratification of these patients. Accordingly, AML patients with 11q23 aberrations have varyingly been stratified as intermediate or high risk patients by different study groups. To analyze the impact of different 11q23 aberrations on the prognosis of AML patients up to 60 years, a pooled data analysis of 5 consecutive studies for the treatment of adult AML patients was performed. All patients received double induction treatment with araC and an anthracycline followed by an intensive consolidation with either a high dose araC based chemotherapy regimen or an autologous or allogeneic stem cell transplantation. In total, 137 patients with 11q23 aberrations were identified by cytogenetics and/or molecular techniques. 51 patients (37%) had a t(9;11), 19 patients (14%) a t(6;11), 8 patients (6%) a t(11;19), 6 patients (4%) a t(11;17) and 5 patients (4%) a t(10;11). 48 patients (35%) hold other fusion partners or deletions of 11q23. For further evaluation, patients harbouring other 11q23 aberrations than t(9;11) and t(6;11) were grouped together. Median age of all patients was 39 years (range 16–60). Overall complete remission rate was 75% with no significant difference between the groups (82% for t(9;11), 74% for t(6;11) and 70% for others). Altogether, 9% of the patients had treatment failure and 8% died during induction. Relapse-free survival (RFS) and overall survival (OS) at 5 years for the entire group was 34% and 28%, respectively. RFS and OS of the t(6;11) group was 0% and 11% respectively and thus was significantly inferior to patients with t(9;11) (RFS: 48%, OS: 33%) and patients with other 11q23 aberrations (RFS: 32%, OS: 28%). Within the t(9;11) group there was no difference in RFS or OS between patients who had a t(9;11) as a sole aberration (n=35) and patients with additional aberrations (n=16). Moreover, in t(9;11) no difference in RFS was observed between treatment with high dose araC, autologous or allogeneic stem cell transplantation as late consolidation. In conclusion, these data demonstrate that prognosis of patients with 11q23 is heterogeneous. Patients with t(9;11) have a relatively good outcome independent of the consolidation therapy used. In contrast, the prognosis of patients with t(6;11) is extremely poor. Therefore, patients with t(6;11) should be regarded as high risk and alternative treatment strategies for this subgroup are required.

Abstract Introduction Total (-7) or partial (7q-) monosomy 7 is frequent in malignant myeloid disorders, observed in around 12% of MDS/AML and up to 40% of therapy-associated MDS/AML. Monosomy 7 is associated with poor outcome, high susceptibility to infections and poor response to chemotherapy. A therapeutic benefit for 5-azacytidine was previously described (Fenaux et al., 2009). The present study was designed to analyze clinical features, prognosis and response to different therapeutic strategies in patients with monosomy 7 in a multicentric, retrospective German cohort study. Patients and methods Currently, 231 patients with MDS/AML following MDS and monosomy 7 were included. Inclusion criteria were defined as follows: Morphologic diagnosis of MDS/AML following MDS, age ≥18 years, bone marrow blast count ≤30% and presence of -7 or 7q-. The data was assembled from centers in Düsseldorf, (n=120; 52%), Cologne (n=38; 17%), Freiburg (n=31; 13%), Göttingen (n=14; 6%), Munich (n=13; 6%), Dresden (n=11; 5%) and Mannheim (n=4; 2%). The median age in the study cohort was 67 years, 65% of patients were males. 29/231 patients (13%) were diagnosed as AML following MDS. MDS/AML was therapy-associated in 24 patients (11%). Regarding IPSS, 38 (19%) were classified as low/intermediate 1 risk and 165 (81%) as intermediate-2/high-risk. According to IPSS-R, 2 (1%) were assigned to the very-low/low risk group, 31 (16%) to the intermediate group, 52 (27%) to the high-risk group and 107 (56%) to the very high risk group. The treatment was classified as follows: Best supportive care (BSC), low-dose Chemotherapy (LDC), high-dose chemotherapy (HDC), demethylating agents (DMA; either 5-azacytidine or decitabine), and others. Results A best supportive care regimen was chosen in nearly half of the patients (49%). The remaining patients received 1-4 sequential therapies (1: 29%; 2: 11%; 3: 10%; 4: 1%). As the first line therapy, 64 patients (54%) received DMA, 24 (20%) an allo-Tx, 9 (8%) HDC, 5 (4%) LDC, and 16 (14%) were treated with other therapies. The best prognosis was observed in patients eligible for allo-Tx: The median OS in transplanted patients was 924 days as compared to 361 days (p<0.01) in patients not eligible for transplantation. In the latter cohort, patients who received DMA at any course of their disease did not differ from those receiving other therapies: The median OS was 468 days in patients treated with DMA as compared to 325 on those with alternative therapies (p not significant) and the median time to AML-transformation was 580 versus 818 days (p not significant), respectively. However, by classifying patients according to IPSS- and IPSS-R, it became obvious that patients with an IPSS high-risk or an IPSS-R very high risk showed a clear benefit from DMA: In the first group, median OS was 444 days in DMA-treated and 201 days in non-DMA-treated patients (p=0.048), in the latter group, median OS 444 days in the DMA-treated and 203 days in the non-DMA treated cohort (p=0.017). Comparable results were observed regarding AML-free survival: Median time to AML was 580 (DMA) vs. 186 (no DMA) days in IPSS high risk patients (p=0.031) and 580 (DMA) vs. 273 (no DMA) days in the IPSS-R very high risk group (p not significant). Conclusions Patients with MDS, partial or total monosomy 7 and a high risk according to IPSS or a very high risk according to IPSS-R show a pronounced benefit when treated with DMA, regarding overall- as well as AML-free survival. Further results from the ongoing data analysis will be presented in detail. The study was supported by research funding from Celgene. Disclosures: Schanz: Celgene: Research Funding. Braulke:Celgene: Research Funding. Germing:Celgene: Honoraria, Research Funding. Schmitz:Novartis: Research Funding; Celegene: Consultancy, Research Funding, Speakers Bureau. Götze:Celgene: Honoraria. Platzbecker:Celgene: Honoraria, Research Funding. Haase:Celgene: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding.

Abstract Background and Objective: Currently, non-VKA oral anticoagulants (NOAC) are replacing vitamin-K antagonists (VKA) in stroke prevention in atrial fibrillation (SPAF). We evaluated characteristics of SPAF patients that are not switched from VKA to NOACs in daily care. Methods: The prospective Dresden NOAC registry stopped enrolment of dabigatran and rivaroxaban patients on February 28, 2013. At that day, participating sites were asked to enrol all VKA patients seen for regular INR testing who remained on VKA and for whom switching to NOAC was not anticipated. VKA patients were followed for one year. Results: In total, 50 physicians registered both SPAF patients on NOAC-therapy (n=709) and on VKA therapy (n=427; table 1). Compared to the NOAC registry cohort, patients that continued VKA therapy more often were male and less often had a history of TIA/stroke, unstable INR values or a history of bleeding complications compared to the NOAC cohort. The mean duration of VKA pre-treatment was 70.7 months (range 1–432 months). For 328 of the 427 VKA patients (62%), the INR documentation was available for at least 6 months backwards and mean TTR (calculated according to Roosendaal) was 72.2% (SD 19.6). Enrolling sites indicated “stable INR” (95.3%), “costs” (6.3%) and “contraindication for NOAC” (2.3%) as the most common reasons to continue with VKA therapy in these patients. As of June 30th 2014, completed FU correlated to 472.42 patient years. At 12 months-FU (completed in 330 pts.), 311 patients (94.2%) were still taking VKA, 13 patients (3.9%) were switched to other anticoagulants and the remaining 6 patients (1.8%) stopped taking anticoagulants completely. Most common reasons for VKA discontinuation were bleeding complications (7/19; 36.8%) and unstable INR (6/19; 31.6%). Conclusion: NOAC-experienced physicians keep around 40% of anticoagulated SPAF patients on VKA, mostly due to the fact INR is considered to be stable or NOAC to be expensive. The mean TTR of 72% indicates that subjective assessment of INR stability is accurate. Patients with a history of stroke or bleeding complications are more likely to be switched from VKA to NOAC. During the following 12 months, less than 6% of the VKA continuers need to stop VKA treatment, indicating that the subjective assessment of the attending physician identifies patients with acceptable VKA treatment persistence. Table 1: characteristics of 1136 patients selected for VKA continuation (n=427), switch to NOAC (n=291) or new start of NOAC (n=418) in 50 private practises enrolling both VKA and NOAC patients into the registry All patientsn=1136 VKAn=427 Switch VKA to NOACn=291 NOAC newn=418 p-value Male, n (%) 52.82 59.02 50.17 48.33 0.0045 Age, years(median; 25th;75th percentile) 75 (70; 80) 74 (70; 79) 75 (70;81) 76 (70;82) 0.210 Mean BMI ± SD (kg/m2) 28.7 ± 4.9 28.68 ± 4.9 29.06 ± 4.9 28.46 ± 4.9 0.272 Chronic heart failure, (%) 41.29 43.56 43.3 37.56 0.149 Arterial hypertension, (%) 88.56 91.8 84.88 87.8 0.013 Diabetes,(%) 41.73 43.33 43.99 38.52 0.244 Coronary artery disease,(%) 23.06 23.65 22.34 22.97 0.916 Prior stroke or systemic embolism,(%) 13.47 8.9 17.53 15.31 0.001 History of bleeding complications (%) 3.79 0.7 7.56 4.31 <0.001 History of unstable INR 7.39 0.7 26.46 n.a. <0.001 Disclosures Beyer-Westendorf: Bayer: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Boehringer Ingelheim: Honoraria, Research Funding. Werth:Bayer: Honoraria. Köhler:Bayer: Honoraria. Weiss:Boehringer Ingelheim: Honoraria; Bayer: Honoraria.

Abstract Abstract 3752 Background: Long-term treatment with TKIs is of special concern in pediatric patients (pts) with CML as these drugs -beside their specific inhibition of the BCR-ABL oncogene- exert multiple off-target effects. Among these the precise influence on the longitudinal growth and the reproductive endocrine system –being of particular interest in growing organisms– is still not clarified. We therefore investigated in blood serum the growth hormone-related parameter insulin-like growth factor-binding protein 3 (IGFBP3) as well as testosterone (Testo) and inhibin B (InB) in an animal model of juvenile rats and pediatric pts with CML chronically exposed to TKIs. Methods: In 23 pts (13 males; age: 7.8 – 18.9 years, median: 12.8 yrs) with CML in chronic phase being enrolled into the pediatric trial CML-Paed II (ClinicalTrials.gov identifier NCT00445822) blood serum was collected at three months intervals in the morning and sent in for central analysis at the study reference laboratory. Pts were receiving standardized imatinib (IMA) treatment (260–300 mg/sqm) for 3–58 months (median: 18 months). In addition, in an animal model 4 week-old male Wistar rats were cohorted (controls, groups A, B, C; each n=10 animals) and exposed over 10 weeks to either IMA, dasatinib (DASA), or bosutinib (BOSU) at varying concentrations via the drinking water (controls: water only; IMA: A) 1mM, B) 2 mM, C) 2 mM at three days per week [Monday–Wednesday]; DASA and BOSU, respectively: A) 50 μM, B) 100 μM, C) 100 μM at 3 days per week). Blood was collected at prepubertal age (6 weeks old), pubertal age (8 weeks old), and at adult age (14 weeks old), respectively. Serum levels of IGFBP3 (in all pts), Testo, and InB (in males) were measured by commercially available ELISA in humans and rats. Results: IGFBP3 levels were determined in 21 pediatric pts and were found still within the normal, however, uniformly in the very low range (Z-score: −1 to −2) compared to age-matched reference values (p<0.001). In male pts serum levels of Testo (n=13) and InB (n=11) were within normal age-related reference ranges according to Tanner puberty score. No clear pattern of rising or falling Testo or InB levels during TKI treatment could be observed. In rats, compared to controls serum IGFBP3 levels (range: 19–40 ng/ml) were highly significantly lowered (range: 7–16 ng/ml; p-values <0.01 - <0.001) for all TKIs tested, at all concentrations applied, and at all ages when investigated. Also longitudinal bone growth retardation occurred in these animals as described elsewhere (Tauer JT et al. 2011 ASH Abstract #1597; Tauer JT et al. 2012 EHA Abstract #1256). Keeping in mind that the number of animals tested at each age group was rather small, Testo levels under IMA exposure tended to be non-significantly lowered at postpubertal age compared to controls while no significant differences were found under DASA and BOSU exposure. Also for all TKIs tested in rats, InB serum levels did not significantly differ compared to controls. Conclusion: Impairment of longitudinal growth in pediatric pts on TKIs has been described in several reports as well as in animal models (Suttorp M, et al 2012). Besides direct off-target effects on differentiation and metabolic activity of bone resorbing and forming cells (osteoclasts and osteoblasts) involved in bone remodelling, TKI treatment probably results also in lowered growth hormone secretion. Based on these first data from a small cohort of pts it seems reasonable to monitor growth hormone-related parameters like IGFBP3 regularly in pediatric pts with CML. Our data do not confirm a general inhibitory effect on Testo and InB blood levels neither in pts nor in rats. Thus, testicular toxicity due to TKI seems unlikely, however, clinically individual cases with impaired gonadal function and/or late-onset puberty remain to be investigated. Acknowledgment: This investigation was supported by grants DFG SU122–3/1, Peter Escher Foundation (Leipzig), and Foerderkreis Sonnenstrahl e.V. (Dresden). Disclosures: No relevant conflicts of interest to declare.

Abstract Context : Mutations in epigenetic regulators such as TET2 or ASXL1 predict response but do not appear to impact overall survival (OS) in MDS patients (pts) treated with HMA. Somatic mutations are highly frequent in CMML, where ASXL1 confers independent poor prognosis (GFM score; JCO,2013;31:2428). Both azacitidine (AZA) and decitabine (DAC) are active in CMML. The prognostic value of gene mutations in CMML pts treated with HMA has not been analyzed so far. Methods : Retrospective analysis of advanced CMML pts treated with AZA (within EMA label) or DAC (in GFM trials) in GFM centers and Dresden University. Screening for mutations was based on Sanger sequencing (JCO, 2013;31:2428). All statistical analyses were stratified on HMA. Results : Mutation status was available for 79 pts (M/F: 57/22, median age 71y), prior to onset of AZA (n= 46) or DAC (n= 33). Median time from diagnosis to HMA onset was 8 months. At HMA onset, WHO diagnosis was CMML-1, CMML-2 and CMML having progressed to AML in 47%, 39% and 14%, respectively (resp). Pts received a median of 9 cycles for both drugs (range: 1-55). Median follow-up was 50 months. Compared to AZA pts, DAC pts had poorer cytogenetic risk according to CMML Prognostic Scoring System (CPSS, Such Blood 2013: DAC: fav/int/poor in 49/21/30% vs AZA: 78/9/13%, p=0.009), and higher WBC (median 20.6 vs 13.4 G/L p=0.06). The most frequently mutated genes were ASXL1 (47%), SRSF2 (47%), TET2 (40%), NRAS (20%), RUNX1 (19%), KRAS (10%) and CBL (10%). The mutation spectrum was similar in AZA and DAC groups. Overall Response Rate (ORR) was 58% (AZA: 61%, DAC: 55%, p=NS), including CR in 26% and 15%, resp. (p=NS) according to IWG 2006 criteria. In univariate analysis, no single mutation significantly affected ORR, but KRAS-mutated pts tended to have higher ORR than KRAS -wildtype (wt) pts (88 vs 55%, p=0.08). Mutation in either KRAS or NRAS conferred significantly higher CR rate (36%, vs 14% in pts with NRAS/KRAS -wt, p=0.04). Median OS was 27.5 months. In univariate analysis, ASXL1 (HR=2.10, p=0.008), SRSF2 (HR=2.97, p=0.008), RUNX1 (HR=2.40, p=0.01) and to a lesser extent CBL (HR=2.22, p=0.054) mutations conferred poorer OS. TET2 mutations had no prognostic impact. The higher CR rate in pts with KRAS/NRAS mutations did not translate into prolonged OS. There was a significant interaction between ASXL1 and SRSF2 status (p=0.0009). A two-gene classifier could stratify patients with significantly different 3y-OS estimates of 80.8%, 44.1%, and 23.6% in pts with neither, either, or both ASXL1/SRSF2 mutated (Figure; p<0.0001). Other variables associated with worse OS in univariate analysis were age, WBC, peripheral immature myeloid cells (IMC), peripheral blasts, and high risk cytogenetics by CPSS. Splenomegaly, Hb and Plt levels, transfusion dependency (TD) or marrow blast % (hence WHO category) had no impact. CPSS, which includes cytogenetics, WBC, TD and WHO, had thus significant but relatively limited prognostic value, with worse outcome in high vs low risk pts (p=.04), but no difference between low and int-1 or int-2 pts (both p>.2). GFM risk system which includes ASXL1 and WBC, Hb and Plt, also had prognostic value restricted to high vs low risk comparison (p=0.04). In multivariate analysis, the two-gene classifier retained significant prognostic impact (1 mutation: HR=3.5, p=.05; 2 mutations: HR=9.4, p=.001), together with increasing IMC (HR=1.05, p=.04), independently of age, WBC, peripheral blasts and cytogenetic risk. The classifier also had prognostic value independent of CPSS (p=.001). Median OS was 18.4 vs 32.3 months in DAC vs AZA treated pts (p=0.01), but this difference was not significant after adjusting for CPSS cytogenetic risk (p=0.19). Heterogeneity analyses did not identify any significant interaction with the type of HMA independent of cytogenetics or WBC, suggesting no genotype predicted better outcome with one HMA over the other. Conclusion : In this retrospective cohort of CMML pts treated with AZA or DAC, response to HMA could not be predicted by frequently mutated genes, except for a higher CR rate in RAS -mutated pts. Treatment with HMA did not abrogate the poor prognostic value of ASXL1 mutations in CMML. A two-gene classifier based on ASXL1 and SRSF2 could stratify the prognosis of CMML treated with HMA independently of clinical variables. Finally, there was no evidence that genotype should influence the choice of HMA (AZA vs DAC) in CMML. Figure 1. Figure 1. Disclosures Off Label Use: Decitabine off label to treat CMML. Platzbecker:GlaxoSmithKline: Honoraria, Research Funding; Amgen, Inc.: Honoraria; Celgene: Honoraria; Novartis: Honoraria. Park:Hospira: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding. Vey:Celgene: Honoraria; Roche: Honoraria; Janssen: Honoraria. De Botton:Agios Pharmaceuticals: Research Funding. Fenaux:JANSSEN: Honoraria, Research Funding; CELGENE: Honoraria, Research Funding; AMGEN: Honoraria, Research Funding; NOVARTIS: Honoraria, Research Funding. Itzykson:Oncoethix: Research Funding.

Abstract Introduction: Total (-7) or partial (7q-) monosomy 7 is the second frequent abnormality in MDS, occurring in around 12% of MDS/AML and up to 40% of therapy-associated MDS/AML. The present study was designed to analyze clinical features, prognosis and response to different therapeutic strategies in patients with -7 or del(7q) in a multicentric, retrospective cohort study. Patients and Methods: 471 patients with MDS/AML following MDS and monosomy 7 were registered and retrospectively analyzed. The median observation time was 3.6 years. Inclusion criteria were defined as follows: Morphologic diagnosis of MDS/AML following MDS, bone marrow blast count <=30% and presence of -7 or 7q- proved by chromosome banding analysis (CBA) or fluorescence in situ-hybridization (FISH). The data was coalesced from 8 centers in London (n=140; 29.7%), Duesseldorf, (n=120; 25.5%%), Goettingen (n=118; 25.1%), Cologne (n=38; 8.1%), Freiburg (n=29; 6.2%), Munich (n=13; 2.8%), Dresden (n=10; 2.1%) and Mannheim (n=3; 0.6%). The median age in the study cohort was 66 years, 63% of patients were males. MDS/AML was therapy-associated in 53 (11%). According to IPSS-R, 9 (1.9%) were assigned to the low risk group, 39 (8.3%) to the intermediate group, 81 (17.2%) to the high-risk group and 133 (28.2%) to the very high risk group. The treatment was classified as follows: Best supportive care (BSC), low-dose Chemotherapy (LDC), high-dose chemotherapy (HDC), hypomethylating agents (HMA; either 5-azacytidine or decitabine), and others (e.g. valproic acid, steroids, lenalidomide or thalidomide). Survival analyses were performed regarding overall- (OS) as well as AML-free survival (AFS) using the Kaplan-Meier method. Results: 147 patients (31.2%) showed 7q-, 313 (66.5%) -7 and 11 (2.3) patients showed both abnormalities at the first cytogenetic examination. The abnormality was detected by CBA±FISH in 440 (93.4%) and by FISH only in 31 (6.6%). In the latter cases, the CBA was either unsuccessful or showed a normal karyotype. In 182 (38.6%) patients, -7/del7q was detected as a single abnormality, 77 (16.3%) showed two abnormalities and 184 (39.1%) showed a complex karyotype involving -7/7q-. As previously described (Schanz et al., 2012), untreated patients with an isolated 7q- as compared to an isolated -7 show a better prognosis regarding OS (median: 4.0 vs. 0.7 years; p<0.01) as well as AFS (median not reached vs. 2.3 years; p=0.062). Median hemoglobin level in the study cohort was 9.3 g/dl, ANC 0.98*103/μl, platelet count 73*103/μl and the median number of bone marrow blasts was 8%. Regarding the treatment, a best supportive care regimen was chosen in 195 (41%) patients. The remaining 276 (58.6) patients received 1-5 sequential therapies (one therapy: 31.6%; more than 1 therapy: 27.0%). 81 patients received an allogeneic bone marrow transplantation (ATX). Within the group of patients treated with HMA at any time of their disease (n=167), 147 (31.2%) received 5-Azacytidine, 8 (1.7%) Decitabine and 12 (2.5%) patients were treated with both drugs. As the first line therapy, 122 patients (25.9%) received HMA, 50 (10.6%) HDC, 28 (5.9%) ATX, 28 (5.9%) 11 (2.3%) LDC, and 28 (5.9%) were treated with other therapies. Patients eligible for ATX showed a significantly better prognosis as compared to any other therapy strategy: The median OS in was 2.1 years as compared to 1.1 years in non-transplanted patients (p<0.01). In patients not eligible for ATX, treatment with HMA at any course of their disease as compared to a BSC strategy was associated with a better OS (1.4 vs. 0.8 years, p=0.014). By comparing HMA to any other therapy, the OS did not differ significantly (1.4 years in HMA vs. 1.1 years in any other, p n.s.). In patients classified as very high risk according to IPSS-R, the median OS was significantly prolonged in patients receiving HMA as compared to BSC (1.1 vs. 0.6 years, p<0.01). This was also observed for the risk of AML-transformation in this subgroup of patients: The median time to AML was 1.8 years in HMA-treated patients versus 0.6 years in BSC (p=0.012). Conclusions: To our knowledge, the study describes the largest patient cohort with MDS/AML and monosomy 7 published to date. Further data regarding the clinical characteristics of this subgroup of patients and the treatment regimes applied will be presented in detail. The study was supported by research funding from Celgene Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Schanz: Celgene: Honoraria, Research Funding, Travel grants: Celgene, Novartis, Lilly Other. Götze:Celgene Corp, Novartis Pharma: Honoraria. Nolte:Celgene, Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Travel grants Other.

Abstract Purpose Counselling of patients with AML about allogeneic hematopoietic stem cell transplantation (alloHSCT) is still an ambitious task in the light of the potential curative perspective after alloHSCT, poor outcomes after non-transplant approaches but a high risk of transplant-associated complications and still a significant risk of relapse even after HSCT. Several scores have been developed to predict outcome after HSCT, such as the HCT-CI and the Pre-transplant Assessment of Mortality (PAM) score. The PAM score has been revised recently, thereby acknowledging the shift to more frequently used reduced intensity conditioning. This score utilizes information on pts.age, donor type, disease risk, theserostatus for the CMV of pts.and donor, and the forcedexspiratory volume in the 1 second (FEV1). The aim of this study was to analyze the predictive power of the PAM score in an independent, large cohort of AML pts.who receivedalloHSCT within the last 12 years. Patients and Methods We selected all adult AMLpts.whoreceived the firstalloHSCTat the University Hospital of Dresden, a tertiary care hospital with a large transplant program, from January, 1, 2003 to July, 1, 2015.Pts.withhaplo-identical donors or after cord-blood transplantation were excluded. All patients gave their informed consent on analysing data. The PAM score was calculated as published (Au et al., BBMT 2015) and stratified into 4 groups: scores <17,scores17 to <24, scores 24 through 30, and scores >30. Overall survival (OS), event-free survival (EFS), cumulative incidence of relapse (CIR) and non-relapse-mortality (NRM) after alloHSCTwereanalyzed according to several factors known to impact outcome using the log-rank test for univariate comparison. Age, AML type (de novo vs. sAMLvs. t-MN), sex match (female donor/male recipient vs. all other), CMV match (negative/negative vs. all other), donor type (sibling vs. matched unrelated vs. mismatched unrelated), ELN risk classification, type of conditioning (RIC vs. MAC), disease stage (CR1 vs. primary induction failure vs. >= first relapse) and the PAM score as a continuous variable were selected a priori for multivariate Cox regression analyses. Results Overall, 544 pts.metthe inclusion criteria and were analyzed,the median age was 57 years (range, 18 to 76). Two-hundred-three pts.(37%) were treated with standard myeloablative conditioning (MAC) regimens while the remaining pts. received reduced intensity conditioning (RIC). Donors were siblings in 120 (22%), matched unrelated in 295 (54%) and mismatched unrelated donors in 129 (24%) pts. With a median follow up of 47 months (range, 1 to 161), the estimated OS for the whole cohort at five years was 43%, with a CIR of 30% and a NRM of 31% up to that time-point. The probability for OS at five years for pts.in PAM score group 0, 1, 2, and 3 was 65%, 50%, 33%, 22%, respectively (log-rank test, p= <.001). Both the CIR and NRM increased with increasing PAM scores (gray-tests, p= .005 and p= <.001, respectively). Notably, the PAM score contributed significantly to the prediction of OS even when added to a multivariate regression model which contained the single components of the score. In the final multivariate model, age (HR 1.02 per year, p= .004), disease stage (primary induction failure versus CR1, HR 1.5, p= .03), and the PAM score (HR 1.04, p= .03) had a significant impact on OS. Conclusion We validated the revised PAM for the prediction of OS after HLA-compatiblealloHSCTin a large, well characterised cohort of AMLpts.treatedat a large German transplantcenter. To the best of our knowledge, this is the first external validation of the revised PAM score. OS prediction based on this tool will be useful for counselling of futurepts.withAML. Figure OS after HSCT according to the PAM score Figure. OS after HSCT according to the PAM score Disclosures Middeke: Sanofi: Honoraria. Thiede:AgenDix: Employment, Other: Ownership. Schetelig:Sanofi: Honoraria.

Abstract Background Older admitted patients are at risk of deconditioning related to immobility. “Fit to Sit” is a simple change in the Emergency Department (ED) culture and attitude, promoting independence, maximizing well-being and improving health outcomes. We aim to describe the prevalence of patients deemed “Fit to Sit” who were in hospital gowns and lying on trolleys in our ED prior to the commencement of the “Fit to Sit” pilot. Methods An observational study was conducted prospectively, over five working days, to determine the proportion of patients present who were dressed and sitting out on a chair, opposed to wearing pyjamas (PJs) and lying on a trolley. Nursing staff familiar with each patient were asked whether or not the patient was fit to sit out in a chair. Statistical analysis was conducted with Microsoft Excel using the chi squared test to calculate differences between the two groups. Results Data was collected on 147 patients, median age 66 years (IQR 47-74). 82% were on a trolley and 18% in a chair. 33% were in their clothes, the remaining 67% were in PJs or hospital gowns. 45% of those deemed “Fit to Sit” were on a trolley. Patients 65 and older were more likely to be wearing PJs (p= 0.03), but not more likely to be on a trolley (p= 0.23). Patients in ED for greater than 12 hours were also more likely to be in PJs (p= 0.001) and on a trolley (p= 0.057). Conclusion Our study suggests that a significant proportion of ED patients are lying on trolleys despite being deemed to be “Fit to Sit”. Introduction of an ED “Fit to Sit” programme may alleviate deconditioning and promote patient independence.

Abstract Abstract 3816 Background Conventional chromosome banding (CCB) analyses of bone marrow (bm) metaphases represent the gold standard of cytogenetic diagnostics in myelodysplastic syndromes (MDS), but they are not suitable for frequent follow-up analyses. Most aberrations can also be detected by fluorescence in situ hybridisation (FISH), and they are provable in CD34+ cells from peripheral blood (pb). In our prospective multicenter German diagnostic study “Screening and genetic monitoring of patients with MDS under different treatment modalities by cytogenetic analyses of circulating CD34+cells” (ClinicalTrails.gov NCT01355913) we followed MDS pts by sequential FISH analyses. Methods CD34+ pb cells were enriched by immunomagnetic cell sorting (MACS®) and analysed by FISH using a “Superpanel” (D7/CEP7, EGR1, CEP8, CEP XY, D20, TP53, IGH/BCL2, TEL/AML1, RB1, MLL, 1p36/1q25, CSF1R, all Abbott® Products) at initial screening, every 12 months during follow-up and in case of suspected disease progression and a “Standardpanel” (EGR1, D7/CEP7, CEP8, TP53, D20, TEL/AML1, CEP XY, plus -if necessary- another informative probe) every 2 months in the 1st and every 3 months in the 2nd and 3rd year. If bm aspirate was available, additional CCB and FISH analysis of CD34+ and native bm cells were performed. Cut-off values for each FISH probe were evaluated in our lab. Cytogenetics, bm morphology, clinical course and therapies were documented in a database. All pts gave their written informed consent. The study was approved by all local ethic committees. Results After 3 years of study time, 361 patients (25 AZALE (University of Dresden), 110 LEMON5 (University of Duesseldorf), 226 CD34+FISH) have been included in the study, resulting in a total number of 19,516 FISH analyses: Median age, gender distribution and MDS subtypes were typical for the disease, median follow-up at the time of analysis was 8.2 (1–36) months. Chromosomal aberrations could be detected by FISH of CD34+ pb cells in 71.5% of pts (55% of CD34+FISH-cohort, 99% of LEMON5-trial pts, 100% of AZALE-trial pts). FISH and CCB were highly correlated: p<0.01 for CD34+ pb FISH vs CCB and p<0.01 for CD34+ bm vs CCB. The clone sizes were significantly larger in CD34+ cells compared to native pb (p<0.01). Discussion Our interim results demonstrate that FISH analysis of circulating CD34+ pb cells provides relevant cytogenetic informations. It is a reliable novel method for screening and cytogenetic monitoring of MDS pts during the course of disease and under different therapies, and helps in cases where a bm biopsy is not possible or not successful. Disclosures: Braulke: Celgene: This study was supported by Celgene. Other. Götze:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Bug:Celgene: Honoraria, travel support, advisory board Other; Novartis: Honoraria, travel support, advisory board, travel support, advisory board Other; Boehringer Ingelheim: Honoraria, travel support, advisory board, travel support, advisory board Other. Schafhausen:Novartis: Honoraria, travel support Other; BMS: Honoraria, travel support, travel support Other; Roche: Honoraria, travel support, travel support Other; Celgene: Honoraria, travel support, travel support Other; Alexion: Honoraria, travel support Other. Haase:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Abstract Abstract 6 Background Simultaneous ATRA and chemotherapy (CHT) is the current gold standard for newly diagnosed APL resulting in ∼80% cure rates, while arsenic trioxide (ATO) is the treatment of choice for relapsed patients. ATO in variable combinations including ± ATRA ± CHT has also been tested as front-line therapy yielding encouraging results in several pilot studies as well as in two phase III studies conducted in China and the US. So far, no randomised studies have compared front-line CHT-free ATO+ATRA combination against the standard ATRA+CHT approach. Patients and Methods The phase III, randomised, prospective APL0406 trial was started in October 2007 by the Italian GIMEMA group and joined in November 2008 by the German SAL and AMLSG multicenter groups. Eligible patients were adults aged 18-<71 years with newly diagnosed, genetically confirmed, non-high-risk (WBC≤10×109/L) APL. Patients were randomized to receive the ATO+ATRA combination originally reported by the MD Anderson group (Estey et al. Blood 2006, arm A), or the Italian AIDA2000 risk-adapted protocol for non high-risk disease (arm B). Patients in arm A received ATO 0.15/kg plus ATRA 45 mg/m2 daily until CR, then ATO 5 days/week, 4 weeks on 4 weeks off, for a total of 4 courses and ATRA 2 weeks on and 2 weeks off for a total of 7 courses. Patients in arm B received the standard AIDA (ATRA+Idarubicin) induction followed by 3 cycles of anthracycline-based plus ATRA consolidation and low dose CHT and ATRA for maintenance as reported (Lo-Coco et al., Blood 2011). The primary study objective was EFS at 2 years. The study was designed to show that the rate of patients alive event-free at two years in the experimental treatment arm is at least 80%. Secondary objectives included OS, DFS, CIR rates, molecular response and toxicity profile. Results From October 2007 to September 2010, the required sample size of 162 enrolled patients was completed. Median age was 45.3 years (18.7–70.2 years) and median WBC 1.50 × 109/L. As to the Sanz's risk score, 61.8% and 38.2% of patients were in the intermediate- and low-risk categories, respectively. The two treatment arms were well balanced for main baseline characteristics including age, sex, median WBC and Sanz's score. Eight patients were not evaluable for induction due to ineligibility or protocol violation. Of 154 patients evaluable for response to induction, CR was achieved in 150 (97.4%): 75/75 (100%) in arm A vs 75/79 (95%) in arm B (P=0.12). After a median follow-up of 31 months (range 0.07–50.4) the 2 year EFS (primary objective) was 97% (C.I.95%: 93.1–100) and 86.7% (C.I.95%: 80.3–93.6) in arms A and B respectively (P=0.03). There were 1 death in CR and 2 relapses in arm A, and 7 deaths (4 in induction, 3 in CR) and 4 relapses in arm B. As to secondary objectives, OS, DFS, and CIR rates were 98.7% vs. 91.1% (P=0.03), 97% vs. 91.6% (P=0.19) and 1.6% vs. 4.3% (P=0.41) in arm A and B, respectively. Fever episodes, prolonged (>15 d) grade ≥ 3 neutropenia and thrombocytopenia were significantly more frequent in patients in arm B as compared to those in arm A (P <.001 for all comparisons). Other side effects including differentiation syndrome and increase of liver enzymes were recorded with similar frequency in the two study arms. Two patients in arm A had QTc prolongation requiring ATO discontinuation with final withdrawal in one case. PCR analysis of PML/RARA (sensitivity 10−4) was centrally performed in Rome (F. Lo-Coco) and Dresden (C. Thiede) and showed molecular CR in 141/142 (99%) of evaluable patients after completion of 3rd consolidation. One patient in arm B who tested PCR-positive at this time point was considered resistant and taken off protocol as per study design. Conclusions For patients with newly diagnosed non-high-risk APL, as compared to the standard AIDA regimen, the front-line CHT-free ATO+ATRA combination is at least not inferior for 2 year EFS. Disclosures: Lo-Coco: Boehringer Ingelheim: Membership on an entity's Board of Directors or advisory committees; Cephalon: Speakers Bureau. Off Label Use: Arsenic Trioxide (ATO) is currently approved for therapy of relapsed APL in the US and Europe. In this study the role of ATO in front-line therapy of APL is explored. Fiedler:Pfizer Inc.: Consultancy, Research Funding; Novartis: Consultancy, Research Funding. Breccia:Celgene: Honoraria; Novartis: Honoraria; BMS: Honoraria. Platzbecker:GlaxoSmithKline: Consultancy; Celgene: Consultancy; Novartis: Consultancy; Amgen: Consultancy.

Abstract Introduction: Myelodysplastic syndromes (MDS) are clonal stem cell disorders associated with bone marrow failure. Allogeneic stem cell transplantation (alloSCT) is currently the only curative therapy option for patients with MDS. However, on the one hand, most MDS patients are older than 60 years and non-relapse mortality (NRM) remains a significant problem. Therefore, only patients with higher risk MDS according to IPSS (intermediate-2 or higher) appear to profit from alloSCT. On the other hand, higher risk MDS patients have increased relapse rates following alloSCT. In order to optimize the application of alloSCT in this disease, both relapse and NRM rates need to be reduced. We have recently provided evidence that weight loss and minor metabolic changes prior to alloSCT were able to predict relapse and death of acute myeloid leukemia patients using data from two independent patient cohorts This retrospective study investigated the influence of pre-transplant weight loss on clinical outcome of MDS patients after alloSCT in three independent cohorts. Patients and methods: A total of 110 patients (59% male) with a median age of 53 years were included into the analysis. Patients have been diagnosed with MDS according to WHO criteria and received an alloSCT between 2000 and 2012 in three different German referral centers (Heidelberg, Dresden and Berlin). Patient data was retrospectively collected by medical chart review according to the declaration of Helsinki and with approval of the local Ethics committees. Weight data were raised from medical records by three independent researchers in three independent institutions. Weight loss (expressed in percent) was calculated on the basis of recorded weight data at the time of alloSCT and the maximum weight in the time period of 3-6 months prior to alloSCT. The MDS WHO subtype was RA(RS)/RCMD in 31 patients (28%), RAEB1 in 30 patients (27%) and RAEB2 in 49 patients (45%). According to IPSS 31%, 47% and 22% of the patients were in the risk groups intermediate-1, intermediate-2 and high, respectively. The majority of the patients (n=71, 65%) was previously untreated. Twenty-four patients (22%) and 14 patients (13%) received hypomethylating agents and classic chemotherapy prior to alloSCT, respectively. Thirty-one patients (28%) received transplants from related donors (RD), 58 patients (53%) from matched unrelated donors (MUD) and 21 (19%) from mismatched unrelated donors (MMUD). Ninety-three patients (85%) received reduced intensity conditioning (RIC) and 17 patients (15%) received standard myeloablative conditioning (MAC). Survival times were measured from date of alloSCT. Overall survival (OS), relapse-free survival (RFS), NRM and were calculated from date of alloSCT to the appropriate endpoint. Cox regression analysis was applied for OS, NRM and RFS. Relapse and NRM were considered as competing risks. As confounding prognostic factors we included weight loss (continuous), IPSS score, pretreatment, donor type, sex mismatch with the donor and type of conditioning. Results: Median follow-up time was 36 months. For both endpoints OS and NRM multivariate analysis revealed a significant interaction between weight loss and donor type (p<0.01). In Cox regression analysis with the endpoint RFS only weight loss (p=0.05) was associated with significantly shorter RFS. The prognostic effect of pre-transplant weight loss on OS, NRM and RFS and the increasing hazard ratios (HR) with corresponding confidence intervals (CI) for different percentages of weight loss are given in Table 1 (multivariate Cox regression). In a mixed effect model with weight loss as outcome age, recipient sex and pretreatment had no significant impact on weight loss. However, there was a trend towards increased weight loss in patients with high risk MDS according to IPSS (p=0.07). Conclusion: Our retrospective study suggests that in MDS patients pre-transplant weight loss is associated with both higher disease recurrence and higher NRM resulting in survival disadvantage after alloSCT. Prospective studies addressing pre-transplant nutritional interventions in order to improve the outcome of MDS patients are highly warranted. Table 1. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Abstract Introduction: After an allogeneic stem cell transplantation (SCT), analysis of donor chimerism (DC) is routinely used to monitor engraftment. In patients with myeloid malignancies, loss of a complete donor chimerism (CC) may indicate graft failure, but more often imminent leukemic relapse. Especially in patients without a valid marker for minimal residual disease (MRD), chimerism analysis may prompt reduction of immunosuppression or therapeutic interventions such as donor lymphocyte infusions (DLI) or hypomethylating agents (HMA). We retrospectively analyzed DC data and outcomes of 255 consecutive patients (pts) transplanted for an acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) at our center. Aims of our study were to evaluate the impact of (i) a falling DC, (ii) the first chimerism-guided intervention, and (iii) the application of DLI on survival and incidence of acute and chronic (a/c) GvHD. Patients and Methods: 255 pts that received a first SCT between 2005 and 2016 were monitored regularly (approx. every two weeks from day +14 to +100, then monthly) for DC using a validated, CE-labeled multiplex-STR PCR at a single laboratory (AgenDix GmbH, Dresden, Germany). CC was defined as ≥99% and mixed chimerism (MC) as <99% donor cells. Overall survival (OS), GVHD-free, relapse-free survival (GFRS) and the cumulative incidence (CI) of GVHD was analyzed for the whole cohort, OS and CI GVHD were analyzed for pts with MC and pts that received DLI with a prophylactic/preemptive (pDLI) vs. therapeutic (tDLI) indication. 245 pts (median age 53 years (range 19-73), 136 male) with AML (n=222) or MDS (n=23) achieved a CC within 60 days post SCT and were eligible for our analysis, 10 pts were excluded due to refractory disease (n=9) or early death (n=1). 101 out of 222 AML pts (45%) had intermediate (int)-2 or adverse cytogenetics according to ELN guidelines, and 10 out of 23 MDS pts (43%) had IPSS int-2 or high risk. 121 pts (49%) were transplanted in first complete remission (CR), 107 (44%) with active disease. For SCT, 96 pts (39%) had received myeloablative (MAC) and 149 (61%) reduced intensity conditioning regimens (RIC). Donors were HLA-matched siblings (MRD, n= 60) or unrelated donors (MUD, n=149), mismatched related (MMRD, n= 1) or unrelated donors (MMUD, n=27), or haploidentical family members (n=8). Results: A MC was detected in 95 pts (39%) at a median of 104 (range, 28-1764) days post SCT, of whom 18 pts (32%) had aGVHD G2-4. Pts with MC had received RIC significantly more often compared to pts with continued CC (69% vs 55%, p=0.046), the two groups did not differ regarding high risk cytogenetics/IPSS and remission status at SCT. MC prompted reduction of immunosuppressive therapy (IST, n=35), DLI (n=7), HMA (n=16), DLI+HMA (n=7), chemotherapy and/or 2ndSCT (n=7), small molecules (n=10) or best supportive care (BSC, n=13) as deemed appropriate by the treating physician. Median OS and GFRS were significantly better for pts with CC (OS not reached; GFRS 46 months (mths)) compared to pts with MC (OS 15.7 mths; Hazard ratio (HR) 0.25, 95%-CI 0.17-0.37, p<0.001, GFRS 3.7 mths; HR 0.39, 95%-CI 0.26-0.58, p<0.001, figures 1,2). 3-year survival was 75% for the CC group vs 31.7% for the MC group. For the 95 pts with MC, median OS was 27.4 and 35.8 mths following IST reduction or DLI+HMA, respectively, and 12, 8.8, 5.1 and 1.2 mths for pts treated with chemo/2ndHSCT, HMA, small molecules or BSC. Treatment of MC induced aGVHD G2-4 in only 2 additional pts (G3-4: n=1). CI of cGVHD requiring systemic IST was 27% at 1-year for all pts with MC compared to 13.9% for pts in the CC group. In the whole cohort, 46 pts (19%) received a median of 2 DLIs (median dose 0.5x106CD3+cells/kg). PDLIs were administered to 33 pts (72%) and tDLIs to 13 pts with relapsed disease (28%). The pDLI group had a 3-year survival of 82.9% and did not reach median OS, compared to 24.6% 3-year survival and 22 mths median OS in the tDLI group. Median GRFS was 91.4 vs 6.6 mths for the pDLI and tDLI group, respectively. No pt developed aGVHD G2-4 after DLI administration, 1 pt (8%) in the tDLI and 4 pts (12%) in the pDLI group developed cGVHD requiring systemic IST. Conclusion Occurrence of MC seems predictive of an inferior outcome, but early intervention such as careful reduction of IST if feasible or administration of DLI with or without HMA may effectively prolong OS and GRFS. Administration of pDLI after discontinuation of IST starting with low doses is safe and results in low rates of cGvHD. Disclosures Lang: Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Research Funding. Toenges:Bayer: Research Funding. Schetelig:Sanofi: Consultancy, Research Funding; Roche: Honoraria; Abbvie: Honoraria; Janssen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Honoraria, Research Funding. Serve:Bayer: Research Funding. Thiede:AgenDix: Other: Ownership; Novartis: Honoraria, Research Funding. Bug:Astellas Pharma: Other: Travel Grant; Novartis Pharma: Honoraria, Research Funding; Neovii: Other: Travel Grant; Jazz Pharmaceuticals: Other: Travel Grant; Janssen: Other: Travel Grant; Celgene: Honoraria; Amgen: Honoraria.

Abstract Context : Response to treatment in CMML is difficult to evaluate. Most clinical trials so far included CMML patients (pts) together with MDS pts and assessed response with MDS IWG 2006 criteria (Cheson, Blood 2006), which poorly predict overall survival (OS) with HMA. Recently, an International Consortium has proposed MDS/MPN response criteria (IC-MDS/MPN), considering reduction in blasts (marrow response), but also correction of cytopenias or of myeloproliferation (clinical benefit; Savona, Blood 2015). These new criteria have never been compared to IWG 2006 and their prognostic relevance is unknown. Methods : We analyzed a retrospective cohort of advanced CMML pts treated ith AZA (within EMA label) or DAC (in GFM trials) in GFM centers and Dresden. All analyses were stratified on HMA. Agreement between criteria was assessed by Cohen's kappa, a measure of reproducibility ranging from 0 (no concordance) to 1 (perfect concordance). Survival analysis was censored at transplant and Cox models were performed by Mantel-Byar method, considering achievement of response at first assessment as a time-dependent variable. Results : The cohort included 80 pts (M/F: 56/24) with a median age of 70y (range: 41-91). HMA was AZA and DAC in 49 and 31 pts, respectively (resp.). Median interval between diagnosis and onset of HMA was 4.3 months. At onset of HMA, WHO diagnosis was CMML-1 and CMML-2 in 56% and 44%, resp. Splenomegaly was present in 40%. Median WBC, Hb and Plt counts were 14.7 10^9/L, 9.6 g/dL and 103 10^9/L, resp.; 48% pts were RBC-TD. Cytogenetic risk according to CPSS (Such, Haematologica 2011) was fav/int/low in 63/13/24% resp. CPSS risk category (Such, Blood 2013) was low/int-1/int-2/high in 10/21/54/15%, resp. ASXL1 was mutated in 43% of pts and GFM risk (Itzykson, JCO 2013) was fav/int/low in 29/36/35%, resp. DAC and AZA were administered at standard regimens (20 mg/m2/d x5d/28d; 75 mg/m2/d x7d/28d), for a median of 9 and 7 cycles in DAC and AZA pts, resp. (p=.96). AZA regimen was intensified or reduced in 2 and 5 pts, resp. HY was administered concomitantly for the first cycles in 11%. Median follow-up was 59 months, during which 12 pts were transplanted. Median OS and AML-free survival (AMLFS) were 25.7 and 21.0 months, resp. Initial response was assessed after a median of 4 cycles (AZA/DAC: 5/3, p<.0001); overall response rate (ORR) according to IWG 2006 was 45%, including 14% CR, 11% marrow CR (mCR), no PR, 20% stable disease with HI, while the remaining 55% had stable (SD: 21%) or progressive (PD: 34%), disease. ORR according to CI-MDS/MPN was 65%, including CR in 6%, optimal (OMR) and partial (PMR) marrow response in 44 and 4% resp. and clinical benefit (CB) in 11%. Best IWG 2006 and IC-MDS/MPN response were achieved after a median of 5 (range: 1-18) cycles, without difference between HMA. Improvement from initial assessment to best response was noted in 12 and 11 pts with IWG 2006 and IC-MDS/MPN criteria, resp., leading to ORR of 56% (CR 21%, mCR 11%, HI 24%) and 71% (CR 12%, OMR 28%, PMR 1%, CB 30%), resp. PR was not observed with either set of criteria. A moderate agreement was found between these two sets of criteria at initial evaluation (agreement in 78% cases, Cohen's kappa: .56), with better agreement for best response (85% cases, kappa: .68). Responses according to IC-MDS/MPN criteria were more prolonged than those defined by IWG 2006 (median duration: 19.3 vs 10.8 months, resp. p=.0004), possibly because the former, but not the latter, require additional criteria in addition to blast increase to define progression. CPSS risk category did not predict IWG 2006 or IC-MDS/MPN response (p>0.2), but higher GFM risk tended to predict lower rates of IWG 2006 (p=.06) or IC-MDS/MPN (p=.15) response. Achievement of IWG 2006 (HR=.45, p=.011) or of IC-MDS/MPN (HR= .33, p=.001) response both lead to prolonged OS. Further dissecting IC-MDS/MPN response subtypes, a significant OS benefit was found in patients achieving OMR or CR (p=.003, Figure), but not in those achieving only CB (p=.31) or partial marrow response (p=.76). Similar findings were made for AMLFS. Conclusion : Compared to IWG 2006, IC-MDS/MPN responses to HMA in CMML are more frequent and more prolonged. CPSS and GFM risk scores do not predict response. Optimal marrow response (OMR, reduction of bone marrow blast < 5%) at first assessment predicts longer OS and AML-free survival and could be a relevant short-term endpoint for future clinical trials of HMA in CMML. Figure 1. Figure 1. Disclosures Off Label Use: Decitabine (use off label in CMML). Platzbecker:AMGEN: Honoraria; NOVARTIS: Honoraria; CELGENE: Honoraria. Park:Hospira: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding. Vey:Celgene: Honoraria; Roche: Honoraria; Janssen: Honoraria. De Botton:Agios Pharmaceuticals: Research Funding. Fenaux:NOVARTIS: Honoraria, Research Funding; AMGEN: Honoraria, Research Funding; JANSSEN: Honoraria, Research Funding; CELGENE: Honoraria, Research Funding. Itzykson:Oncoethix: Research Funding.

Abstract Introduction: A series of studies suggest that harnessing natural killer (NK) cell reactivity by killer cell immunoglobulin-like receptor (KIR) genotype based unrelated donor selection could further improve outcome after allogeneic hematopoietic cell transplantation (alloHCT). A Receptor-Ligand model has been proposed for donor selection which aims at augmenting NK cell activation while minimizing inhibition. Information on education of KIR2DS1-positive NK cells (Venstrom et al, NEJM 2012) and the predicted Receptor-Ligand interaction of KIR3DL1-positive NK cells is utilized for this algorithm. By combining this information donors can be classified as KIR-advantageous or disadvantageous. Patients with donors, characterized by activating KIR2DS1 and weak/non-inhibiting KIR3DL1, experienced less relapse and improved survival compared to patients with donors, characterized by lacking an activating KIR2DS1 but presence of strong-inhibiting KIR3DL1. This study aimed at validating this predictor in an independent cohort of patients. Methods: Donor samples were retrieved from the Collaborative Biobank (Dresden, Germany) and mapped to patient outcome data extracted from the German Registry for Stem Cell transplantation. KIR typing was performed using a high resolution amplicon-based next generation sequencing method. KIR typing at the allele level was based on sequencing of exons 3, 4, 5, 7, 8, and 9. The patient population was restricted to patients with AML or MDS. Donor and patient mapping was cross-checked by HLA-typing of the donor sample. The impact of the predictor on overall survival was tested in a Cox regression model adjusted for patient age, a modified disease risk index, performance status, donor age, HLA-match, sex match, CMV match, conditioning intensity, type of T-cell depletion and graft type. Results: Clinical data from 2314 patients were analyzed. The median age at alloHCT was 59.4 years (range, 18.1 to 79.6 years). The indication for alloHCT was AML for 80% of patients and MDS for 20% of patients. Disease risk was assessed as low, intermediate, high or very high in 1%, 52%, 42%, and 5%, respectively. Patient and donor were 10/10 matched in 78% of pairs, whereas a one locus mismatch was reported for 21% of pairs. Myeloablative, reduced-intensity and non-myeloablative conditioning regimens were used in 29%, 67%, and 4% of patients, respectively. ATG was administered in 77% and alemtuzumab in 3% of patients. Twenty percent of patients received no T-cell depletion. In total, 535 patients experienced relapse and 945 patients died. This number of events translated into a power of the confirmatory analysis for the predictor of KIR2DS1 and KIR3DL1 of 67%. Two-year overall and event-free survival for the whole cohort was 51% (95%-CI 48% to 53%) and 44% (95%-CI 42% to 47%) and the 2-year incidence of relapse and non-relapse mortality was 28% (95%-CI 26% to 30%) for both endpoints. In univariate analysis, overall survival (54% versus 56%) and the cumulative incidence of relapse of patients with a KIR-advantageous donor were comparable to patients with KIR-disadvantageous donors. The adjusted hazard ratio from the multivariable Cox regression model for the comparison of patients with KIR-advantageous versus KIR-disadvantageous donors was 0.99 (Wald-test, p=0.95) for overall survival and 1.12 (Wald-test, p=0.41) for relapse incidence. When evaluated separately, the two components of the predictor (degree of inhibition by KIR3DL1 & presence of activating KIR2DS1) did not have an impact on overall survival or the incidence of relapse (see Figure). Also, evaluation of the combined predictor in subsets of patients by disease, type of T-cell depletion and HLA-compatibility did not allow prediction of these outcomes. Conclusions: Relapse incidence and overall survival after unrelated donor alloHCT could not be predicted using information on activating KIR2DS1 and inhibiting KIR3DL1 donor genes in an independent cohort of predominantly Caucasian patients. The predictor had been developed in a cohort of patients with AML who were younger and predominantly had received myeloablative conditioning based on total-body irradiation, ATG was administered less often, but donors often were only partially HLA-compatible. The different outcome in the current analysis thus points at potential interactions between NK-cell mediated allo-reactivity and procedural variations of alloHCT. Figure Figure. Disclosures Schetelig: Sanofi: Consultancy, Research Funding; Janssen: Consultancy, Honoraria; Roche: Honoraria; Abbvie: Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Honoraria, Research Funding. Stelljes:Novartis: Honoraria; MSD: Consultancy; Pfizer: Consultancy, Honoraria, Research Funding; JAZZ: Honoraria; Amgen: Honoraria. Ayuk:Therakos (Mallinckrodt): Honoraria; Novartis: Honoraria; Celgene: Consultancy; Gilead: Consultancy. Bethge:Neovii GmbH: Honoraria, Research Funding; Miltenyi Biotec GmbH: Consultancy, Honoraria, Research Funding. Bug:Neovii: Other: Travel Grant; Novartis Pharma: Honoraria, Research Funding; Janssen: Other: Travel Grant; Celgene: Honoraria; Amgen: Honoraria; Astellas Pharma: Other: Travel Grant; Jazz Pharmaceuticals: Other: Travel Grant. Kobbe:Roche: Honoraria, Research Funding; Celgene: Honoraria, Other: Travel Support, Research Funding; Amgen: Honoraria, Research Funding. Beelen:Medac: Consultancy, Other: Travel Support. Fleischhauer:GENDX: Research Funding.

Purpose: To assess the changes in ocular high order aberrations after collagen cross linking for keratoconus. Patients and Methods: This study included 30 eyes with confirmed KCN. Baseline evaluation focused on: UDVA and BSCVA using logMAR notation, MRSE, corneal topography using Orbscan IIZ and wave-front aberrometry using Zywave II. CXL was performed per ‘Dresden protocol’ through a 30-minutes exposure to 370 nm UVA with an irradiance of 3 mW/cm 2. Patients had comprehensive ophthalmic evaluation after 6 months with special attention to: UDVA, BSCVA, MRSE, corneal topography and wave-front aberrometry changes. Results: The mean age was 25.5±5.84 (20:31) years. After 6 months, there was a significant decrease in corneal thickness from 493.2± 24.17µ to 486.7±24.26µ (P<0.05) and a significant decrease in K max from 47.4±1.17D to 46.1±1.17D (P<0.05). BSCVA improved from preoperative value (0.00:0.5 logMAR (median 0.3)) to 6 months’ value (0.1:1.00 logMAR (median 0.2) (P <0.05). Preoperative MRSE was -7.25: -0.5D (median -2.85D) and at 6 months was -6.25: -0.5D (median - 2.125D) (P<0.05). A significant correlation was found at 6 months between changes in both BSCVA and: K max (P<0.001), corneal thickness (P<0.05), vertical coma (P<0.001) and trefoil (P<0.001). Conclusions: Improvement in HOA was detected after CXL for KCN. The changes in total, vertical coma and vertical trefoil aberrations were significantly correlated with postoperative improvement in BSCVA. Thus, improvement in HOA profile after CXL is one of the explanations of improvement in visual function after CXL in KCN.

Introduction I have this somewhat diffuse concern that at some point, I am in an appointment procedure ... and people say: ‘He has to ... be on social media, [and] have followers ..., because otherwise he can’t say anything about the field of research, otherwise he won’t identify with it … and we need a direct connection to legitimise our discipline in the population!’ And this is where I think: ‘For God’s sake! No, I really don’t want that.’ (Postdoc) Social media such as Facebook or Twitter have become an integral part of many people’s everyday lives and have introduced severe changes to the ways we communicate with each other and about ourselves. Presenting ourselves on social media and creating different online personas has become a normal practice (Vorderer et al. 270). While social media such as Facebook were at first mostly used to communicate with friends and family, they were soon also used for work-related communication (Cardon and Marshall). Later, professional networks such as LinkedIn, which focus on working relations and career management and special interest networks, such as the academic social networking sites (ASNS) Academia.edu and ResearchGate, catering specifically to academic needs, emerged. Even though social media have been around for more than 15 years now, academics in general and German academics in particular are rather reluctant users of these tools in a work-related context (König and Nentwich 175; Lo 155; Pscheida et al. 1). This is surprising as studies indicate that the presence and positive self-portrayal of researchers in social media as well as the distribution of articles via social networks such as Academia.edu or ResearchGate have a positive effect on the visibility of academics as well as the likelihood of their articles being read and cited (Eysenbach; Lo 192; Terras). Gruzd, Staves, and Wilk even assume that the presence in online media could become a relevant criterion in the allocation of scientific jobs. Science is a field where competition for long-term positions is high. In 2017, only about 17% of all scientific personnel in Germany had permanent positions, and of these 10% were professors (Federal Statistical Office 32). Having a professorship is therefore the best shot at obtaining a permanent position in the scientific field. However, the average vocational age is 40 (Zimmer et al. 40), which leads to a long phase of career-related uncertainty. Directing attention to yourself by acquiring knowledge in the use of social media for professional self-representation might offer a career advantage when trying to obtain a professorship. At the same time, social media, which have been praised for giving a voice to the unheard, become a tool for the exclusion of scholars who might not want or be able to use these tools as part of their work and career-related communication, and might remain unseen and unheard. The author obtained current data on this topic while working on a project on Mediated Scholarly Communication in Post-Normal and Traditional Science under the project lead of Corinna Lüthje. The project was funded by the German Research Foundation (DFG). In the project, German-speaking scholars were interviewed about their work-related media usage in qualitative interviews. Among them were users and non-users of social media. For this article, 16 interviews with communication scholars (three PhD students, six postdocs, seven professors) were chosen for a closer analysis, because of all the interviewees they described the (dis)advantages of career-related social media use in the most detail, giving the deepest insights into whether social media contribute to a social exclusion of academics or not. How to Define Social Exclusion (in Academia)? The term social exclusion describes a separation of individuals or groups from mainstream society (Walsh et al.). Exclusion is a practice which implies agency. It can be the result of the actions of others, but individuals can also exclude themselves by choosing not to be part of something, for example of social media and the communication taking part there (Atkinson 14). Exclusion is an everyday social practice, because wherever there is an in-group there will always be an out-group. This is what Bourdieu calls distinction. Symbols and behaviours of distinction both function as signs of demarcation and belonging (Bourdieu, Distinction). Those are not always explicitly communicated, but part of people’s behaviour. They act on a social sense by telling them how to behave appropriately in a certain situation. According to Bourdieu, the practical sense is part of the habitus (Bourdieu, The Logic of Practice). The habitus generates patterns of action that come naturally and do not have to be reflected by the actor, due to an implicit knowledge that is acquired during the course of (group-specific) socialisation. For scholars, the process of socialisation in an area of research involves the acquisition of a so-called disciplinary self-image, which is crucial to building a disciplinary identity. In every discipline it contains a dominant disciplinary self-image which defines the scientific perspectives, practices, and even media that are typically used and therefore belong to the mainstream of a discipline (Huber 24). Yet, there is a societal mainstream outside of science which scholars are a part of. Furthermore, they have been socialised into other groups as well. Therefore, the disciplinary mainstream and the habitus of its members can be impacted upon by the societal mainstream and other fields of society. For example, societally mainstream social media, such as Twitter or Facebook, focussing on establishing and sustaining social connections, might be used for scholarly communication just as well as ASNS. The latter cater to the needs of scholars to not just network with colleagues, but to upload academic articles, share and track them, and consume scholarly information (Meishar-Tal and Pieterse 17). Both can become part of the disciplinary mainstream of media usage. In order to define whether and how social media contribute to forms of social exclusion among communication scholars, it is helpful to first identify in how far their usage is part of the disciplinary mainstream, and what their including features are. In contrast to this, forms of exclusion will be analysed and discussed on the basis of qualitative interviews with communication scholars. Including Features of Social Media for Communication Scholars The interviews for this essay were first conducted in 2016. At that time all of the 16 communication scholars interviewed used at least one social medium such as ResearchGate (8), Academia.edu (8), Twitter (10), or Facebook (11) as part of their scientific workflow. By 2019, all of them had a ResearchGate and 11 an Academia.edu account, 13 were on Twitter and 13 on Facebook. This supports the notion of one of the professors, who said that he registered with ResearchGate in 2016 because "everyone’s doing that now!” It also indicates that the work-related presence especially on ResearchGate, but also on other social media, is part of the disciplinary mainstream of communication science. The interviewees figured that the social media they used helped them to increase their visibility in their own community through promoting their work and networking. They also mentioned that they were helpful to keep up to date on the newest articles and on what was happening in communication science in general. The usage of ResearchGate and Academia.edu focussed on publications. Here the scholars could, as one professor put it, access articles that were not available via their university libraries, as well as “previously unpublished articles”. They also liked that they could see "what other scientists are working on" (professor) and were informed via e-mail "when someone publishes a new publication" (PhD student). The interviewees saw clear advantages to their registration with the ASNS, because they felt that they became "much more visible and present" (postdoc) in the scientific community. Seven of the communication scholars (two PhD students, three postdocs, two professors) shared their publications on ResearchGate and Academia.edu. Two described doing cross-network promotion, where they would write a post about their publications on Twitter or Facebook that linked to the full article on Academia.edu or ResearchGate. The usage of Twitter and especially Facebook focussed a lot more on accessing discipline-related information and social networking. The communication scholars mentioned that various sections and working groups of professional organisations in their research field had accounts on Facebook, where they would post news. A postdoc said that she was on Facebook "because I get a lot of information from certain scientists that I wouldn’t have gotten otherwise". Several interviewees pointed out that Twitter is "a place where you can find professional networks, become a part of them or create them yourself" (professor). On Twitter the interviewees explained that they were rather making new connections. Facebook was used to maintain and intensify existing professional relationships. They applied it to communicate with their local networks at their institute, just as well as for international communication. A postdoc and a professor both mentioned that they perceived that Scandinavian or US-American colleagues were easier to contact via Facebook than via any other medium. One professor described how he used Facebook at international conferences to arrange meetings with people he knew and wanted to meet. But to him Facebook also catered to accessing more personal information about his colleagues, thus creating a new "mixture of professional respect for the work of other scientists and personal relationships", which resulted in a "new kind of friendship". Excluding Features of Social Media for Communication Scholars While everyone may create an Academia.edu, Facebook, or Twitter account, ResearchGate is already an exclusive network in itself, as only people working in a scientific field are allowed to join. In 2016, eight of the interviewees and in 2019 all of them had signed up to ResearchGate. So at least among the communication scholars, this did not seem to be an excluding factor. More of an issue was for one of the postdocs that she did not have the copyright to upload her published articles on the ASNS and therefore refrained from uploading them. Interestingly enough, this did not seem to worry any of the other interviewees, and concerns were mostly voiced in relation to the societal mainstream social media. Although all of the interviewees had an account with at least one social medium, three of them described that they did not use or had withdrawn from using Facebook and Twitter. For one professor and one PhD student this had to do with the privacy and data security issues of these networks. The PhD student said that she did not want to be reminded of what she “tweeted maybe 10 years ago somewhere”, and also considered tweeting to be irrelevant in her community. To her, important scientific findings would rather be presented in front of a professional audience and not so much to the “general public”, which she felt was mostly addressed on social media. The professor mentioned that she had been on Facebook since she was a postdoc, but decided to stop using the service when it introduced new rules on data security. On one hand she saw the “benefits” of the network to “stay informed about what is happening in the community”, and especially “in regards to the promotion of young researchers, since some of the junior research groups are very active there”. On the other she found it problematic for her own time management and said that she received a lot of the posted information via e-mail as well. A postdoc mentioned that he had a Facebook account to stay in contact with young scholars he met at a networking event, but never used it. He would rather connect with his colleagues in person at conferences. He felt people would just use social media to “show off what they do and how awesome it is”, which he did not understand. He mentioned that if this “is how you do it now … I don't think this is for me.” Another professor described that Facebook "is the channel for German-speaking science to generate social traffic”, but that he did not like to use it, because “there is so much nonsense ... . It’s just not fun. Twitter is more fun, but the effect is much smaller", as bigger target groups could be reached via Facebook. The majority of the interviewees did not use mainstream social media because they were intrinsically motivated. They rather did it because they felt that it was expected of them to be there, and that it was important for their career to be visible there. Many were worried that they would miss out on opportunities to promote themselves, network, and receive information if they did not use Twitter or Facebook. One of the postdocs mentioned, for example, that she was not a fan of Twitter and would often not know what to write, but that the professor she worked for had told her she needed to tweet regularly. But she did see the benefits as she said that she had underestimated the effect of this at first: “I think, if you want to keep up, then you have to do that, because people don’t notice you.” This also indicates a disciplinary mainstream of social media usage. Conclusion The interviews indicate that the usage of ResearchGate in particular, but also of Academia.edu and of the societal mainstream social media platforms Twitter and Facebook has become part of the disciplinary mainstream of communication science and the habitus of many of its members. ResearchGate mainly targets people working in the scientific field, while excluding everyone else. Its focus on publication sharing makes the network very attractive among its main target group, and serves at the same time as a symbol of distinction from other groups (Bourdieu, Distinction). Yet it also raises copyright issues, which led at least one of the participants to refrain from using this option. The societal mainstream social media Twitter and Facebook, on the other hand, have a broader reach and were more often used by the interviewees for social networking purposes than the ASNS. The interviewees emphasised the benefits of Twitter and Facebook for exchanging information and connecting with others. Factors that led the communication scholars to refrain from using the networks, and thus were excluding factors, were data security and privacy concerns; disliking that the networks were used to “show off”; as well as considering Twitter and Facebook as unfit for addressing the scholarly target group properly. The last statement on the target group, which was made by a PhD student, does not seem to represent the mainstream of the communication scholars interviewed, however. Many of them were using Twitter and Facebook for scholarly communication and rather seemed to find them advantageous. Still, this perception of the disciplinary mainstream led to her not using them for work-related purposes, and excluding her from their advantages. Even though, as one professor described it, a lot of information shared via Facebook is often spread through other communication channels as well, some can only be received via the networks. Although social media are mostly just a substitute for face-to-face communication, by not using them scholars will miss out on the possibilities of creating the “new kind of friendship” another professor mentioned, where professional and personal relations mix. The results of this study show that social media use is advantageous for academics as they offer possibilities to access exclusive information, form new kinds of relations, as well as promote oneself and one’s publications. At the same time, those not using these social media are excluded and might experience career-related disadvantages. As described in the introduction, academia is a competitive environment where many people try to obtain a few permanent positions. By default, this leads to processes of exclusion rather than integration. Any means to stand out from competitors are welcome to emerging scholars, and a career-related advantage will be used. If the growth in the number of communication scholars in the sample signing up to social networks between 2016 to 2019 is any indication, it is likely that the networks have not yet reached their full potential as tools for career advancement among scientific communities, and will become more important in the future. Now one could argue that the communication scholars who were interviewed for this essay are a special case, because they might use social media more actively than other scholars due to their area of research. Though this might be true, studies of other scholarly fields show that social media are being applied just the same (though maybe less extensively), and that they are used to establish cooperations and increase the amount of people reading and citing their publications (Eysenbach; Lo 192; Terras). The question is whether researchers will be able to avoid using social media when striving for a career in science in the future, which can only be answered by further research on the topic. References Atkinson, A.B. “Social Exclusion, Poverty and Unemployment.” Exclusion, Employment and Opportunity. Eds. A.B. Atkinson and John Hills. London: London School of Economics and Political Science, 1998. 1–20. Bourdieu, Pierre. Distinction: A Social Critique of the Judgement of Taste. Cambridge, Massachusetts: Harvard UP, 1984. ———. The Logic of Practice. Stanford, California: Stanford UP, 1990. 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