ALBERT

Description: Background: The presence of significant marrow fibrosis has previously been shown to be a poor prognostic factor in patients with myelodysplastic syndrome (MDS). Associations between fibrosis and higher transfusion requirements, multilineage dysplasia, and an increased rate of leukaemic transformation have been demonstrated. Currently, the presence of fibrosis is not included in standard risk scores for MDS such as the Revised International Prognostic Scoring System (IPSS-R) nor is fibrosis included in the current WHO classification for MDS. It is also not certain whether the presence of fibrosis should alter current treatment algorithms for patients. More information is needed to further assess both the prognostic and therapeutic implications of the presence of significant fibrosis in this patient population. Methods: We conducted a retrospective study utilizing a database of 247 patients with diagnosed MDS in a single center from 2000-2014. Bone marrow trephine samples for 200 of these patients were assessed using the European consensus on grading bone marrow fibrosis. Data was collected on: age, gender, WHO classification, marrow blast percentage, cytogenetics, progression to AML, treatment with azacitadine, and overall survival. These characteristics were compared between patients without significant fibrosis (grade 0/1) and those with significant fibrosis (grade 2/3). Our aim was to identify potential significant associations with MDS fibrosis and to assess whether treatment with azacitadine influenced these parameters or overall survival between the two groups. Results: Of 200 patients, 38 were found to have significant fibrosis (19%) versus 162 without significant fibrosis (81%). There was no significant difference in age or gender between the two groups. The commonest WHO category in both groups was RCMD (31.58% v 48.77%) in the fibrosis and non-fibrosis groups respectively. IPSS-R score was determined for 152 patients where data was available. There was no significant difference observed in IPSS-R Score between the two groups. Cytogenetic data was available on 175 patients. The commonest cytogenetic result in both groups was normal karyotype (55.3% v 52.5%). In the fibrosis group this was followed by complex cytogenetics (〉 2 abnormalities) (23.68%) and trisomy 8 (7.89%). The presence of a cytogenetic abnormality was not significantly different in those with or without fibrosis (p=0.69). A significant difference was found between patients' marrow blast percentage at diagnosis (average 5.4% blasts in fibrotic patients versus 3.6% in non-fibrotic patients (p=0.04)). There were no differences in diagnostic haemoglobin level, neutrophil count, and platelet count. Acute Myeloid Leukaemia (AML) developed in 31 patients. The presence of fibrosis was associated with an increased rate of AML transformation with 27% compared with 13.5% in patients without fibrosis (p=0.05). Median overall survival was decreased in the fibrosis group compared to the non-fibrosis group (29 months versus 42 months, p=0.02). A total of 36 patients (25 of whom progressed to AML) received azacitadine treatment (9 (24%) patients with fibrosis and 27 (17%) patients without fibrosis). Patients with fibrosis had a longer median survival than those without (29 months and 19 months respectively) but this difference was not statistically significant (p=0.48). Conclusion: Marrow fibrosis adversely affects overall survival in patients with MDS. Patients with fibrosis are more likely to present with higher marrow blast counts and to progress to AML. Patients with fibrosis who received azacitadine appeared to have an overall higher survival than those without fibrosis. However, the numbers of patients who received azacitadine were small. This study confirms the adverse prognostic influence of marrow fibrosis in patients with MDS, but the presence of fibrosis may not adversely affect the responsiveness to azacitadine therapy. Table IPSS-R Score - Fibrosis versus Non-Fibrosis Table. IPSS-R Score - Fibrosis versus Non-Fibrosis Figure Overall Survival (Non-Fibrosis versus Fibrosis) Figure. Overall Survival (Non-Fibrosis versus Fibrosis) Disclosures Desmond: Novartis: Honoraria.

Description: Introduction Social exclusion in Ireland is strongly associated with injecting drug use, particularly injection of opiates into the groin: a strong risk factor for venous thromboembolism (VTE) (O'Reilly et al, 2015). Ní Cheallaigh et al (2017) reported a high burden of disease in socially excluded individuals in Ireland that can be effectively addressed by dedicated service planning and care provision. VTE in socially excluded persons has been identified by our group as a key knowledge gap. We have generated preliminary data demonstrating that socially excluded people account for a significant proportion of patients presenting with VTE in Dublin. Methods We extracted national Hospital InPatient Enquiry (HIPE) data from Health Atlas Ireland using the methods outlined in Kevane et al (2019). We identified individuals as "socially excluded persons" if their records contained one or more of the variables identified by Aldridge et al (2018): homeless individuals, prisoners, sex workers and individuals with substance use disorders. We identified all emergency inpatient hospital admissions for those with any diagnosis of VTE during 2017 using VTE-associated ICD-10 codes. Results There were 494,972 emergency inpatient admissions in patients 〉16 years during this 12 month period, of which 5,717 (1.2%) had a VTE diagnosis (55% of which were DVTs). 306 (5.3%) of hospital episodes with VTE occurred in socially excluded individuals. Applying maximum and minimum assumptions on the estimated population denominator we estimated that overall the annual incidence rate of VTE-related hospitalisation per person was approximately 10-fold higher in socially excluded individuals when compared to the general population (in which it was 0.12%). Conclusions This is the first time that an approximately ten-fold increase in the risk of hospitalisation due to VTE has been shown to be associated with social exclusion. This information was generated from national data, using surrogate identifiers for socially excluded persons. We hypothesise that detailed characterisation of VTE events in socially excluded clients will permit improved service planning and care provision for these vulnerable patients, enabling better VTE prevention and management. This may save lives and prevent the disabling and common long-term consequence of post-thrombotic syndrome with debilitating leg ulcers, which in this population results in numerous admissions and severe mobility issues. Planning such initiatives has the potential to reduce morbidity and mortality, improve quality of life but also to reduce hospital admissions (which are hugely over-represented in this patient group), save costs and resources and most importantly results in more equitable health care for socially excluded patients. Disclosures Ewins: Amgen: Other: Conference Fees & Travel Expenses; Bayer: Other: Conference Fees & Travel Expenses. Ni Ainle:BMS: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Boehringer: Membership on an entity's Board of Directors or advisory committees; Leo Pharma: Research Funding; Actelion: Research Funding. Cliona:Pfizer: Research Funding; MSD: Other: Travel Expenses.

Description: Background Social exclusion, experienced by vulnerable people at the margins of society, causes severe health inequity with dramatically increased risks of chronic disease and reductions in life-expectancy. Health services are not designed to meet the complex needs of socially excluded people (SEP). SEP are frequently unintentionally excluded from large observational studies such as household surveys and surveys requiring active participation (Levitas et al, 2007). This lack of data deepens inequity. Social exclusion in Ireland is strongly associated with injecting drug use, a strong risk factor for venous thromboembolism (VTE) (O'Reilly et al, 2015). Although an increased prevalence of VTE in lower socioeconomic groups has been described (Zoller et al, 2012), the impact of social exclusion and marginalisation on VTE has never been characterised in detail. The Registro Informatizado de Enfermedad TromboEmbólica (RIETE Registry) is the world's largest database on patients with VTE. It was commenced in 2001 and continues to collect prospective data on consecutive patients presenting to hospital with acute VTE events. Patients are followed longitudinally, for a minimum of three months (Bikdeli et al, 2018). One objective of the registry is to provide information on the natural history of VTE - particularly in subgroups of patients who would not usually be recruited to randomised clinical trials. Methods Our group has generated preliminary data (submitted separately to ASH 2019) which demonstrate that people with social exclusion can be identified from large national and international datasets using surrogate identifiers. The RIETE registry already collects several of these data elements that can be used to identify people who are socially excluded: HIV infection (which is strongly associated with injecting drug use), liver disease, chronic alcoholism and chronic psychiatric illness. We adapted the methodology developed in the Irish dataset and interrogated the RIETE registry utilising the available surrogate identifiers. We aimed to estimate the prevalence of social exclusion amongst patients with VTE, and to determine their clinical characteristics, treatment details and outcomes, with the ultimate goal of informing future service-planning and care-provision to this vulnerable group. Results At the time of interrogation of the RIETE registry, 79735 patients with VTE had been enrolled in 24 countries worldwide. Of these, 9211 (12%) met our criteria for SEP due to the presence of one or more of our surrogate identifiers. Of these, 60% presented with pulmonary embolism vs 52% in the non-SEP group (P