ALBERT

Description: New seismic and well data in the deep-water basins of Campos, Santos, South Kwanza and Benguela, supported by plate reconstructions, help answer fundamental questions on the rifting history of the central South Atlantic, specifically on the amount and effect of fault-related deformation, and on when and where sea-floor spreading started. The Paraná mantle plume played a fundamental role – dynamically raising the plate, prolonging continental rifting by heat-softening the crust and, after break-up, delaying the onset of marine conditions. Previous discrepancies in extension and subsidence have been solved, and the location and age of the continent–ocean boundary can now be determined. Rifting involved approximately 450 km of homogeneous pure shear, equivalent to a β factor (lithosphere stretching factor) of 4.5. Break-up occurred at 123 Ma (Barremian–Aptian boundary), 7–8 Ma later than the southern South Atlantic but 6 Ma before widespread salt deposition. The mid-Atlantic ridge was initially subaerial, marked by a volcanic high. Sea-floor spreading was at a rate of 24 mm year−1, similar to syn-rift deformation prior to break-up. Transcontinental strike-slip shear zones are not evident but a major NW–SE lithospheric lineament associated with a failed triple junction arm had a major influence on the magmatic history, both prior to and after break-up.Supplementary material: A4 versions of the seismic sections shown in Figures 6 & 7 are available at http://www.geolsoc.org.uk/SUP18563.

Description: Background: Polycythemia vera (PV), essential thrombocythemia (ET) and myelofibrosis (MF) are clonal hematological disorders collectively named as myeloproliferative neoplasms (MPN). Discovery of JAK2 mutation in 2005, altered WHO classification for MPN diagnosis in 2008 and availability of new treatment of MPN may have substantial effect on epidemiology of MPN. Published data on epidemiology of MPN after the discovery of JAK2 mutation and the introduction of 2008 WHO classifications for MPN, in particular on the prevalence of MPN, are scarce. We aimed to study the epidemiology of MPN in Norway and to explore the impact of JAK-2 mutation and new guidelines on the incidence of MPN using data from the Norwegian cancer registry. Method: We identified 2344 persons diagnosed with MPN from the Norwegian Cancer Registry diagnosed between 1995 and 2012. Registration of cancer in the Norwegian Cancer Registry is mandatory according to the law. We report age-adjusted incidence, prevalence and relative survival of MPN. Age adjusted incidence was reported for 2 years periods from 1995 to 2012. The prevalence was calculated according to the Norwegian population per 31.12.2011. Results: A total of 945 cases of PV was identified with a median age at diagnosis of 70 years; 471 males (50%) and 474 females (50%). The overall age-adjusted incidence rate both genders was 0.4/10⁵ in 1995-1997, 0.5/10⁵ in 1998-2000, 0.7/10⁵ in 2001-2003, 0.8/10⁵ in 2004-2007, 2008-2009 and 0.7/10⁵ in 2010-12. We identified a total of 762 cases of ET with a median age at diagnosis of 65 years, 297 males (39%) and 465 females (61%). The overall age adjusted incidence rate both genders being 0.3/10⁵ in 1995-1997 and 1998-2000, 0.5/10⁵ in 2001-2003 and 2004-2006, 0.9/10⁵ in 2007-2009 and 2010-2012. A total of 418 cases of MF was identified with a median age at diagnosis of 71 years; 243 males (58%) and 175 females (42%). Age adjusted incidence rates of both genders were 0.2/10⁵ from 1995-2006, 0.3/10⁵ in 2007-2009 and 0.5/10⁵ in 2010-2012. There were a total of 219 persons with unclassified MPN both genders,119 males (54%) and 100 females (46%) and age adjusted incidence rate varied from 0.1-0.2 to 0.1/10⁵ 1995-2012. Per 31.12.2011 the prevalence of PV, ET and MF was 9.2, 8.6 and 3.0 per 10⁵ inhabitants respectively. The survival curves for males and females for the three conditions are shown in the figure. Conclusions: This population-based study shows that the incidence of ET and MF almost doubled during the years 2007-2012 as compared to 1995-2006 as shown in the table. This increment in the incidence may possibly be related to improved diagnostics including the JAK2 mutation and the introduction of 2008 WHO-guidelines for MPN. Surprisingly, the discovery of JAK2 does not seem to have had impact on the incidence of PV as indicated by steady incidence rates since 2001. The relative survival was only slightly reduced for PV and ET, but substantially reduced for MF. Only 50% of patients with MF survive for more than 5 years. Table Incidence of MPN per 105 inhabitants during the period 1995 to 2012 in Norway 1995-97 1998-2000 2001-03 2004-06 2007-09 2010-12 PV 0.4 0.5 0.7 0.8 0.8 0.7 ET 0.3 0.3 0.5 0.5 0.9 0.9 MF 0.2 0.2 0.2 0.2 0.3 0.5 Figure showing the relative survival of PV, ET and MF Figure. showing the relative survival of PV, ET and MF Disclosures Roaldsnes: Novartis Norge AS: Research Funding. Ghanima:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Description: Background With an aging population, the burden of comorbidity in AML patients is expected to increase. Evidence on how to integrate comorbidity and functional status into clinical decision making is sparse and prior studies have been predictive and limited by single center study design, and small sample sizes. Objectives To examine the impact of comorbidity and WHO Performance Status (PS) on intent of treatment in Danish AML patients. Secondary, to determine the prognostic impact of comorbidity and PS on achievement of complete remission, short- and long-term mortality in AML patients treated with curative intent. Methods In a nationwide cohort study, we identified all AML (non-promyelocytic leukemia) patients diagnosed in Denmark from 2000-2013 using a population-based leukemia registry (n=2785) which prospectively collects clinical data. We excluded patients with unknown intent of treatment (n=25). We identified comorbid conditions through the Danish National Registry of Patients. Comorbidity was evaluated according to presence of 17 of the 19 chronic diseases (HIV and leukemia excluded) in the Charlson Comorbidity Index with separate adjustment for all diseases associated with secondary AML (modified CCI (mCCI)). Crude and adjusted odds ratios (OR) and corresponding 95% confidence intervals (CI) for receiving treatment with curative intent were estimated. We used Cox proportional hazards regression to assess the influence of comorbidity and performance status on 90-day and 90-day to 3-year mortality in patients treated with curative intent (n=1444) by estimating crude and adjusted mortality ratios (MRs) and corresponding 95% CIs. We adjusted for age, gender, leukocyte count, prior chemo-/radiotherapy, and prior hematological diseases. Results Of 2760 patients 52% were treated with curative intent. Median age was 69 years (palliative intent: 78 vs. curative intent: 58). Overall, 60% of patients did not have any comorbidity, 26% had 1 comorbid disease, and 13% had 2 or more comorbidities. In patients treated with curative intent, the corresponding prevalences were 76%, 19%, and 6%. Overall, 26% of patients had PS=0, 42% had PS=1, and 32% had PS ≥2. The corresponding figures in patients treated with curative intent were 33%, 47%, and 20%. Dementia and heart failure were the two individual comorbid diseases most strongly associated with opting-out of intensive treatment (prevalence ratio 0.11 (95%CI 0.01-0.67) and 0.24 (95%CI 0.15-0.37). In patients treated with curative intent, those with comorbidity had lower complete remission rate than those without comorbidity, 66% (95%CI 60.7-70.7) vs. 74% (95%CI 70.8-76.9) whereas choice of chemotherapy regimen and dose did not differ. Compared to patients without comorbidity (mCCI=0), the adjusted ORs for treatment with curative intent were 0.57 (95%CI 0.41-0.73) for patients with 1 comorbid disease and 0.32 (95%CI 0.22-0.47) for 2 or more. Compared to patients with PS=0, the adjusted ORs of treatment with curative intent were 0.80 (95%CI 0.58-1.09) for PS 1, 0.45 (95%CI 0.31-0.65) for PS 2, and 0.09 (95%CI 0.05-0.14) for PS≥3. Crude survival curves according to comorbidity and PS are shown below. Crude and adjusted MRs are listed in table 1. Conclusions The chance of being allocated to intensive chemotherapy decreased dramatically with increasing number of comorbid diseases and increasing PS. Surprisingly, among patients treated with curative intent presence of comorbidity was not associated with an increase in short-term mortality, and if any, only a slight increase in long-term mortality. High PS was strongly associated with both short- and long-term mortality. Our findings may be explained by the selection process before treatment with curative intent and raises the question whether more patients with comorbidity and low PS at time of diagnosis may benefit from intensive treatment. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 1477 Previous studies have documented the underrepresentation of women and elderly patients in American clinical trials of leukemia. If, characteristics of patients included in clinical protocols differ markedly from the characteristics of the majority of patients treated outside protocols the external validity of clinical trials may be threatened. Methods: The Danish National Acute Leukaemia Database (ALDB) includes detailed data on a large well-defined non-selected population of 2729 AML patients (covering 〉95% of AML patients diagnosed since Jan 2000). Since 2000 Danish AML patients have been included in 3 different British protocols (AML15, 16 and 17). We analysed a cohort of 2624 patients diagnosed with AML in Denmark since Jan. 2000 (105 APL-patients were excluded). We compared patients treated with curative intent according to the British protocols with patients treated with curative intent off-protocol with regard to characteristics, possible prognostic factors, CR-rate, and survival. For comparable groups we divided patients into 2 age groups (

Description: Background: ITP is a rare autoimmune disorder characterized by low platelet counts, resulting in an increased risk for bleeding. Paradoxically, patients with cITP may also have an increased incidence of thrombotic or thromboembolic events, but population-based data on this are limited. We estimated the incidence of these events in a prospective cohort study of incident cITP patients in three Nordic countries. Methods: Based on National Health Registry Systems (NHRSs) and medical records in Denmark, Norway, and Sweden, the study cohort included all adults diagnosed with cITP from January 1, 2008 to December 31, 2012 (n=1,821). Arterial thrombotic events (myocardial infarction [MI] and stroke) and venous thromboembolic events (pulmonary embolism and deep vein thrombosis) were identified in the NHRSs. Patients were followed from the latest of cITP diagnosis or April 1, 2009, until the earliest date of the first occurrence of the event of interest, death, emigration, or December 31, 2012. Incidence rates (events per 1,000 person-weeks [PW]) were computed for the entire cohort and stratified by gender, age, splenectomy status, and comorbidity burden. Results: Nearly 60% of the cITP cohort was 〉50 years in age, and 56% were female. Overall, the incidence of arterial thrombotic events was 0.31 per 1,000 PW (95% confidence interval [CI]: 0.25-0.39) and the incidence of venous thromboembolic events was 0.18 per 1,000 PW (95% CI: 0.13-0.24). For arterial thrombotic events, the risk was higher in males (compared with females), and the risk for both event types increased with increasing age and comorbid burden. Given the small number of patients who underwent splenectomy (n=101), it was difficult to detect any differences in the risk of thrombotic events by splenectomy status, but the incidence of venous thromboembolic events was higher in splenectomized versus non-splenectomized patients (0.27 per 1,000 PW [95% CI: 0.15-0.50] versus 0.16 [95% CI: 0.11-0.23]). Conclusions: Among patients with cITP, the risk of arterial thrombotic events is higher in males than females and increases with increasing age and level of comorbid burden. The risk of venous thromboembolic events is heightened in cITP patients who have undergone splenectomy. Abstract 4845. TableArterial thrombotic eventsVenous thromboembolic eventsN / PWIncidence rate per 1,000 PW (95% CI)N / PWIncidence rate per 1,000 PW (95% CI)Overall (n=1,821)68 / 218,3910.31 (0.25-0.39)39 / 220,8650.18 (0.13-0.24)GenderMale (n=794)39 / 90,5310.43 (0.31-0.59)17 / 92,4080.18 (0.11-0.30)Female (n=1,027)29 / 127,8600.23 (0.16-0.33)22 / 128,4570.17 (0.11-0.26)Age18-50 years (n=751)5 / 96,1190.05 (0.02-0.12)5 / 95,9630.05 (0.02-0.13)51-70 years (n=544)13 / 65,6520.20 (0.11-0.34)13 / 65,5560.20 (0.12-0.34)〉70 years (n=526)50 / 56,6210.88 (0.67-1.17)21 / 59,3450.35 (0.23-0.54)Comorbid burdenLow (n=1,243)25 / 154,1810.16 (0.11-0.24)18 / 155,0580.12 (0.07-0.18)Moderate (n=435)29 / 48,3070.60 (0.42-0.86)14 / 49,6940.28 (0.17-0.48)High (n=143)14 / 15,9030.88 (0.52-1.49)7 / 16,1130.43 (0.21-0.91)Splenectomy statusSplenectomized (n=101)10 / 37,1210.27 (0.14-0.50)10 / 36,9570.27 (0.15-0.50)Non-splenectomized (n=1,720)58 / 181,2700.32 (0.25-0.41)29 / 183,9080.16 (0.11-0.23) Disclosures Cetin: Amgen: Employment. Ghanima:Roche: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; GlaxoSmithKline: Consultancy. Stryker:Amgen Inc.: Employment, Equity Ownership.

Description: Few data exist on the long-term prognosis of patients with chronic primary chronic immune thrombocytopenia (ITP). We examined the risk of infections, hemorrhage resulting in hospitalization, hematologic malignancies, and total and cause-specific mortality among patients with ITP compared with the general population. We used population-based medical databases to identify 407 patients with primary chronic ITP diagnosed during 1996 to 2007 and 4069 general population members individually matched on age, sex, and comorbidity level. We used Cox regression analysis to estimate rate ratios (RRs) adjusted for age (≤ 60 or 〉 60 years), sex, calendar year, and level of comorbidity. The adjusted 1-year RR of infection was 4.5 (95% confidence interval [CI], 3.3-6.1) for patients with chronic ITP compared with the general population cohort. The adjusted RR decreased to 1.8 (95% CI, 1.3-2.5) for the second to fifth year of follow-up. The adjusted 5-year RR was 3.2 (95% CI, 1.2-9.0) for hospitalized intracranial hemorrhage, 4.4 (95% CI, 2.3-8.3) for other hospitalized hemorrhages, and 4.7 (95% CI, 1.7-12.7) for hematologic malignancy. The 5-year all-cause mortality RR was 2.3 (95% CI, 1.8-3.0). In summary, primary chronic ITP was associated with substantially increased long-term risk of infections, hemorrhagic episodes requiring hospitalization, hematologic malignancies, and mortality.