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Involvement of the central nervous system (CNS) is a rare complication of multiple myeloma (MM). Herein, we have described the incidence, characteristics, prognostic factors for post CNS-MM survival, and outcome of CNS-MM and explored the efficacy of novel agents (NA) (thalidomide, bortezomib, lenalidomide) in this setting. Between 2000 and 2013, 31 (0.9 %) out of 3408 newly diagnosed symptomatic MM patients, consecutively diagnosed and treated during the same period in 12 Greek centers, developed CNS-MM (M/F 15/16, median age 59 years, range 20-96 years; newly diagnosed/relapsed-refractory 2/29; median time to CNS-MM diagnosis 29 months). Clinical and laboratory characteristics were retrospectively recorded. Twenty-six percent of patients had circulating plasma cells (PCs) or plasma cell leukemia (PCL) at CNS-MM and 39 % had skull-derived plasmacytomas, suggesting hematological and contiguous spread. Treatment for CNS-MM was offered in 29/31 patients and 11/29 responded (NA 18/29, additional radiotherapy 9/28, intrathecal chemotherapy 13/29). The median post CNS-MM survival was 3 months (95 % CI 1.9-4.1) and did not differ between patients treated with NA and/or radiotherapy vs. others. In the multivariate analysis, prior treatment of MM with NA, extramedullary disease (EMD) during MM course (i.e., plasmacytomas, circulating PCs, or documented PCL) and abnormally high LDH at MM diagnosis were independent prognostic factors, whereas treatment of CNS-MM with NA did not predict for post CNS-MM survival. Despite the relatively limited number of patients due to the rarity of CNS-MM, our results suggest that NA do not seem to improve post CNS-MM survival. Patients with EMD display shortened post CNS-MM survival and should be followed thoroughly.

We have studied the efficacy and the prognostic impact of novel agents in 50 primary plasma cell leukemia (pPCL) patients registered in our database. Eighty percent of patients were treated upfront with novel agent-based combinations; 40% underwent autologous stem cell transplantation (ASCT). Objective response rate was 76; 38% achieved at least very good partial response (≥vgPR) and this correlated significantly with bortezomib-based therapy plus ASCT. At the time of evaluation, 40 patients had died. Early mortality rate (≤1 month) was 6%. Median progression-free survival (PFS) and overall survival (OS) were 12 months and 18 months respectively, both significantly longer in patients treated with bortezomib-based therapy + ASCT vs. others (PFS: 18 vs. 9 months; p = 0.004, OS: 48 vs. 14 months; p = 0.007). Bortezomib-based therapy + ASCT predicted for OS in univariate analysis. In multivariate analysis, achievement of ≥vgPR and LDH ≥ 300 U/L were significant predictors for OS. These real-world data, based on one of the largest reported national multicenter series of pPCL patients treated mostly with novel agents support that, among the currently approved induction therapies, bortezomib-based regimens are highly effective and reduce the rate of early mortality whereas in combination with ASCT consolidation they prolong OS.

The purpose of this study was to develop a framework for analyzing and evaluating student-constructed models of physical phenomena and monitoring the progress of these models. Moreover, we aimed to examine whether this framework could capture differences between models created using different computer-based modeling tools; namely, computer-based programming environments which, in prior research, were found to differ in various aspects of the models constructed through them. We analyzed 220 computer-based models of physical phenomena developed by two groups of elementary-school students. Using open coding we developed a framework that includes five elements of scientific models that code for representations of: (i) the physical objects; (ii) the physical entities; (iii) the object behaviors; (iv) the interactions among physical objects, physical entities, and object behavior(s); and (v) the accuracy of the phenomenon depiction. The implementation of this framework confirmed that it can differentiate student-generated models according to their sophistication and structural components, independent of the computer-based programming environments used to create the models.

948 Renal impairment (RI) is a common presenting complication of multiple myeloma (MM) and is associated with increased risk of treatment related toxicity and early death. The management of RI in patients with MM requires vigorous supportive measures and the immediate institution of antimyeloma therapy. After the introduction of novel agents a significant improvement of the survival of patients with MM has been observed; however, the impact of these therapies on the survival of MM patients who present with RI has not been extensively studied. In order to analyze the impact of RI in newly diagnosed patients with MM over the past 20 years, we analyzed 1773 patients with symptomatic myeloma who were treated within the Greek Myeloma Study Group (GMSG). Patients were divided in groups according to the date of initial treatment (1/1/1990-31/12/1994, 1/1/1995-31/12/1999, 1/1/2000-31/12/2004, after 1/1/2005). Thalidomide became available in Greece after 1/1/2000 and bortezomib after 1/1/2005. eGFR was calculated by the modified MDRD formula and the degree of RI was rated as severe when eGFR was <30 ml/min, moderate when eGFR was 30–59 ml/min and mild (or no RI) when eGFR >60 ml/min. The frequency of RI over time was similar as well as the proportion of patients who presented with severe RI (17% vs. 21% vs. 17% vs. 19%) for the respective time periods (p=0.496). More patients >65 years started therapy after 2000 (44% vs. 50% vs. 59% vs. 59%, respectively, p<0.001), especially patients >75 years (13% vs. 18% vs. 24% vs. 32%, respectively, p<0.001). Anemia (Hb <10 g/dl; p=0.007) and ISS-3 disease (p=0.001) were more common after 1/1/1995; there were no other significant differences in the characteristics of the patients during the respective time periods. No patients received upfront novel agents before 31/12/1999, while 20% received upfront novel agent in the period 2000–2004 (almost exclusively thalidomide) and 73% after 1/1/2005 (mostly thalidomide and bortezomib). Myeloma response (≥PR) to frontline therapy was achieved in 56.5% & 54% of patients in the period 1990–1994 & 1995–1999 vs. 67% and 72% of patients in the periods 2000–2004 and after 2005 (p<0.001). The median survival of patients has improved significantly during the past 20 years: 39 months (1990-1994), 31 months (1995-1999), 40.5 months (2000-2004), 54 months after 2005 (p<0.001). The median OS for patients with severe RI has improved significantly from 18 months & 19.5 months in the 1990–1994 & 1995–1999 to 29 months and 32 months for the periods 2000–2004 and after 2005 (p=0.005). For patients with moderate RI the OS improved from 33 & 26 months between 1990–1994 & 1995–1999 to 40 & 44 months in the periods 2000–2004 and after 2005 (p=0.003). For patients with an eGFR ≥60 ml/min the OS improvement was less pronounced (48.5 months vs. 45 months vs. 51 months for the periods 1990–1994 & 1995–1999 & 2000–2004 respectively (p=0.076) and only after 2005 a significant improvement in OS is observed (median OS has not been reached; 3-year OS rate is 73%, p<0.001). For patients with severe RI early death rates (<2 months from initiation of therapy) were 12% vs. 7% for patients with moderate RI vs. 3% for patients with mild or no RI (p<0.001) and remained unchanged over time. We then adjusted for differences between groups in a multivariate model: treatment after 1/1/2000 was independently associated with improved survival compared to patients treated before 31/12/1999 (p<0.001). After adjusting for the degree of RI in the model, the hazards ratios (HR) for death for patients with severe RI for the 2000–2004 and after 2005 periods were 0.485 & 0.387 respectively compared to patients treated before 2000 (p<0.001 for both comparisons). For patients with moderate RI the respective HRs were 0.65 (p=0.003) & 0.57 (p=0.001), while for patients with mild or no RI the HRs were 0.85 (p=0.1) & 0.66 (p=0.003) for the 2000–2004 and after 2005 periods, respectively. In conclusion, the incidence of RI at diagnosis of MM has remained unchanged during the past 20 years, despite the increasing numbers of older patients who are diagnosed and treated for MM. The risk of early death is almost 2 to 4-fold higher in patients with severe RI vs. patients with moderate or no RI and has not improved over time. However, after the introduction of novel therapies there has been a significant improvement of the survival of patients with RI, which is more pronounced in patients with severe RI. Disclosures: No relevant conflicts of interest to declare.

Patients ≥ 80 years of age present with features of advanced myeloma and impaired performance status. The addition of novel agents may improve their outcome, but careful assessment and prospective clinical trials targeting the population of elderly patients are needed.

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cell nuclear antigen, the recurrence rate, and the progression of invading tumour). Specimens investigated for tenascin expression from patients with superficial bladder cancers were categorized into 28 treated by TURBT only and 53 who had TURBT followed by intravesical instillations of interferon. RESULTSCytoplasmic tenascin expression was detected in tumour cells in 20% of specimens. Tenascin was expressed in the tumour stroma in 76% of specimens, and was positively correlated with tumour grade and stage. Stromal tenascin expression was positively correlated with proliferative activity, and with the expression of fibronectin and collagen type IV. Fibronectin was expressed in the tumour stroma in 89% of specimens and was positively correlated with tumour stage, proliferative activity, and expression of collagen type IV and laminin. Collagen type IV was expressed in 93% of specimens, and was positively correlated with tumour grade and stage. Laminin was expressed in 78% of specimens and had no significant correlation with the clinicopathological features. Patients treated with TURBT alone and who had low levels of tenascin had a longer tumour-free interval than those with high levels of tenascin.