3088 Background: We studied clinical and radiological parameters influencing DIP in patients (pts) participating in phase I clinical trials, aiming to investigate predictive factors affecting DIP, in particular those affecting outcome. Methods: 2439 consecutive stage IV cancer pts on phase I clinical trials from 2007 to 2017 were identified. Pts with respiratory symptoms or abnormal lung imaging were reviewed in detail, with longitudinal analysis of imaging by an experienced radiologist. R-DIP was categorized according to internationally recognized criteria. Results: 60 pts developed R-DIP (overall incidence 2.5%); most frequent in pts receiving drug conjugates (31.1%) followed by targeted therapies (8.3%). Hypersensitivity pneumonitis was most common (33.3%) followed by non-specific interstitial pneumonitis (30%) and cryptogenic organising pneumonitis (26.7%). 45% pts who developed R-DIP were clinically asymptomatic. The number of affected lobes (OR 1.47, 95% CI: 1.19-1.81, p < 0.001) and the pattern of R-DIP (OR 5.83 for ARDS, 95% CI: 0.38-90.26, p = 0.002) were significantly associated with a higher CTCAE pneumonitis grading. 23% pts (14/60) had investigational medicinal product (IMP) temporarily discontinued or had a dose reduction while 42% pts (25/60) had IMP permanently discontinued. 48% pts were treated with steroids. The number of affected lobes, pattern of R-DIP and steroid therapy did not influence an improvement in R-DIP (p = 0.65, 0.27 and 0.23 respectively). Continuation of treatment resulted in worsening of DIP in 42.9% of cases. The only predictive factor for an improvement in DIP was an interruption of treatment (OR 0.05, 95% CI: 0.01-0.35, p = 0.01). 14 pts were retreated with a reoccurrence of R-DIP in 4 pts (28.6%). Conclusions: R-DIP from novel agents in early phase clinical trials presents in varied radiological patterns, with findings often preceding clinical symptoms. Treatment interruption leads to improvement of DIP and should be considered early. Close clinical and radiological surveillance is recommended should IMP be restarted.

Patients with Gaucher type 1 (GD1) throughout Argentina were enrolled in the Argentine bone project to evaluate bone disease and its determinants. We focused on presence and predictors of bone lesions (BL) and their relationship to therapeutic goals (TG) with timing and dose of enzyme replacement therapy (ERT). A total of 124 patients on ERT were enrolled in a multi-center study. All six TG were achieved by 82% of patients: 70.1% for bone pain and 91.1% for bone crisis. However, despite the fact that bone TGs were achieved, residual bone disease was present in 108 patients on ERT (87%) at time 0. 16% of patients showed new irreversible BL (bone infarcts and avascular osteonecrosis) despite ERT, suggesting that they appeared during ERT or were not detected at the moment of diagnosis. We observed 5 prognostic factors that predicted a higher probability of being free of bone disease: optimal ERT compliance; early diagnosis; timely initiation of therapy; ERT initiation dose ≥45 UI/kg/EOW; and the absence of history of splenectomy. Skeletal involvement was classified into 4 major phenotypic groups according to BL: group 1 (12.9%) without BL; group 2 (28.2%) with reversible BL; group 3 (41.9%) with reversible BL and irreversible chronic BL; and group 4 (16.9%) with acute irreversible BL. Our study identifies prognostic factors for achieving best therapeutic outcomes, introduces new risk stratification for patients and suggests the need for a redefinition of bone TG. Am. J. Hematol. 91:E448-E453, 2016. © 2016 Wiley Periodicals, Inc.

BACKGROUND Doxorubicin/bleomycin/vinblastine/dacarbazine (ABVD) plus involved-field radiation therapy (IFRT) is the gold-standard treatment for early and advanced stages of Hodgkin lymphoma (HL). We evaluated the outcomes of patients according to prognosis at diagnosis and over time to determine who achieved complete remission (CR). PATIENTS AND METHODS Treatment-naive patients under the age of 75 years at all stages of HL were eligible. The favorable group (FG) contained patients with stage IA-IIIA disease without bulky areas who achieved CR after the third cycle of ABVD. They received only IFRT at 25 Gy. Patients in the unfavorable group (UG) exhibited stages IIIB and IV HL. The UG also included all patients with bulky disease and the subset of the FG without CR after 3 cycles of ABVD, ie, slow responders (FGSR). The UG received 6 cycles of ABVD plus IFRT at 30 Gy to bulky areas at diagnosis or to those areas remaining positive after the third cycle of ABVD. RESULTS In total, 584 patients were evaluable: 285 of them belonged to the FG, and 299 to the UG. Rates of CR were 98% and 85% for the FG and the UG, respectively (P < .001). Sixty patients in the FG received 6 cycles of ABVD because they had not achieved CR after 3 cycles (ie, the FGSR subgroup). The 5-year event-free survival rate was 89% for the FG, 66% for the FGSR, and 72% for the UG (P < .001). The overall survival at 5 years was significantly better for the FG (98%) than for the FGSR (87%) and the UG (88%; P < .001). CONCLUSION Patients from the FG demonstrated excellent outcomes compared with those from the FGSR and UG, despite receiving less chemotherapy and fewer doses of IFRT.

GT 267-004 is a nonabsorbed, nonantibiotic, high molecular weight anionic polymer that is undergoing clinical evaluation as a Clostridium difficile toxin sequestrant. The active pharmaceutical ingredient (API) is a mixed salt form that consists of approximately 30 to 50% potassium and 70 to 50% sodium as the counterions on the polymer. The initial polymerization process results in an aqueous polymer solution with the polymer in the 100% sodium form. This article describes the use of two innovative approaches, electrodialysis (ED) and ion exchange using ion exchange resins (IXR), to convert the single-salt polymer to the mixed-salt form. Electrodialysis experiments were conducted using a stack of five cells, each of which contained two cation and one anion exchange membranes. The electrodialysis was run in batch mode with a sodium chloride solution as the concentrate stream and a potassium chloride solution as the diluate stream. The ED process was monitored on-line by measuring the conductivity of the streams. Yield loss of the API through the ED membranes was minimal. The ED process was found to be fast, efficient, and reproducible. The ion exchange experiments were conducted using a strong acid cation resin in the potassium form. By using a fixed bed column mode, an appropriate amount of ion exchange was carried out to produce the mixed-salt API in the effluent stream. The resin bed could be regenerated using KCl solution and reused for subsequent batches of polymer solution. The recovery of the API in the product solution was excellent. The ion exchange route was used to synthesize radio-labeled API for clinical trials.

In the sugar and starch industries, increasing constraints could require producers to significantly modify their manufacturing processes. As main trends, we can mention reduction of the environmental impact of these processes regarding liquid and solid waste discharge, potential alternatives to the use of lime to achieve savings in operating costs and getting value out of the by-products. In this context, this presentation focuses on the introduction of innovative technologies that can potentially replace conventional processes, such as rotary filters, IX resins, centrifugation, etc. These allow Eurodia to propose cost-effective solutions while meeting the above-mentioned requirements. Operating for several years in European mills, the following technologies will be described: (1) Clarification of diffusion juices by crossflow microfiltration with Scepter® membranes. While the capital investment might be 50% higher with microfiltration, the operating costs are two times lower than rotary filters, and fixed costs are comparable. (2) Demineralization and purification by conventional electrodialysis (ED). Compared with IX resins, this technology allows mainly a reduction of the pollution load and an improvement of the sugar yield. (3) Separation of sugars from non-sugars by the Improved Simulated Moving Bed (ISMB®) process. This type of chromatography allows high separation yields at lower capital and running costs than traditional simulated moving bed chromatography. These three techniques were supplied by Eurodia Industrie in European plants and are the basis of innovative process combinations for the production of sugars or starch derivatives.

This two-part report reviews the benefits of systems that combine several convential separation techniques, such as distillation, electrodialysis and membrane- and solvent-based systems, for improved results. Part 1 (p. 46-50) profiles a hybrid strategy for removing CO 2 from natural gas, while Part 2 (p. 51-53) discusses a hybrid separation scheme for producing organic acids.