Syngeneic transplantation in aplastic anemia: pre-transplant conditioning and peripheral blood are associated with improved engraftment: an observational study on behalf of the Severe Aplastic Anemia and Pediatric Diseases Working Parties of the European Group for Blood and Marrow Transplantation

Aplastic anemia is usually treated with immunosuppression or allogeneic transplant, depending on patient and disease characteristics. Syngeneic transplant offers a rare treatment opportunity with minimal transplant-related mortality, and offers an insight into disease mechanisms. We present here a retrospective analysis of all syngeneic transplants for aplastic anemia reported to the European Group for Blood and Marrow Transplantation. Between 1976 and 2009, 88 patients received 113 transplants. Most transplants (n=85) were preceded by a conditioning regimen, 22 of these including anti-thymocyte globulin. About half of transplants with data available (39 of 86) were followed by posttransplant immunosuppression. Graft source was bone marrow in the majority of cases (n=77). Transplant practice changed over time with more transplants with conditioning and anti-thymocyte globulin as well as peripheral blood stem cells performed in later years. Ten year overall survival was 93% with 5 transplant-related deaths. Graft failure occurred in 32% of transplants. Risk of graft failure was significantly increased in transplants without conditioning, and with bone marrow as graft source. Lack of posttransplant immunosuppression also showed a trend towards increased risk of graft failure, while anti-thymocyte globulin did not have an influence. In summary, syngeneic transplant is associated with a significant risk of graft failure when no conditioning is given, but has an excellent long-term outcome. Furthermore, our comparatively large series enables us to recommend the use of pre-transplant conditioning rather than not and possibly to prefer peripheral blood as a stem cell source

Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): And randomised, phase 3, open-label, multicentre study

Background: Bortezomib with dexamethasone is a standard treatment option for relapsed or refractory multiple myeloma. Carfilzomib with dexamethasone has shown promising activity in patients in this disease setting. The aim of this study was to compare the combination of carfilzomib and dexamethasone with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma. Methods: In this randomised, phase 3, open-label, multicentre study, patients with relapsed or refractory multiple myeloma who had one to three previous treatments were randomly assigned (1:1) using a blocked randomisation scheme (block size of four) to receive carfilzomib with dexamethasone (carfilzomib group) or bortezomib with dexamethasone (bortezomib group). Randomisation was stratified by previous proteasome inhibitor therapy, previous lines of treatment, International Staging System stage, and planned route of bortezomib administration if randomly assigned to bortezomib with dexamethasone. Patients received treatment until progression with carfilzomib (20 mg/m2 on days 1 and 2 of cycle 1; 56 mg/m2 thereafter; 30 min intravenous infusion) and dexamethasone (20 mg oral or intravenous infusion) or bortezomib (1·3 mg/m2; intravenous bolus or subcutaneous injection) and dexamethasone (20 mg oral or intravenous infusion). The primary endpoint was progression-free survival in the intention-to-treat population. All participants who received at least one dose of study drug were included in the safety analyses. The study is ongoing but not enrolling participants; results for the interim analysis of the primary endpoint are presented. The trial is registered at ClinicalTrials.gov, number NCT01568866. Findings: Between June 20, 2012, and June 30, 2014, 929 patients were randomly assigned (464 to the carfilzomib group; 465 to the bortezomib group). Median follow-up was 11·9 months (IQR 9·3-16·1) in the carfilzomib group and 11·1 months (8·2-14·3) in the bortezomib group. Median progression-free survival was 18·7 months (95% CI 15·6-not estimable) in the carfilzomib group versus 9·4 months (8·4-10·4) in the bortezomib group at a preplanned interim analysis (hazard ratio [HR] 0·53 [95% CI 0·44-0·65]; p<0·0001). On-study death due to adverse events occurred in 18 (4%) of 464 patients in the carfilzomib group and in 16 (3%) of 465 patients in the bortezomib group. Serious adverse events were reported in 224 (48%) of 463 patients in the carfilzomib group and in 162 (36%) of 456 patients in the bortezomib group. The most frequent grade 3 or higher adverse events were anaemia (67 [14%] of 463 patients in the carfilzomib group vs 45 [10%] of 456 patients in the bortezomib group), hypertension (41 [9%] vs 12 [3%]), thrombocytopenia (39 [8%] vs 43 [9%]), and pneumonia (32 [7%] vs 36 [8%]). Interpretation: For patients with relapsed or refractory multiple myeloma, carfilzomib with dexamethasone could be considered in cases in which bortezomib with dexamethasone is a potential treatment option. Funding: Onyx Pharmaceuticals, Inc., an Amgen subsidiary

From Versailles to Locarno : Keys to Polish foreign policy, 1919-25 / Anna M. Cienciala and Titus Komarnicki

xvii, 384 p. : maps ; 24 cm. Includes index. Bibliography: p. 347-364

Distribution of surface thrusts on Awocado fruit at the constant load value

W przeprowadzonych badaniach zaprezentowano wyniki pomiarów nacisków powierzchniowych awokado odmiany Fuerte w teście ściskania promieniowego pomiędzy płaskimi płytami przy stałej wartości obciążenia z uwzględnieniem czynnika czasu. Test przeprowadzono przy wykorzystaniu maszyny wytrzymałościowej Instron 5566. Na dolnej płycie pod ściskanym owocem Awocado umieszczony został czujnik systemu Tekscan o numerze 5076. Pozwoliło ta na ciągłą obserwację warstwic nacisków powierzchniowych na powierzchni styku oraz wyznaczenie rozkładu nacisków powierzchniowych pomiędzy awokado z płytą dolną maszyny wytrzymałościowej. Wyznaczono warstwice i rozkłady nacisków powierzchniowych w różanych etapach testu pełzania. Wykazano, że maksymalne i średnie wartości nacisków powierzchniowych ulegają wyraźnemu zmniejszeniu w trakcie całego testu. Rozkład nacisków powierzchniowych ma kształt typowy dla zagadnień kontaktowych w sprężystym zakresie odkształceń, gdzie maksymalne wartości znajdują się w centralnej strefie styku i mają rozkład zbliżony do krzywej parzystej. Pod koniec testu nastąpiło tylko nieznaczne wyrównanie rozkładu nacisków na powierzchni styku Awocado z elementem roboczym maszyny wytrzymałościowej.In the tests, which were carried out, results of measurements of surface thrusts of Awocado Fuerte cultivar in the radial compression test between flat panels at the constant load value including time factor were presented. The test was carried out with the use of Instron 5566 testing machine. On the bottom panel, under the compressed Awocado fruit a sensor of Tekscan system number 5076 was placed. It allowed a constant observation of contour lines of surface thrusts on the contact surface and determination of distribution of surface thrusts between Awocado with a bottom panel of the testing machine. Contour layers and distribution of the surface thrusts in different stages of creep test were determined. It was proved that the maximum and average values of the surface thrusts are subject to minimum changes during the whole test. Distribution of surface thrusts has a shape typical for contact issues in a spring scope of deformation, where maximum values are in the central zone of contact and have distribution similar to the even number curve. At the end of the test, distribution of thrusts on the contact surface of Awocado with a working element of the testing machine took place at the end of the test