Background: We investigated the efficacy and safety of tandem high-dose methotrexate (HD-MTX) induction followed by high-dose busulfan/thiotepa (HD-BuTT) with autologous peripheral blood stem-cell ...transplantation (aPBSCT) and response-adapted whole-brain radiation therapy (WBRT) in patients with newly diagnosed primary central nervous system lymphoma. Patients and methods: Twenty-three patients were treated with HD-MTX on days 1 and 10. In case of at least a partial remission (PR), HD-BuTT followed by aPBSCT was given. Patients without response to induction or without complete remission (CR) after HD-BuTT received WBRT. Results: Sixteen patients received HD-MTX and HD-BuTT achieving a CR/PR rate of 69%/13%. CR/PR rates for all patients (n = 23) were 70%/13%. There were three deaths during therapy. With longer follow-up three neurotoxic deaths occurred in irradiated patients (n = 9), while no persistent neurotoxicity was seen after HD-BuTT without subsequent WBRT. At a median follow-up of 15 months (range 1–69) median event-free survival (EFS) and overall survival (OS) for all patients were 17 and 20 months (Kaplan–Meier), after HD-BuTT 27 months and ‘not reached’, respectively. Estimated 2-year EFS and OS were 45% and 48% for all patients versus 56% and 61% for the HD-BuTT group, respectively. Conclusion: MTX induction followed by HD-BuTT is an effective and very short time-on-treatment regimen. Median survival for patients treated with high-dose chemotherapy is not reached yet. The induction regimen needs optimisation. In this study WBRT was associated with a high incidence of severe neurotoxicity.
We previously reported the results of a phase II study for patients with newly diagnosed primary central nervous system lymphoma treated with autologous peripheral blood stem-cell transplantation ...(aPBSCT) and response-adapted whole-brain radiotherapy (WBRT). Now, we update the initial results.
From 1999 to 2004, 23 patients received high-dose methotrexate. In case of at least partial remission, high-dose busulfan/thiotepa (HD-BuTT) followed by aPBSCT was carried out. Patients refractory to induction or without complete remission after HD-BuTT received WBRT. Eight patients still alive in 2011 were contacted and Mini-Mental State Examination (MMSE) and the European Organisation for Research and Treatment of Cancer quality-of-life questionnaire (QLQ)-C30 were carried out.
Of eight patients still alive, median follow-up is 116.9 months. Only one of nine irradiated patients is still alive with a severe neurologic deficit. In seven of eight patients treated with HD-BuTT, health condition and quality of life are excellent. MMSE and QLQ-C30 showed remarkably good results in patients who did not receive WBRT. All of them have a Karnofsky score of 90%–100%.
Follow-up shows an overall survival of 35%. In six of seven patients where WBRT could be avoided, no long-term neurotoxicity has been observed and all patients have an excellent quality of life.
Invasive fungal infections (IFIs) are a primary cause of morbidity and mortality in patients with hematological malignancies. Establishing a definite diagnosis of IFI in immunocompromised patients is ...particularly challenging and time consuming, but delayed initiation of antifungal treatment increases mortality. The limited overall outcome has led to the strategy of initiating either ‘empirical’ or ‘preemptive’ antifungal therapy before the final diagnosis. However, diagnostic procedures have been vastly improved in recent years. Particularly noteworthy is the introduction of newer imaging techniques and non-culture methods, including antigen-based assays, metabolite detection and molecular detection of fungal DNA from body fluid samples. Though varying widely in cancer patients, the risk of IFI is highest in those with allogeneic stem cell transplantation and those with acute leukemia. The AGIHO presents recommendations for the diagnosis of IFIs with risk-adapted screening concepts for febrile episodes in patients with haemato-oncological disorders.
Wings of modern aircraft have to be designed to give optimal response with respect to loads, comfort and performance. An essential part of the wing development is thus a design process which can take ...all these aspects into consideration. In the “Adaptive Wing” work package of the CleanSky “Smart Fixed Wing Aircraft” project, a multi-fidelity wing design method using aeroelastic tailoring has been developed. In the article, the process is presented in detail. The approach is based on a parametric wing design approach. Both beam models and shell models are derived and optimized in separate optimization environments. Investigations of the use of unbalanced laminates in aeroelastic tailoring are presented, employing the optimization of lamination parameters. The applications are demonstrated on two aircraft configurations, a long range and a short range transport aircraft. Further developments presented in the article include the introduction of CFD-based aerodynamics in the tailoring process, and a process extension to assess the influence of aeroelastic tailoring on fatigue.
Low Gain Avalanche Detector (LGAD) technology has been used to design and construct prototypes of time-zero detector for experiments utilizing proton and pion beams with High Acceptance Di-Electron ...Spectrometer (HADES) at GSI Darmstadt, Germany. LGAD properties have been studied with proton beams at the COoler SYnchrotron facility in Jülich, Germany. We have demonstrated that systems based on a prototype LGAD operated at room temperature and equipped with leading-edge discriminators reach a time precision below 50 ps. The application in the HADES, experimental conditions, as well as the test results obtained with proton beams are presented.
Allogeneic haematopoietic stem cell transplantation (allo-SCT) may provide donor cytotoxic T cell-/NK cell-mediated disease control in patients with rhabdomyosarcoma (RMS). However, little is known ...about the prevalence of graft-vs-RMS effects and only a few case experiences have been reported.
We evaluated allo-SCT outcomes of 30 European Group for Blood and Marrow Transplantation (EBMT)-registered patients with advanced RMS regarding toxicity, progression-free survival (PFS) and overall survival (OS) after allo-SCT. Twenty patients were conditioned with reduced intensity and ten with high-dose chemotherapy. Twenty-three patients were transplanted with HLA-matched and seven with HLA-mismatched grafts. Three patients additionally received donor lymphocyte infusions (DLIs). Median follow-up was 9 months.
Three-year OS was 20% (s.e.±8%) with a median survival time of 12 months. Cumulative risk of progression was 67% (s.e.±10%) and 11% (s.e.±6%) for death of complications. Thirteen patients developed acute graft-vs-host disease (GvHD) and five developed chronic GvHD. Eighteen patients died of disease and four of complications. Eight patients survived in complete remission (CR) (median: 44 months). No patients with residual disease before allo-SCT were converted to CR.
The use of allo-SCT in patients with advanced RMS is currently experimental. In a subset of patients, it may constitute a valuable approach for consolidating CR, but this needs to be validated in prospective trials.
The purpose of this study was to identify thrombin-activatable fibrinolysis inhibitor (TAFI) in saliva and to investigate the correlation between TAFI levels in saliva and plasma. Subjects included ...were healthy adults without diseases or medication that could affect coagulation. Samples of stimulated saliva and blood samples were obtained from 33 subjects. Levels of TAFI in saliva and plasma were analysed. The association between levels of TAFI in saliva and plasma was calculated using linear regression. Low levels of TAFIa/TAFIai were found in most saliva samples but only one sample had levels that were above the lower limit of detection of the assay used. TAFI (proenzyme) was not found in saliva, so no correlations could be calculated. In this study there was no indication that there is TAFI present in secreted saliva. Either TAFIa/TAFIai in saliva were much lower than in plasma and under the detection limit of the assay used, or there was no TAFIa/TAFIai in the saliva tested.
For the exploration and validation of the integration of efficient propulsion concepts and new technologies for future large passenger aircraft, it is necessary to establish suitable design, ...evaluation and measurement tools. Therefore, as one major activity of the Large Passenger Aircraft (LPA) Platform 1 of the Clean Sky 2 initiative, the so-called Cross-Capability Demonstrator (XDC), has been set up to develop and demonstrate powerful numerical and experimental methods for aerodynamic, aeroacoustics, and aeroelastic simulation and measurement tasks. The paper will give an overview of the activities to be performed within the XDC and present some of the latest achievements related to this demonstrator.
In the field of laser driven particle acceleration, many experiments with plain foil targets have been performed to investigate ion acceleration mechanisms such as TNSA and BOA. A more complex target ...geometry, for which the front and rear surface can be structured in a deterministic way, will lead to a better understanding of e.g. the actual source size, laser contrast related effect to the coupling efficiency of laser energy into the target of specifically shaped target surfaces or means to reduce the particle beam divergence such as ballistic focusing. A promising technology to manufacture complex 3D freeform targets is the two-photon-polymerization. With resolutions better than 200 nm, it is possible to create small targets with microstructured surfaces. We implemented the combination of two-photon-polymerization and UV-lithography to facilitate the handling of such small structures.
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