British journal of haematology
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Randomized Controlled Trial Multicenter Study
Single versus tandem high-dose melphalan followed by autologous blood stem cell transplantation in multiple myeloma: long-term results from the phase III GMMG-HD2 trial.
The prospective, randomized phase III trial GMMG-HD2 aimed at demonstrating non-inferiority of single (Arm A) versus tandem (Arm B) high-dose melphalan followed by autologous transplantation (HDM/ASCT) with regard to 2-year event-free survival (EFS) in newly-diagnosed multiple myeloma (MM) and included 358 evaluable patients [Intention-to-treat population, (ITT), single/tandem HDM/ASCT: n = 177/181]. After a median follow-up of more than 11 years, non-inferiority of single versus tandem HDM/ASCT was demonstrated using the planned non-inferiority threshold of 15% of the 2-year EFS rate. Neither EFS (P = 0·53) nor overall survival (OS) (P = 0·33) differences were observed in the ITT population. ⋯ Ten-year OS for the entire ITT was 34% (95% confidence interval: 29-40%). OS after first relapse was significantly shortened in the tandem arm (P = 0·04). In this study single HDM/ASCT was non-inferior to tandem HDM/ASCT in MM.
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Cilengitide (CLG) is an inhibitor of both αv β3 and αv β5 integrins, with a defined anti-tumour effect in glioblastoma. Pre-clinical studies demonstrate its ability to restrain the bone resorbing property of metastatic osteotropic tumours and we have previously shown that the disablement of αv β3 in multiple myeloma (MM) plasma cells results in exhaustion of their in vitro osteoclast (OC)-like activity on bone substrate. Here, we investigated the effect of CLG on this functional property of MM cells. ⋯ Ultrastructural microscopy was used to evaluate the morphological changes in MM cells due to the effect of CLG on cell adhesion. The data from our study demonstrate that CLG restrains the bone resorbing function of MM cells by disabling their adhesion properties. Further investigations in pre-clinical studies of osteotropic tumours are warranted.
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Hellmut Hartert was the first person to exploit the viscoelastic properties of clotting blood to measure blood coagulation in 1948. Since then, the technology has improved, allowing these analyses to be performed as point-of-care tests with immediately-available results. The addition of several activators and inhibitors to the original assay creates a panel of tests able to quantify the different aspects of blood clotting that can rival conventional laboratory assays. ⋯ Viscoelastic analyses of blood coagulation are mainly used to guide haemostatic therapy in bleeding patients and have proven superior to standard clotting tests in some circumstances. There is potential to extend their use to other areas, such as drug monitoring, and diagnosis and management of congenital bleeding disorders. The forthcoming cartridge-based assays are expected to improve the reliability and usability of viscoelastic assays of blood coagulation but high quality clinical trials remain urgently needed to determine their exact place, benefit and cost effectiveness.