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- Gerbitz, Armin, et al.
(author)
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Prevention of CMV/EBV reactivation by double-specific T cells in patients after allogeneic stem cell transplantation : results from the randomized phase I/IIa MULTIVIR-01 study
- 2023
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In: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 14
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Journal article (peer-reviewed)abstract
- IntroductionAllogeneic stem cell transplantation is used to cure hematologic malignancies or deficiencies of the hematopoietic system. It is associated with severe immunodeficiency of the host early after transplant and therefore early reactivation of latent herpesviruses such as CMV and EBV within the first 100 days are frequent. Small studies and case series indicated that application of herpes virus specific T cells can control and prevent disease in this patient population.MethodsWe report the results of a randomized controlled multi centre phase I/IIa study (MULTIVIR-01) using a newly developed T cell product with specificity for CMV and EBV derived from the allogeneic stem cell grafts used for transplantation. The study aimed at prevention and preemptive treatment of both viruses in patients after allogeneic stem cell transplantation targeting first infusion on day +30. Primary endpoints were acute transfusion reaction and acute-graft versus-host-disease after infusion of activated T cells.ResultsThirty-three patients were screened and 9 patients were treated with a total of 25 doses of the T cell product. We show that central manufacturing can be achieved successfully under study conditions and the product can be applied without major side effects. Overall survival, transplant related mortality, cumulative incidence of graft versus host disease and number of severe adverse events were not different between treatment and control groups. Expansion of CMV/EBV specific T cells was observed in a fraction of patients, but overall there was no difference in virus reactivation.DiscussionOur study results indicate peptide stimulated epitope specific T cells derived from stem cell grafts can be administered safely for prevention and preemptive treatment of reactivation without evidence for induction of acute graft versus host disease.Clinical trial registrationhttps://clinicaltrials.gov, identifier NCT02227641.
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| 3. |
- Rauch, Alexander, et al.
(author)
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Glucocorticoids suppress bone formation by attenuating osteoblast differentiation via the monomeric glucocorticoid receptor.
- 2010
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In: Cell metabolism. - : Elsevier BV. - 1932-7420 .- 1550-4131. ; 11:6, s. 517-31
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Journal article (peer-reviewed)abstract
- Development of osteoporosis severely complicates long-term glucocorticoid (GC) therapy. Using a Cre-transgenic mouse line, we now demonstrate that GCs are unable to repress bone formation in the absence of glucocorticoid receptor (GR) expression in osteoblasts as they become refractory to hormone-induced apoptosis, inhibition of proliferation, and differentiation. In contrast, GC treatment still reduces bone formation in mice carrying a mutation that only disrupts GR dimerization, resulting in bone loss in vivo, enhanced apoptosis, and suppressed differentiation in vitro. The inhibitory GC effects on osteoblasts can be explained by a mechanism involving suppression of cytokines, such as interleukin 11, via interaction of the monomeric GR with AP-1, but not NF-kappaB. Thus, GCs inhibit cytokines independent of GR dimerization and thereby attenuate osteoblast differentiation, which accounts, in part, for bone loss during GC therapy.
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| 4. |
- Silberzahn, Raphael, et al.
(author)
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Many analysts, one dataset : Making transparent how variations in analytical choices affect results
- 2018
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In: Advances in Methods and Practices in Psychological Science. - : Sage Publications. - 2515-2459 .- 2515-2467. ; 1:3, s. 337-356
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Journal article (peer-reviewed)abstract
- Twenty-nine teams involving 61 analysts used the same dataset to address the same research question: whether soccer referees are more likely to give red cards to dark skin toned players than light skin toned players. Analytic approaches varied widely across teams, and estimated effect sizes ranged from 0.89 to 2.93 in odds ratio units, with a median of 1.31. Twenty teams (69%) found a statistically significant positive effect and nine teams (31%) observed a non-significant relationship. Overall 29 differentanalyses used 21 unique combinations of covariates. We found that neither analysts' prior beliefs about the effect, nor their level of expertise, nor peer-reviewed quality of analysis readily explained variation in analysis outcomes. This suggests that significant variation in the results of analyses of complex data may be difficult to avoid, even by experts with honest intentions. Crowdsourcing data analysis, a strategy by which numerous research teams are recruited to simultaneously investigate the same research question, makes transparent how defensible, yet subjective analytic choices influence research results.
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