Latest documents http://publikationen.ub.uni-frankfurt.de/index/index/ Tue, 18 Dec 2012 12:47:32 +0100 Tue, 18 Dec 2012 12:47:32 +0100 http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/27825 Background: Reconstitution of cytomegalovirus-specific CD3+CD8+ T cells (CMV-CTLs) after allogeneic hematopoietic stem cell transplantation (HSCT) is necessary to bring cytomegalovirus (CMV) reactivation under control. However, the parameters determining protective CMV-CTL reconstitution remain unclear to date. Design and Methods: In a prospective tri-center study, CMV-CTL reconstitution was analyzed in the peripheral blood from 278 patients during the year following HSCT using 7 commercially available tetrameric HLA-CMV epitope complexes. All patients included could be monitored with at least CMV-specific tetramer. Results: CMV-CTL reconstitution was detected in 198 patients (71%) after allogeneic HSCT. Most importantly, reconstitution with 1 CMV-CTL per µl blood between day +50 and day +75 post-HSCT discriminated between patients with and without CMV reactivation in the R+/D+ patient group, independent of the CMV-epitope recognized. In addition, CMV-CTLs expanded more daramtaically in patients experiencing only one CMV-reactivation than those without or those with multiple CMV reactivations. Monitoring using at least 2 tetramers was possible in 63% (n = 176) of the patients. The combinations of particular HLA molecules influenced the numbers of CMV-CTLs detected. The highest CMV-CTL count obtained for an individual tetramer also changed over time in 11% of these patients (n = 19) resulting in higher levels of HLA-B*0801 (IE-1) recognizing CMV-CTLs in 14 patients. Conclusions: Our results indicate that 1 CMV-CTL per µl blood between day +50 to +75 marks the beginning of an immune response against CMV in the R+/D+ group. Detection of CMV-CTL expansion thereafter indicates successful resolution of the CMV reactivation. Thus, sequential monitoring of CMV-CTL reconstitution can be used to predict patients at risk for recurrent CMV reactivation. Sylvia Borchers; Melanie Bremm; Thomas Lehrnbecher; Elke Dammann; Brigitte Pabst; Benno Wölk; Ruth Esser; Meral Yildiz; Matthias Eder; Michael Stadler; Peter Bader; Hans Martin; Andrea Jarisch; Gisbert Schneider; Thomas Klingebiel; Arnold Ganser; Eva Maria Mischak-Weissinger; Ulrike Köhl article http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/27825 Tue, 18 Dec 2012 12:47:32 +0100 http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/22676 Severe acute graft versus host disease (GvHD) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation. Human mesenchymal stromal cells (MSCs) play an important role in endogenous tissue repair and possess strong immune-modulatory properties making them a promising tool for the treatment of steroid-refractory GvHD. To date, a few reports exist on the use of MSCs in treatment of GvHD in children indicating that children tend to respond better than adults, albeit with heterogeneous results. We here present a review of the literature and the clinical course of two instructive pediatric patients with acute steroid-refractory GvHD after haploidentical stem cell transplantation, which exemplify the beneficial effects of third-party transplanted MSCs in treatment of acute steroid-refractory GvHD. Moreover, we provide a meta-analysis of clinical studies addressing the outcome of patients with steroid-refractory GvHD and treatment with MSCs in adults and in children (n = 183; 122 adults, 61 children). Our meta-analysis demonstrates that the overall response-rate is high (73.8%) and confirms, for the first time, that children indeed respond better to treatment of GvHD with MSCs than adults (complete response 57.4% vs. 45.1%, respectively). These data emphasize the significance of this therapeutic approach especially in children and indicate that future prospective studies are needed to assess the reasons for the observed differential response-rates in pediatric and adult patients. Additional file 1: MSCs expansion and release criteria.his file contains a detailed description of the MSCs expansion and release criteria for Case A and Case B. Caroline M. Wernicke; Thomas G. P. Grunewald; Hendrik Juenger; Selim Kuçi; Zyrafete Kuci; Ulrike Köhl; Ingo Mueller; Michaela Döring; Christina Peters; Anita Lawitschka; Hans-Jochem Kolb; Peter Bader; Stefan Burdach; Irene Teichert- von Lüttichau article http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/22676 Fri, 09 Sep 2011 13:31:01 +0200