@article{SalzmannManriqueBremmHueneckeetal.2018,
  author    = {Salzmann-Manrique, Emilia and Bremm, Melanie and Huenecke, Sabine and Stech, Milena and Orth, Andreas and Eyrich, Matthias and Schulz, Ansgar and Esser, Ruth and Klingebiel, Thomas and Bader, Peter and Herrmann, Eva and Koehl, Ulrike},
  title     = {Joint Modeling of Immune Reconstitution Post Haploidentical Stem Cell Transplantation in Pediatric Patients With Acute Leukemia Comparing CD34(+)-Selected to CD3/CD19-Depleted Grafts in a Retrospective Multicenter Study},
  series = {frontiers in Immunology},
  volume    = {9},
  journal   = {frontiers in Immunology},
  doi       = {10.3389/fimmu.2018.01841},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227302},
  pages     = {1841, 1-12},
  year      = {2018},
  abstract  = {Rapid immune reconstitution (IR) following stem cell transplantation (SCT) is essential for a favorable outcome. The optimization of graft composition should not only enable a sufficient IR but also improve graft vs. leukemia/tumor effects, overcome infectious complications and, finally, improve patient survival. Especially in haploidentical SCT, the optimization of graft composition is controversial. Therefore, we analyzed the influence of graft manipulation on IR in 40 patients with acute leukemia in remission. We examined the cell recovery post haploidentical SCT in patients receiving a CD34(+)-selected or CD3/CD19-depleted graft, considering the applied conditioning regimen. We used joint model analysis for overall survival (OS) and analyzed the dynamics of age-adjusted leukocytes; lymphocytes; monocytes; CD3(+), CD3(+) CD4(+), and CD3(+) CD8(+) T cells; natural killer (NK) cells; and B cells over the course of time after SCT. Lymphocytes, NK cells, and B cells expanded more rapidly after SCT with CD34(+)-selected grafts (P = 0.036, P = 0.002, and P < 0.001, respectively). Contrarily, CD3(+) CD4(+) helper T cells recovered delayer in the CD34 selected group (P = 0.026). Furthermore, reduced intensity conditioning facilitated faster immune recovery of lymphocytes and T cells and their subsets (P < 0.001). However, the immune recovery for NK cells and B cells was comparable for patients who received reduced-intensity or full preparative regimens. Dynamics of all cell types had a significant influence on OS, which did not differ between patients receiving CD34(+)-selected and those receiving CD3/CD19-depleted grafts. In conclusion, cell reconstitution dynamics showed complex diversity with regard to the graft manufacturing procedure and conditioning regimen.},
  language  = {en}
}
@article{DixCzakaiSpringeretal.2016,
  author    = {Dix, Andreas and Czakai, Kristin and Springer, Jan and Fliesser, Mirjam and Bonin, Michael and Guthke, Reinhard and Schmitt, Anna L. and Einsele, Hermann and Linde, J{\"o}rg and L{\"o}ffler, J{\"u}rgen},
  title     = {Genome-Wide Expression Profiling Reveals S100B as Biomarker for Invasive Aspergillosis},
  series = {Frontiers in Microbiology},
  journal   = {Frontiers in Microbiology},
  number    = {7},
  doi       = {10.3389/fmicb.2016.00320},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-165386},
  pages     = {320},
  year      = {2016},
  abstract  = {Invasive aspergillosis (IA) is a devastating opportunistic infection and its treatment constitutes a considerable burden for the health care system. Immunocompromised patients are at an increased risk for IA, which is mainly caused by the species Aspergillus fumigatus. An early and reliable diagnosis is required to initiate the appropriate antifungal therapy. However, diagnostic sensitivity and accuracy still needs to be improved, which can be achieved at least partly by the definition of new biomarkers. Besides the direct detection of the pathogen by the current diagnostic methods, the analysis of the host response is a promising strategy toward this aim. Following this approach, we sought to identify new biomarkers for IA. For this purpose, we analyzed gene expression profiles of hematological patients and compared profiles of patients suffering from IA with non-IA patients. Based on microarray data, we applied a comprehensive feature selection using a random forest classifier. We identified the transcript coding for the S100 calcium-binding protein B (S100B) as a potential new biomarker for the diagnosis of IA. Considering the expression of this gene, we were able to classify samples from patients with IA with 82.3\% sensitivity and 74.6\% specificity. Moreover, we validated the expression of S100B in a real-time reverse transcription polymerase chain reaction (RT-PCR) assay and we also found a down-regulation of S100B in A. fumigatus stimulated DCs. An influence on the IL1B and CXCL1 downstream levels was demonstrated by this S100B knockdown. In conclusion, this study covers an effective feature selection revealing a key regulator of the human immune response during IA. S100B may represent an additional diagnostic marker that in combination with the established techniques may improve the accuracy of IA diagnosis.},
  language  = {en}
}
@article{FujiKappEinsele2013,
  author    = {Fuji, Shigeo and Kapp, Markus and Einsele, Hermann},
  title     = {Alloreactivity of virus-specific T cells: possible implication of graft-versus-host disease and graft-versus-leukemia effects},
  series = {Frontiers in Immunology},
  volume    = {4},
  journal   = {Frontiers in Immunology},
  number    = {330},
  doi       = {10.3389/fimmu.2013.00330},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-129260},
  year      = {2013},
  abstract  = {Immune reconstitution of functional virus-specific T cells after allogeneic hematopoietic stem cell transplantation (HSCT) has been intensively investigated. However, the possible role of crossreactivity of these virus-specific T cells against allogeneic targets is still unclear. Theoretically, as in the field of organ transplantation, virus-specific T cells possess crossreactivity potential after allogeneic HSCT. Such crossreactivity is assumed to play a role in graft-versus-host disease and graft-versus-leukemia effects. In this article, we aim to give a comprehensive overview of current understanding about crossreactivity of virus-specific T cells.},
  language  = {en}
}
@article{FujiKappEinsele2013,
  author    = {Fuji, Shigeo and Kapp, Markus and Einsele, Hermann},
  title     = {Monitoring of Pathogen-Specific T-Cell Immune Reconstitution after Allogeneic Hematopoietic Stem Cell Transplantation},
  series = {Frontiers in Immunology},
  volume    = {4},
  journal   = {Frontiers in Immunology},
  number    = {276},
  doi       = {10.3389/fimmu.2013.00276},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-129250},
  year      = {2013},
  abstract  = {The clinical outcome after allogeneic hematopoietic stem cell transplantation (HSCT) has been significantly improved during the last decades with regard to the reduction in organ failure, infection, and severe acute graft-versus-host disease. However, severe complications due to infectious diseases are still one of the major causes of morbidity and mortality after allogeneic HSCT, in particular in patients receiving haploidentical HSCT or cord blood transplant due to a slow and often incomplete immune reconstitution. In order to improve the immune control of pathogens without an increased risk of alloreactivity, adoptive immunotherapy using highly enriched pathogen-specificT cells offers a promising approach. In order to identify patients who are at high risk for infectious diseases, several monitoring assays have been developed with potential for the guidance of immunosuppressive drugs and adoptive immunotherapy in clinical practice. In this article, we aim to give a comprehensive overview regarding current developments of T-cell monitoring techniques focusing on T cells against viruses and fungi. In particular, we will focus on rather simple, fast, non-labor-intensive, cellular assays which could be integrated in routine clinical screening approaches.},
  language  = {en}
}