TY  - JOUR
A1  - Wiegering, Verena
A1  - Andres, Oliver
A1  - Schlegel, Paul G.
A1  - Deinlein, Frank
A1  - Eyrich, Matthias
A1  - Sturm, Alexander
T1  - Hyperfibrinolysis and acquired factor XIII deficiency in newly diagnosed pediatric malignancies
JF  - Haematologica
N2  - No abstract available
KW  - factor XIII deficiency
KW  - leukemia
KW  - tumor
KW  - perioperative bleeding
KW  - coagulopathy
KW  - hyperfibrinolysis
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130569
VL  - 98
IS  - 8
ER  - 
TY  - JOUR
A1  - Bäuerlein, Carina A.
A1  - Riedel, Simone S.
A1  - Baker, Jeanette
A1  - Brede, Christian
A1  - Jordán Garrote, Ana-Laura
A1  - Chopra, Martin
A1  - Ritz, Miriam
A1  - Beilhack, Georg F.
A1  - Schulz, Stephan
A1  - Zeiser, Robert
A1  - Schlegel, Paul G.
A1  - Einsele, Hermann
A1  - Negrin, Robert S.
A1  - Beilhack, Andreas
T1  - A diagnostic window for the treatment of acute graft-versus-host disease prior to visible clinical symptoms in a murine model
JF  - BMC Medicine
N2  - Background

Acute graft-versus-host disease (aGVHD) poses a major limitation for broader therapeutic application of allogeneic hematopoietic cell transplantation (allo-HCT). Early diagnosis of aGVHD remains difficult and is based on clinical symptoms and histopathological evaluation of tissue biopsies. Thus, current aGVHD diagnosis is limited to patients with established disease manifestation. Therefore, for improved disease prevention it is important to develop predictive assays to identify patients at risk of developing aGVHD. Here we address whether insights into the timing of the aGVHD initiation and effector phases could allow for the detection of migrating alloreactive T cells before clinical aGVHD onset to permit for efficient therapeutic intervention.

Methods

Murine major histocompatibility complex (MHC) mismatched and minor histocompatibility antigen (miHAg) mismatched allo-HCT models were employed to assess the spatiotemporal distribution of donor T cells with flow cytometry and in vivo bioluminescence imaging (BLI). Daily flow cytometry analysis of peripheral blood mononuclear cells allowed us to identify migrating alloreactive T cells based on homing receptor expression profiles.

Results

We identified a time period of 2 weeks of massive alloreactive donor T cell migration in the blood after miHAg mismatch allo-HCT before clinical aGVHD symptoms appeared. Alloreactive T cells upregulated α4β7 integrin and P-selectin ligand during this migration phase. Consequently, targeted preemptive treatment with rapamycin, starting at the earliest detection time of alloreactive donor T cells in the peripheral blood, prevented lethal aGVHD.

Conclusions

Based on this data we propose a critical time frame prior to the onset of aGVHD symptoms to identify alloreactive T cells in the peripheral blood for timely and effective therapeutic intervention.
KW  - Allogeneic stem cell transplantation
KW  - Graft-versus-host disease
KW  - Minor histocompatibility antigen mismatch transplantation
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96797
UR  - http://www.biomedcentral.com/1741-7015/11/134
ER  - 
TY  - JOUR
A1  - Eyrich, Matthias
A1  - Rachor, Johannes
A1  - Schreiber, Susanne C.
A1  - Wölfl, Matthias
A1  - Schlegel, Paul G.
T1  - Dendritic cell vaccination in pediatric gliomas: lessons learnt and future perspectives
JF  - Frontiers in Pediatrics
N2  - Immunotherapy of malignant gliomas with autologous dendritic cells (DCs) in addition to surgery and radiochemotherapy has been a focus of intense research during the past decade. Since both children and adults are affected by this highly aggressive brain tumor, 10–15% of the several hundred vaccinated patients represent children, making pediatric glioma patients the largest uniform pediatric vaccination cohort so far. In general, DC vaccination in malignant gliomas has been shown to be safe and several studies with a non-vaccinated control group could clearly demonstrate a survival benefit for the vaccinated patients. Interestingly, children and adolescents below 21 years of age seem to benefit even more than adult patients. This review summarizes the findings of the 25 clinical trials published so far and gives a perspective how DC vaccination could be implemented as part of multimodal therapeutic strategies in the near future.
KW  - pediatrics
KW  - malignant glioma
KW  - DC vaccination
KW  - clinical trial
KW  - immunotherapy
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96937
ER  -