TY  - JOUR
A1  - Salzmann-Manrique, Emilia
A1  - Bremm, Melanie
A1  - Huenecke, Sabine
A1  - Stech, Milena
A1  - Orth, Andreas
A1  - Eyrich, Matthias
A1  - Schulz, Ansgar
A1  - Esser, Ruth
A1  - Klingebiel, Thomas
A1  - Bader, Peter
A1  - Herrmann, Eva
A1  - Koehl, Ulrike
T1  - 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
JF  - frontiers in Immunology
N2  - 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.
KW  - immune reconstitution
KW  - allogeneic stem cell transplantation
KW  - CD34 selection
KW  - CD3/19 depletion
KW  - children
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227302
VL  - 9
ER  - 
TY  - JOUR
A1  - Dietl, Sebastian
A1  - Schwinn, Stefanie
A1  - Dietl, Susanne
A1  - Riedl, Simone
A1  - Deinlein, Frank
A1  - Rutkowski, Stefan
A1  - von Bueren, Andre O.
A1  - Krauss, Jürgen
A1  - Schweitzer, Tilmann
A1  - Vince, Giles H.
A1  - Picard, Daniel
A1  - Eyrich, Matthias
A1  - Rosenwald, Andreas
A1  - Ramaswamy, Vijay
A1  - Taylor, Michael D.
A1  - Remke, Marc
A1  - Monoranu, Camelia M.
A1  - Beilhack, Andreas
A1  - Schlegel, Paul G.
A1  - Wölfl, Matthias
T1  - MB3W1 is an orthotopic xenograft model for anaplastic medulloblastoma displaying cancer stem cell- and Group 3-properties
JF  - BMC Cancer
N2  - Background
Medulloblastoma is the most common malignant brain tumor in children and can be divided in different molecular subgroups. Patients whose tumor is classified as a Group 3 tumor have a dismal prognosis. However only very few tumor models are available for this subgroup.

Methods
We established a robust orthotopic xenograft model with a cell line derived from the malignant pleural effusions of a child suffering from a Group 3 medulloblastoma.

Results
Besides classical characteristics of this tumor subgroup, the cells display cancer stem cell characteristics including neurosphere formation, multilineage differentiation, CD133/CD15 expression, high ALDH-activity and high tumorigenicity in immunocompromised mice with xenografts exactly recapitulating the original tumor architecture.

Conclusions
This model using unmanipulated, human medulloblastoma cells will enable translational research, specifically focused on Group 3 medulloblastoma.
KW  - cancer stem cells
KW  - anaplastic medulloblastoma
KW  - group 3
KW  - orthotopic xenograft
KW  - animal model
KW  - brain tumor
KW  - children
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-145877
VL  - 16
IS  - 115
ER  -