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  - Bonig, Halvard
A1  - Kuçi, Zyrafete
A1  - Kuçi, Selim
A1  - Bakhtiar, Shahrzad
A1  - Basu, Oliver
A1  - Bug, Gesine
A1  - Dennis, Mike
A1  - Greil, Johann
A1  - Barta, Aniko
A1  - Kállay, Krisztián M.
A1  - Lang, Peter
A1  - Lucchini, Giovanna
A1  - Pol, Raj
A1  - Schulz, Ansgar
A1  - Sykora, Karl-Walter
A1  - Teichert von Luettichau, Irene
A1  - Herter-Sprie, Grit
A1  - Ashab Uddin, Mohammad
A1  - Jenkin, Phil
A1  - Alsultan, Abdulrahman
A1  - Buechner, Jochen
A1  - Stein, Jerry
A1  - Kelemen, Agnes
A1  - Jarisch, Andrea
A1  - Soerensen, Jan
A1  - Salzmann-Manrique, Emilia
A1  - Hutter, Martin
A1  - Schäfer, Richard
A1  - Seifried, Erhard
A1  - Paneesha, Shankara
A1  - Novitzky-Basso, Igor
A1  - Gefen, Aharon
A1  - Nevo, Neta
A1  - Beutel, Gernot
A1  - Schlegel, Paul-Gerhardt
A1  - Klingebiel, Thomas
A1  - Bader, Peter
T1  - Children and adults with Refractory acute Graft-versus-Host Disease respond to treatment with the Mesenchymal Stromal cell preparation “MSC-FFM”—Outcome report of 92 patients
JF  - Cells
N2  - (1) Background: Refractory acute graft-versus-host disease (R-aGvHD) remains a leading cause of death after allogeneic stem cell transplantation. Survival rates of 15% after four years are currently achieved; deaths are only in part due to aGvHD itself, but mostly due to adverse effects of R-aGvHD treatment with immunosuppressive agents as these predispose patients to opportunistic infections and loss of graft-versus-leukemia surveillance resulting in relapse. Mesenchymal stromal cells (MSC) from different tissues and those generated by various protocols have been proposed as a remedy for R-aGvHD but the enthusiasm raised by initial reports has not been ubiquitously reproduced. (2) Methods: We previously reported on a unique MSC product, which was generated from pooled bone marrow mononuclear cells of multiple third-party donors. The products showed dose-to-dose equipotency and greater immunosuppressive capacity than individually expanded MSCs from the same donors. This product, MSC-FFM, has entered clinical routine in Germany where it is licensed with a national hospital exemption authorization. We previously reported satisfying initial clinical outcomes, which we are now updating. The data were collected in our post-approval pharmacovigilance program, i.e., this is not a clinical study and the data is high-level and non-monitored. (3) Results: Follow-up for 92 recipients of MSC-FFM was reported, 88 with GvHD ≥°III, one-third only steroid-refractory and two-thirds therapy resistant (refractory to steroids plus ≥2 additional lines of treatment). A median of three doses of MSC-FFM was administered without apparent toxicity. Overall response rates were 82% and 81% at the first and last evaluation, respectively. At six months, the estimated overall survival was 64%, while the cumulative incidence of death from underlying disease was 3%. (4) Conclusions: MSC-FFM promises to be a safe and efficient treatment for severe R-aGvHD.
KW  - graft-versus host
KW  - transplantation
KW  - mesenchymal stromal cell
KW  - cell therapy
KW  - hospital exemption
KW  - steroid-resistant aGvHD
KW  - refractory aGvHD
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193878
SN  - 2073-4409
VL  - 8
IS  - 12
ER  -