scholarly journals Peripheral Blood Stem Cells for T Cell–Replete Nonmyeloablative Hematopoietic Transplants Using Post-Transplant Cyclophosphamide

2014 ◽  
Vol 20 (5) ◽  
pp. 598-599 ◽  
Author(s):  
Asad Bashey
Keyword(s):  
Stem Cells ◽  
T Cell ◽  
Peripheral Blood ◽  
Peripheral Blood Stem Cells ◽  
Post Transplant ◽  
Blood Stem Cells

Allograft Cell Content and GVHD Differ in Murine Recipients of AMD3100 Versus G-CSF Mobilized Peripheral Blood Stem Cells.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3108-3108
Author(s):  
A. Lundqvist ◽  
N. Hamoui ◽  
J. Andersson ◽  
M. Elshal ◽  
Y. Takahashi ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
T Cell ◽  
Murine Model ◽  
Peripheral Blood ◽  
Lower Percentage ◽  
Peripheral Blood Stem Cells ◽  
Hematopoietic Stem ◽  
Recipient Group ◽  
Blood Stem Cells

Abstract G-CSF is currently the preferred agent to mobilize peripheral blood stem cells (PBSC) for allogeneic hematopoietic cell transplantation. AMD3100, a selective antagonist of SDF-1, has recently proven to rapidly mobilize hematopoietic stem cells in both humans and mice. It is currently unknown whether GVHD will differ in recipients of T-cell replete allografts mobilized with AMD3100 versus G-CSF. Therefore, we investigated the effects of AMD3100 on GVHD in a murine model of PBSC transplantation in which Balb/c recipients received 15x106 splenocytes from allogeneic MHC matched B10.d2 mice following 950cGy of irradiation. Splenocytes from donor mice were harvested six hours after a single subcutaneous injection of AMD3100 (100μg). Controls consisted of Balb/c recipients of splenocytes harvested after five daily subcutaneous injections of G-CSF (10μg) or saline. In addition, one Balb/c cohort received splenocytes mobilized with the combination of G-CSF and AMD3100. Significantly higher numbers of stem cells (KLS cells; cKit+, lineage-, sca-1+) were mobilized after AMD3100 compared to saline controls (mean=32,300±3,900 vs. 14,700±4,900; p=0.02). The absolute number of KLS cells was significantly lower after AMD3100 mobilization compared to G-CSF (mean=52,400±8,600; p=0.03). No difference in number of KLS cells was observed in mice mobilized with AMD3100 and G-CSF compared to G-CSF alone. Splenocytes from G-CSF mobilized B10.d2 donors contained a significantly (p<0.01) lower percentage of T cells (15.9±3.1%) than AMD3100 mobilized donors (20.3±3.5%). The incidence of skin GVHD was higher in Balb/c recipients of AMD3100 mobilized splenocytes (19/20) compared to G-CSF mobilized splenocytes (5/18; p<0.01), while recipients of donors mobilized with the combination of G-CSF and AMD3100 had a slightly higher incidence of skin GVHD (9/20, p<0.01) compared to G-CSF alone. Using a cumulative clinical GVHD scoring system (maximum 9 points), the severity of GVHD was higher in mice receiving AMD3100 compared to mice receiving G-CSF (day +45 mean score=1.8 vs. 0.4 respectively; p<0.01) or G-CSF + AMD3100 (mean score=0.8; p=0.03) mobilized splenocytes. When the T cell dose was adjusted to equal numbers in all transplant groups, the difference in GVHD between cohorts was less pronounced; 8/8 (100%) in the AMD3100 recipient group compared to 4/9 (44%; p=0.03) in the G-CSF recipient group developed skin GVHD. Th1/Th2 serum cytokine profiles following mobilization were similar in all donor groups. Compared to G-CSF, AMD3100, given alone or in combination with G-CSF, mobilized comparable numbers of CD4/CD25+ regulatory T cells with similar MLR suppressive effects. In contrast, the percentage of memory T cells (CD62L-) was significantly increased in mice mobilized with G-CSF (89.1±3.0%) compared to AMD3100 (43.9±1.3%), potentially accounting for the lower incidence of GVHD in recipients of G-CSF mobilized PBSC. This murine model provides the first insight into differences in GVHD that may occur when allogeneic transplantation is performed using T-cell replete PBSC allografts mobilized with AMD3100. Whether the higher incidence of GVHD observed in recipients of AMD3100 mobilized PBSC will enhance graft vs. tumor effects in tumor bearing Balb/c recipients is currently under investigation.

The Study on Influence of T Cell Ratios Between Grafts to Recipients on Gvhd in HLA- Haploidentical Allogeneic Peripheral Blood Stem Cells Transplantation

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4621-4621
Author(s):  
Hui Liang ◽  
Xiao-hui Deng ◽  
Xia Weng
Keyword(s):  
Clinical Trial ◽  
Stem Cells ◽  
T Cells ◽  
T Cell ◽  
Peripheral Blood ◽  
Animal Experiment ◽  
Classical Method ◽  
Peripheral Blood Stem Cells ◽  
Blood Stem Cells ◽  
Stem Cells Transplantation

Abstract Objective To study the influence of T cell ratios between grafts to recipients on GVHD in HLA- haploidentical allogeneic peripheral blood stem cells transplantation ( PBSCT ). Methods: Animal experiment: We set up rat allo-BMT model. Male SD rats were transplanted with female Wistar rats.Recipient rats of experiment group were transplanted with the CD3+ T cells of female Wistar rats at different graft-receptor T cell ratios, 1:1 (group A1), 2:1 ( group A2), 4:1 ( group A3) respectively. Control group (group B) were infused with grafts consisting of 3×107 bone marrow cells by classical method. Observe the incidence and severity of GVHD of different groups. Clinical trial: 6 cases of HLA-haploidentical allogeneic PBSCT. 4 patients were transplantated with purified allo-CD34+ cells. Next day, adjusted graft-receptor T cell ratios to 2:1 by infusing donor CD3+ T cells. Another 2 patient were treated with classical allo-PBSCT. Results Animal experiment: The severity of GVHD in group A1, A2 were lighter compared with group A3,B. The difference is significant among group A1,A2 and A3. Clinical trial: An ultra-acute severe GVHD occurred in 2 patients who were transplanted with classical method. They died from interstitial pneumonia secondary to PBSCT. The remaining 4 cases only presented mild aGVHD.Among these 4 cases, 3 patients had DFS (disease free survival) over 3 years, 1 patient died from polyradiculitis on +155d. Conclusion: On the basis of our animal experiment, the appropriate graft-receptor T cell ratios would be 1:1 or 2:1. If we applied this ratio to clinical transplantation, especially to part HLA-related and HLA-haploidentical transplantation, we could obtained a better GVL effect and a lighter GVHD.

scholarly journals T cell depletion of allogeneic peripheral blood stem cells

1998 ◽  
Vol 21 (4) ◽  
pp. 429-430 ◽  
Author(s):  
M Starobinski ◽  
E Roosnek ◽  
G Hale ◽  
E Roux ◽  
C Helg ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cell ◽  
Peripheral Blood ◽  
Cell Depletion ◽  
Peripheral Blood Stem Cells ◽  
T Cell Depletion ◽  
Blood Stem Cells
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