scholarly journals Tissue immune profiles supporting response to mesenchymal stromal cell therapy in acute graft-versus-host disease—a gut feeling

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Caroline Gavin ◽  
Erik Boberg ◽  
Lena Von Bahr ◽  
Matteo Bottai ◽  
Anton Törnqvist Andrén ◽  
...  

AbstractAcute graft-versus-host disease (aGvHD), post-allogeneic hematopoietic stem cell transplantation, is associated with high mortality rates in patients not responding to standard line care with steroids. Adoptive mesenchymal stromal cell (MSC) therapy has been established in some countries as a second-line treatment.Limitations in our understanding as to MSC mode of action and what segregates patient responders from non-responders to MSC therapy remain. The principal aim of this study was to evaluate the immune cell profile in gut biopsies of patients diagnosed with aGvHD and establish differences in baseline cellular composition between responders and non-responders to subsequent MSC therapy.Our findings indicate that a pro-inflammatory immune profile within the gut at the point of MSC treatment may impede their therapeutic potential. These findings support the need for further validation in a larger cohort of patients and the development of improved biomarkers in predicting responsiveness to MSC therapy.

Stem Cells ◽  
2020 ◽  
Vol 38 (5) ◽  
pp. 698-711 ◽  
Author(s):  
Giada Dal Collo ◽  
Annalisa Adamo ◽  
Alessandro Gatti ◽  
Edoardo Tamellini ◽  
Riccardo Bazzoni ◽  
...  

2014 ◽  
Vol 20 (10) ◽  
pp. 1580-1585 ◽  
Author(s):  
Fermín Sánchez-Guijo ◽  
Teresa Caballero-Velázquez ◽  
Olga López-Villar ◽  
Alba Redondo ◽  
Rocío Parody ◽  
...  

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 613
Author(s):  
Nidhi Sharma ◽  
Qiuhong Zhao ◽  
Bin Ni ◽  
Patrick Elder ◽  
Marcin Puto ◽  
...  

Acute graft versus host disease (aGVHD) remains a leading cause of morbidity and mortality in allogeneic hematopoietic stem cell transplant (allo-HSCT). Tacrolimus (TAC), a calcineurin inhibitor that prevents T-cell activation, is commonly used as a GVHD prophylaxis. However, there is variability in the serum concentrations of TAC, and little is known on the impact of early TAC levels on aGVHD. We retrospectively analyzed 673 consecutive patients undergoing allo-HSCT at the Ohio State University between 2002 and 2016. Week 1 TAC was associated with a lower risk of aGVHD II–IV at TAC level ≥10.15 ng/mL (p = 0.03) compared to the lowest quartile. The cumulative incidence of relapse at 1, 3 and 5 years was 33%, 38% and 41%, respectively. TAC levels at week 2, ≥11.55 ng/mL, were associated with an increased risk of relapse (p = 0.01) compared to the lowest quartile. Subset analysis with acute myeloid leukemia and myelodysplastic syndrome patients showed significantly reduced aGVHD with TAC level ≥10.15 ng/mL at week 1 and a higher risk of relapse associated with week 2 TAC level ≥11.55 ng/mL (p = 0.02). Hence, achieving ≥10 ng/mL during the first week of HCT may mitigate the risk of aGVHD. However, levels (>11 ng/mL) beyond the first week may be associated with suppressed graft versus tumor effect and higher relapse.


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