Autologous bone marrow-derived mesenchymal stromal cell therapy with early tacrolimus withdrawal: The randomized prospective, single-center, open-label TRITON study.Reinders, M. E. J., et al.
American Journal of Transplantation 2021; 21(9): 3055-3065.
The aim of this post hoc analysis was to investigate the effect of mesenchymal stromal cell (MSC) therapy with early tacrolimus withdrawal in renal transplant patients.
Participants in the original trial were randomised to either MSC plus early tacrolimus withdrawal or to standard tacrolimus dose.
70 living donor kidney transplant recipients.
The primary outcome was quantitative assessment of interstitial fibrosis. The secondary outcomes were patient death, graft loss, acute rejection, renal function, adverse events, and immunological responses.
This is a good quality and fair sized randomised controlled trial in renal transplantation. Patients received alemtuzumab induction therapy and then were maintained on prednisolone and tacrolimus. In the study arm, patients also received autologous mesenchymal stem cell (MSC) infusions and then had tacrolimus minimisation and subsequent withdrawal. The intention was to see if fibrosis could be reduced through tacrolimus withdrawal, using MSCs to reduce the risk of rejection in this context. Randomisation was performed by an online system and is likely to be truly random, however the nature of the intervention means that the study was not easily blinded and there is the potential for bias. However, pathologists examining the biopsies were blinded to the allocation and used standardised scoring, which is an important strength of the study. Withdrawals and dropouts are adequately described and the statistical methods are appropriate. The analysis was however not by strict intention-to-treat; one in 12 patients allocated to the study arm had abnormal MSC growth and could not receive that intervention so were excluded from the analysis for example. There were 4 patients in the control arm who refused to have a follow up biopsy and so were also excluded. These seem small numbers, but in a small trial are significant. The overall fibrosis scores and progression of fibrosis was the same in both arms of the study. Renal function was similar and risk of acute rejection was similarly low between the study arms. There was a significantly higher number of Tregs in the MSC group. A post hoc analysis of 5-year outcomes is presented, but does not indicate any significant differences. The study was too small to identify any significant difference in graft or patient survival. In conclusion, the use of MSC was safe within this study and was not associated with increased risk of rejection when combined with tacrolimus withdrawal.
ClinicalTrials.gov - NCT02057965