Transplant Evidence Alert

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A novel MSC-based immune induction strategy for ABO-incompatible liver transplantation: a phase I/II randomized, open-label, controlled trial

Stem Cell Res Ther. 2021 Apr 16;12(1):244 doi: 10.1186/s13287-021-02246-4.
Abstract
BACKGROUND:

ABO-incompatible liver transplantation (ABO-i LT) has become a rescue therapeutic option for patients with severe hepatic failure. Although the use of rituximab greatly reduces the morbidity of antibody-mediated rejection (AMR), severe adverse effects, such as infection and biliary complications, still seriously threaten the survival of transplant recipients. The aim of this study was to evaluate the safety and feasibility of using mesenchymal stem cells (MSCs) to replace rituximab in ABO-i LT.

METHODS:

Twenty-two patients with severe hepatic failure undergoing ABO-i LT were enrolled and randomly divided into two groups: the MSC group and the rituximab group. The safety of the application of MSCs and the incidence of allograft rejection, including antibody-mediated rejection (AMR) and acute cellular rejection (ACR), were evaluated in both groups at the 2-year follow-up period as primary endpoints. Recipients and graft survival and other postoperative complications were compared as secondary endpoints.

RESULTS:

No severe MSC-related adverse events were observed during the trial. MSC treatment yielded comparable, if not better, results than rituximab at decreasing the incidence of acute rejection (9.1% vs 27.3%). Inspiringly, compared to those in the rituximab group, the rates of biliary complications (0% vs 45.5%) and infection (9.1% vs 81.8%) were significantly decreased in the MSC group. In addition, there were no significant differences in 2-year graft and recipient survival between the two groups (81.8% vs 72.7%).

CONCLUSIONS:

Our data show that MSC transfusion is comparable to rituximab treatment for AMR prophylaxis following ABO-i LT. Additionally, the results indicate that MSCs are more beneficial to the prevention of infection and biliary complications and may be introduced as a novel immunosuppressive approach for ABO-i LT.

TRIAL REGISTRATION:

Trial registration: chictr.org.cn , ChiCTR2000037732. Registered 31 August 2020- Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=57074 .

CET Conclusion
Reviewer: Mr John O'Callaghan, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion: This is a very interesting RCT in ABO incompatible liver transplantation. This high risk subgroup of liver transplantation may be required for patients in desperate need of a liver and comes with high risks of rejection, infection and hepatic artery thrombosis. In this study, the control drug for immune induction was rituximab and this was compared to mesenchymal stem cells (MSC) as the study intervention. The trial is randomised, but the method of randomisation is not fully described so we cannot be sure it was free from bias. Also, the study was open-label and this is another potential avenue for bias. The primary endpoint was the tolerability and safety of multidose MSC administration in this population and the therapy appears to be well tolerated from the results of this study. The trial is too small to be powered to assess the secondary outcomes fully; despite an apparently large reduction in acute rejection, it is not statistically significant. There was, however, a significant reduction in sepsis episodes with MSC compared to Rituximab, and also a significant reduction in biliary complications. These results need to be viewed in the context of an unblinded trial. This study does however provide an informative stepping stone towards a larger RCT to properly assess the comparative effects of MSC in ABO incompatible liver transplantation, and the authors have such a trial registered (ChiCTR2000037732).
Methodological quality
Jadad score 2
Allocation concealment NO
Data analysis INTENTION TO TREAT
Study Details
Aims: The aim of this study was to assess the feasibility and safety of using mesenchymal stem cells (MSCs) as a replacement for rituximab in ABO-incompatible liver transplantation (ABO-i LT).
Interventions: Participants were randomised to either the rituximab group or the MSC group.
Participants: 22 patients receiving ABO-incompatible liver transplantation.
Outcomes: Primary outcomes included the assessment of MSC-related adverse events, incidence of antibody-mediated rejection (AMR) and acute cellular rejection (ACR). The secondary outcomes included graft survival and recipient survival, and the incidence of posttransplant complications (including biliary complications and specific infections).
Follow Up: 2 years
Metadata
Funding: Non-industry funding
Publication type: Randomized Controlled Trial, Randomised Controlled Trial
Trial registration: ChiCTR2000037732
Organ: Liver
Language: English
Author email: zhangq27@mail.sysu.edu.cn
MeSH terms: ABO Blood-Group System; Graft Rejection; Graft Survival; Humans; Liver Transplantation; Rituximab; Treatment Outcome; 0 (ABO Blood-Group System); 4F4X42SYQ6 (Rituximab)