Increased regulatory T cell graft content is associated with improved outcome in haematopoietic stem cell transplantation: a systematic review

Increased regulatory T cell graft content is associated with improved outcome in haematopoietic stem cell transplantation: a systematic review
GVHD is a major cause of morbidity and mortality in patients post hematopoietic stem cell transplant (HSCT). Previous studies have indicated that low amounts of regulatory T cells in the grafts were found in patients who developed GVHD. This article is a systematic review of studies which reported the regulatory T cell (Treg) composition of donated grafts to determine if the amount of Tregs in a graft influence clinical outcomes, specifically in regards to GVHD incidence and severity.
A systematic review was done using defined eligibility criteria, and involved both adult and paediatric data. The search was limited to articles published in 2000 and onward. Five reviewers were involved in determining eligible studies. Forty-eight references were identified, describing 14 independent studies and 987 participants.
Consistent reports were found throughout the identified studies. Significant improvement was found in overall survival associated with high Tregs in most studies, as well as significant reduction in acute GVHD incidence; however, no studies showed an effect of Treg number or ratios on the incidence of chronic GVHD. Only 2 studies were included in a meta-analysis for overall survival but high Tregs were associated with increased survival (p = 0.003).
The included studies were conducted at different centres with heterogeneous indications for transplant, recipient demographics and co-morbidities, sources of allografts, conditioning, Treg measurement method, and post-transplant management. Many of the studies included were small and likely under-powered, and there may be a risk of small study and publication bias.
This systematic review indicates a clear and consistent benefit to higher levels of regulatory T cells in allogeneic haematopoietic stem cell transplants. Improvement of Treg/T cell ratios for HSCT allografts could prove to be an effective measuring in decreasing the risk of acute GVHD. Further multi-centre, prospective trials with standardized methods of measuring Tregs are warranted.