Multidonor bone marrow transplantation improves donor engraftment and increases the graft versus tumor effect while decreasing graft-versus-host disease

Abstract

In partially matched donor transplantation, mandatory T-cell depletion (TCD) increases the risks of rejection/graft failure, relapse, and post-transplant infections. A multi-donor approach was offered to resolve some of these drawbacks. This hypothesis was previously tested in a TCD fully mismatched murine model. However, the effect of multi-donor transplantation (MDT) on graft-versus-host disease (GVHD) and graft versus tumor (GVT) effect were never tested. To assess the safety and efficacy of MDT, we used it in non-TCD transplantation and murine breast carcinoma model. We found that when transplanting non-TCD MDT composed by C57Bl/6 and C3H cells into BALB/c, a consistent trichimerism is established, dominated by C57Bl/6 cells. Following MDT the study animals experienced reduced GVHD compare with those transplanted from C57Bl/6 alone, while the GVT effect was superior. We conclude that MDT may serve as a technique that suppresses GVHD while maintaining the GVT effect.