Abstract
Cell-based therapy approaches have been shown to improve allogeneic hematopoietic cell transplantation (AHCT) outcome by reducing its severe toxic side effects, including graft rejection, acute and chronic graft-versus-host disease (GvHD) or delayed/ impaired immune reconstitution. Here, we discuss the use of intravenous apoptotic leukocyte infusion to improve AHCT outcome. In experimental AHCT models, we demonstrated that intravenous apoptotic leukocyte infusion, simultaneously to allogeneic bone marrow grafts, favors hematopoietic engraftment, prevents allo-immunization and delays acute GvHD onset. Here, we review the different mechanisms and the potential beneficial effects associated with the immunomodulatory properties of apoptotic cells in the AHCT setting.
Highlights
Cell based-therapy is a dynamic area of research that has made significant advances in recent times
After a brief description of the immune mechanisms involved in graft rejection and in acute graft-versus-host disease (GvHD), we will discuss the potential improvements that can be provided by intravenous apoptotic cell infusion
Despite significant improvements over the past decades performed in transplantation practice and patient care that significantly have been reducing patient mortality [8], GvHD still occurs at higher rate and remains the most life-threatening complication after allogeneic hematopoietic cell transplantation (AHCT)
Summary
Cell based-therapy is a dynamic area of research that has made significant advances in recent times. Among the different advances in AHCT [10], we will focus on 3 that support the use of intravenous apoptotic leukocyte infusion These advances are the following: successful transplantation from human leukocyte antigen (HLA)-mismatched and unrelated donors [10], successful cord blood transplantation [11], especially in adult patients [12,13,14,15,16] and introduction of the so-called reduced-intensity conditioning regimens (RIC) [17] (for a definition of RIC, please refer to [18]). The main complications include acute and chronic graft-versus-host disease (GvHD), prolonged immune deficiency due to delayed/impaired immune reconstitution or to graft rejection/failure This immunodeficient state –aggravated by the administration of non specific immunosuppressive drugs– exposes patients to life-threatening opportunistic infections.
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