Narrative Review of Preparative Regimens Predictive of Mixed Chimerism After HLA-Mismatched Hematopoietic Stem Cell Transplantation: A Starting Point for Combined Solid Organ and Stem Cell Transplantation.

Transient or permanent mixed hematopoietic chimerism (MC) is associated with immunologic tolerance in combined solid organ and hematopoietic stem cell transplantation. This tolerance allows for the reduction or sometimes even suspension of systemic immunosuppression without graft rejection, with clear benefits regarding the side effects associated with lifelong immunosuppression. However, studies to date have included only living, HLA-matched donors to reduce the risk of graft-versus-host disease (GvHD), whereas the degree of HLA incompatibility between deceased donors and recipients is typically higher. Here we present a narrative review aimed at identifying the conditioning regimens predictive of MC in hematologic patients who have received an HLA-mismatched transplant, to provide some information on immunotolerance for future combined solid organ and stem cell transplantation in an HLA-mismatched setting. Among a total of 90 identified studies, 20 contained some information on MC, with a reported percentage of 2% to 100% of patients; 1186 patients were described in these 20 articles, with a median of 40 (range, 12 to 265) per study. When examining the conditioning regimens associated with MC ≥20% and GvHD <25% (n = 5), it was observed that 4 out of 5 studies contained antithymocyte globulin. The data suggest the importance of T lymphocyte depletion for achieving MC, associated with a low incidence of acute GvHD in hematopoietic stem cell transplantation from HLA-mismatched donors. Although additional work is needed, particularly on the ideal stem cell dose (ie, CD34+ and CD3+ cells), this information could be translated into the field of solid organ transplantation (SOT) to design a potential combined solid organ-stem cell transplantation protocol aimed at achieving MC for immune tolerance. The present work supports a translational perspective in the setting of SOT, where long-term immune tolerance is a major goal.