Immune reconstitution after allogeneic stem cell transplantation with reduced-intensity conditioning regimens

Reduced-intensity conditioning (RIC) regimens have been increasingly used as an alternative to conventional myeloablative conditioning (MAC) regimens for elderly patients, for patients medically infirm to qualify for conventional allogeneic stem cell transplantation (SCT), and for disorders in which traditional MAC-SCT are associated with high rates of non-relapse mortality. One of the theoretical advantages of RIC-SCT is that it might lend to better immune reconstitution after transplantation due to less damage of the thymus, allowing regeneration of naive T cells derived from prethymic donor stem cells, and due to the proliferation of immunologically competent host T cells that survive the conditioning regimen. Although limited, studies comparing immune recovery following RIC and MAC-SCT have been insightful. One of the main difficulties of these studies is the current spectrum of RIC protocols, which vary considerably in myeloablative and immunosuppressive potential, resulting in apparently contradictory findings. In spite of this, most reports have shown significant quantitative and/or qualitative differences in T- and B-cell reconstitution after RIC-SCT in comparison with conventional SCT. This paper will review current knowledge of immune reconstitution following RIC-SCT.