The Effect of Sirolimus Based Regimen On Immune Reconstitution After Allogeneic Stem Cell Transplantation

Background: Reconstitution of the immune system following allogeneic stem-cell transplantation (allo-SCT) is a complex process that requires successful engraftment of the hematopoietic stem cell, as well as adequate thymic function. Although GVHD control, improvements in antibiotic spectra, and circumspection in the use of immunosuppressants have helped, too many patients still die of infections because of insufficient immunologic recovery. Sirolimus has been used alone and in combination with calcineurin inhibitors for prevention of allograft rejection after solid organ transplantation. In the field of hematopoietic stem cell transplantation, the combination of sirolimus and tacrolimus has also resulted in a low incidence of acute GVHD and reduced transplant-related toxicity.

Methods: We evaluated the immune recovery status of 24 patients who received the combination of sirolimus and tacrolimus as a GvHD prophylaxis compared to a historical control (n=21) using tacrolimus and methotrexate (MTX). They were conditioned with myeloablative regimens.

Results: The incidence of acute GVHD in patients with sirolimus based regimen was lower. And the incidence of CMV or EBV reactivation in the same group was higher. The recovery of CD4⁺ T cells and natural killer (NK) cells seemed to be more delayed in recipients with sirolimus based regimen compared to those in patients with tacrolimus and MTX at 1 month after transplantation (8.8 +/- 1.6 vs 14.9 +/- 5.8 for CD4⁺ T cells, 35.7 +/- 6.4 vs 53.4 +/- 19.6 for NK cells). However, there was no significant difference between in the recovery of CD4⁺T cells and NK cells at 3 months after transplantation. In the aspect of humoral immunity, there was a trend to be lower in immunoglobulin-A and Ig-M levels during 1 month and 3 months after transplantation in patients with sirolimus based regimen. This difference was overcome around post-transplant 6 months. And regulatory T cells (CD4+CD25+Foxp3+) seemed to be higher in patients with sirolimus based regimen.

Conclusion: The sirolimus based regimen is associated with well-controlled acute GVHD. Although the correlation between the increased risk of infection and delayed immune reconstitution was not confirmed, the regimen might be cause of increasing the risk of opportunistic infection. Therefore we need an effort of early tapering of immunosuppressants and a careful monitoring for opportunistic infections in patients received sirolimus based regimen.