Stem Cells Versus Donor Specific Transfusions for Tolerance Induction in Living Donor Renal Transplantation

Abstract

We undertook this study to define the role of stem cell transplantation (SCT) versus donor-specific transfusion (DST) in tolerance induction and sustenance in living donor renal transplantation (LDRT). In this prospective three-armed trial in LDRT with 13 patients each in demographically well-balanced groups, tolerance induction protocol (TIP) was used with SCT in group 1, DST in group 2, and no induction in group 3. Tolerance induction protocol consisted of SCT/DST under conditioning with bortezomib, methylprednisone, rituximab, and rabbit antithymocyte globulin. Transplantation was performed with prednisone in groups 1 and 2 and with triple immunosuppression in group 3, if lymphocyte/flow crossmatch was negative; and if donor-specific antibodies (DSAs) were absent in the first 2 groups. Posttransplant monitoring included serum creatinine (SCr), peripheral T-regulatory cells (pTregs)(127/CD4+/25), and DSA for groups 1 and 2; DSA was eliminated in group 3. Rescue IS was started with rise of SCr/DSA/ rejection. Tolerance induction protocol was safe. Over a mean follow-up of 2 years, no patient/graft was lost in groups 1 and 2. One patient of group 3 lost graft to noncompliance. Protocol biopsies were unremarkable. Rejections were noted in six patients of group 1, five of group 2, and seven of group 3. Donor-specific antibodies were elevated in three patients of both groups. Mean SCr of all groups was similar; however, pTregs were increased posttransplant in groups 1 and 2 versus group 3. Group 1 had sustained rise in pTregs. Stem cell transplantation and DST are useful for immunosuppression minimization in LDRT with sustained generation of pTregs with SCT.