Combination of Total Lymphoid Irradiation, Low-Dose IVIG and ATG as Rescue Therapy for Highly Sensitized and Antibody-Mediated Rejection Renal Transplant Recipients.

UNLABELLED: Background: It is now clear that antibody- mediated rejection (AMR) is a major cause of graft failure. To avoid AMR, transplantation is preferably performed in non- or low-sensitized patients. For patients with pre-existing HLA antibodies due to pre-transplant sensitization or those with de novo HLA antibodies due to transplantation, elimination or reduction of HLA antibodies becomes critical to prevent AMR. Materials and Methods: In this clinical trial, we test the efficacy of a combination therapy of total lymphoid irradiation (TLI), low- dose intravenous immunoglobulin (IVIG), and anti-thymocyte globulin (ATG) with or without plasmapheresis (PP) in treating patients with HLA antibodies. Thirteen HLA antibody positive patients receiving renal transplants during 2009-2011 were enrolled in this study. Two cases with pre-existing HLA antibodies received combined therapy of TLI, PP, low-dose IVIG, and ATG induction. Eleven cases with de novo HLA antibodies and biopsy-proven AMR received TLI, low-dose IVIG, and ATG with or without PP.

RESULTS: Two sensitized patients with pre-existing HLA antibodies were successfully desensitized and able to accept renal transplantation without an observable AMR episode in 12 months of post-transplant follow-up. In 11 AMR cases with de novo HLA antibodies, only one patient failed to respond to the therapy and lost the allograft. In the other ten cases, the follow-up biopsies at one year post transplant showed no evidence of rejection and the patients had stable renal function. B cell proliferation was persistently inhibited in both desensitization and AMR patients.

CONCLUSIONS: Combined therapy of TLI, PP, low-dose IVIG, and ATG is an effective therapeutic measure to reduce the level of HLA antibodies and therefore to desensitize recipients pre-transplant and to reverse AMR post transplant. The potential mechanism of the therapy involves inhibition of B cell proliferation.