Combination of Total Lymphoid Irradiation, Low-Dose IVIg and ATG as Rescue Therapy for Highly Sensitized and Antibody-mediated Rejection Renal Transplant Recipients.
Zhu D, Qi G, Tang Q, Li L, Yang C, Lin M, Wu B, Xu M, Cai J, Zhu T, Rong R.
Clinical Transplants 2014, Chapter 27
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-xisting 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.