Renal transplantationplus hematopoietic stem cell transplantation as Induction therapy: a single-center 10-year experience

Abstract

Objective To explore the efficacy of renal transplantation plus hematopoietic stem cell transplantation on inducing immune tolerance and summarize its long-term follow-up outcomes. Methods From 2009 to 2018, a total of 11 cases of living related donor kidney transplantation plus hematopoietic stem cell transplantation were performed. Two of them were HLA-matched and the remainder were mismatched for one HLA haplotype. The donor hematopoietic stem cells were mobilized using granulocyte colony-stimulating factor at 5 days pre-transplantation and collected at 1 day pre-operation. The recipients received total lymphoid irradiation for 3 days pre-transplantation and received anti-thymocyte globulin induction during transplantation. The donor hematopoietic stem cells were infused at 2, 4 and 6 postoperative day. Postoperative regulatory T cells, chimerism, B cell activating factor and mixed lymphocyte culture and other parameters were detected and long-term follow-up outcomes tracked. Results The immune tolerance-inducible recipients had a significant increase in activated Treg. One HLA-matched recipient achieved 30%-50% of chimerism and lost after 6 months. However, other recipients did not achieve mixed chimerism. The BAFF of recipient spiked sharply after transplantation. Mixed lymphocyte culture indicated that a donor-specific low response was induced. The recipients were followed up for 717 to 3612 days. The first recipient lost renal function and another ten recipients had stable renal function. None of the recipients had myelosuppression or graft-versus-host disease. Allograft biopsy confirmed only one case of mild acute rejection. The dose of immunosuppressive agents was lowered in 5 patients. Conclusions Hematopoietic stem cell transplantation for inducing tolerance is safe during renal transplantation. And chimerism is essential for inducing immune tolerance. Key words: Living donor; Kidney transplantation; Hematopoietic stem cell transplantation; Chimerism; Tolerance