February 5, 2014
The first patient in the ITN’s ACCEPTOR study (Post-transplant Cyclophosphamide) completed the combined hematopoietic stem cell (HSC) and kidney transplant procedure yesterday at Johns Hopkins Hospital.
The approach to solid organ transplant in the ACCEPTOR study aims to induce the stable presence of both host and donor immune systems simultaneously, called “mixed chimerism,” via HSC transplant. A chimeric immune system, even just temporarily, may create a more suitable environment for engraftment of the donor kidney and promote tolerance (as was demonstrated in an earlier ITN study). Mixed chimerism approaches for transplant tolerance are complicated by the possibility of graft-vs-host disease (GVHD) which arises from an immune attack by donor lymphocytes (from the HSC transplant) on normal recipient tissue. A key component of the ACCEPTOR study is high-dose cyclophosphamide, given on day 3 and day 4 post-transplant, to eliminate proliferating T cells from both donor and recipient while allowing other cyclophosphamide-resistant lymphocytes to re-populate and potentially facilitate allograft tolerance.
This is a very innovative yet aggressive therapeutic regimen that has demonstrated success in HSC transplant recipients with hematologic disorders, and the ACCEPTOR study will assess the safety of this regimen in a total of 6 kidney transplant recipients at Johns Hopkins Hospital.
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