AMD3100 (Plerixafor) As A Single-Dose Stem Cell Mobilizing Agent In Vascularized Composite Tissue Allograft (VCA) Transplantation In A Canine Haploidentical Model
Bruce J. Swearingen, MD1, Scott S. Graves, PhD2, Rainer Storb, MD2, David W. Mathes, MD1.
1University of Colorado Anschutz Medical Campus, Aurora, CO, USA, 2Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
PURPOSE: Vascularized Composite Allograft (VCA) transplantation is a clinical reality but limited by toxicities of chronic immunosuppression and rejection. Current clinical tolerance protocols rely on recipient conditioning and donor cell mobilization limiting use to living donor transplants. We sought to design a clinically relevant protocol applicable to cadaveric organs. We modified our existing non-myeloablative stem cell canine VCA transplant model to use AMD3100 (Plerixafor) for stem cell mobilization.
METHODS: 5 DLA-haploidentical, related canine recipients received conditioning with 350cGy TBI, AMD3100-mobilized donor stem cells and VCA transplantation with a short course of immunosuppression (MMF: 84 days/CSP: 133 days; including taper). CD34+ hematopoietic progenitor cells were quantified via flow cytometry. Peripheral blood chimerism was evaluated by PCR techniques weekly. VCA graft survival was followed clinically and histologically.
RESULTS: All 5 canines tolerated the conditioning regimen. 4 were followed long-term. Stem cell engraftment and donor chimerism were seen in all dogs. Median COBE apheresis cell counts of 6.12x10^8 cells/kg and CD34+ cell count of 5.27x10^7 cells/kg were obtained. No acute rejection nor evidence of GVHD was seen. An unexpected finding of persistent thrombocytopenia resolved on loss of donor cell chimerism.
CONCLUSION: This study demonstrates proof of principle for AMD3100 as a single-dose stem cell mobilizing agent for a clinically relevant tolerance protocol. Use of AMD3100 led to stem cell engraftment in all animals transplanted with no evidence of acute rejection in the VCA. Current application of AMD3100 is limited by thrombocytopenia but we are currently modifying the protocol to address this issue.
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