Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall D1
BACKGROUND: Vascularized Composite Allograft (VCA) transplantation is a clinical reality but application is limited by toxicities of chronic immunosuppression and rejection. Current clinical tolerance protocols limit 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 for stem cell mobilization.
METHODS: 4 DLA-haploidentical related canine recipients [Group I] received conditioning with 350cGy TBI, AMD3100-mobilized donor stem cells and VCA transplantation with a short course of immunosuppression. 6 DLA-haploidentical related canine recipients [Group II] underwent identical conditioning plus an infusion of Bone Marrow (BM) harvested on the day of transplant. 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 dogs in the first group exhibited prolonged thrombocytopenia and 1 dog was euthanized secondary to this complication (POD 32). All 4 demonstrated initial stem cell engraftment. One dog had very poor initial engraftment and went on to reject the VCA on POD 146. Remaining 2 dogs remained tolerant to their VCA (POD 79; 101). The addition of BM eliminated the problems with prolonged thrombocytopenia. In Group II, 2 dogs were euthanized secondary to pneumonia (POD 12; 95) and 1 for liver dysfunction (POD 45). Currently 3 dogs are doing well with no evidence of GVHD or loss of the VCA transplant (POD 211; 92; 24).
CONCLUSION: This study demonstrates that a clinically relevant protocol using a single dose of AMD3100 and addition of a bone marrow aspirate combined with our non-myeloabative protocol can lead to tolerance the VCA across a significant genetic barrier.
CITATION INFORMATION: Swearingen B, Graves S, Storb R, Mathes D. A Clinically Relevant Protocol for Vascularized Composite Allotransplantation Using a Single Dose of AMD3100 for Stem Cell Mobilization. Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:Swearingen B, Graves S, Storb R, Mathes D. A Clinically Relevant Protocol for Vascularized Composite Allotransplantation Using a Single Dose of AMD3100 for Stem Cell Mobilization. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/a-clinically-relevant-protocol-for-vascularized-composite-allotransplantation-using-a-single-dose-of-amd3100-for-stem-cell-mobilization/. Accessed January 25, 2020.
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