PURPOSE:

Vascularized Composite Allograft (VCA) transplantation is a clinical reality but limited by chronic immunosuppression and rejection. Current clinical tolerance protocols rely on recipient conditioning and donor cell mobilization that limits use to living donor transplants. We sought to design a clinically relevant protocol applicable to cadaveric organs by demonstrating stem cell engraftment using AMD3100 (Plerixafor) as a single-dose agent for stem cell mobilization in our existing canine VCA transplant model in both DLA-haploidentical, related and DLA-mismatched, unrelated canine donor-recipient pairs.

METHODS:

8 DLA-haploidentical, related canine recipients (Group I) and 4 DLA-mismatched, unrelated canine recipients (Group II) received conditioning with 350-450cGy TBI, AMD3100-mobilized donor stem cells+Bone Marrow transfusion and simultaneous VCA transplantation with a short course of immunosuppression (MMF: 56 days/CSP: 70 days [Sirolimus 28 days as third agent for Group II]). CD34+ hematopoietic progenitor cells were quantified by flow cytometry. Peripheral blood chimerism was evaluated by PCR weekly. VCA graft survival was followed clinically and histologically.

RESULTS:

All 12 canines tolerated the conditioning regimen and demonstrated stem cell engraftment and donor chimerism. Mean COBE apheresis count: 3.98×10^8 cells/kg and mean BM aspirate count: 1.56×10^8 cells/kg across both groups. 5 dogs were not followed long-term (>70 days) due to complications from pulmonary hemorrhage, intussusception or GVHD. Mean dog survival post-transplant was 228 days. Of the 7 long-term survival recipients; only 1 showed evidence of an acute rejection episode that was self-limited. 4 dogs demonstrated evidence of GVHD (skin, liver) and 1 dog was lost to pulmonary hemorrhage all while seemingly tolerant to the VCA.

CONCLUSION:

This study demonstrates proof of principle for AMD3100 as a single-dose stem cell mobilizing agent for a clinically relevant tolerance protocol in both DLA-haploidentical, related and DLA-mismatched, unrelated donor-recipient pairs. Use of AMD3100 led to stem cell engraftment in all animals transplanted with only 1 canine demonstrating an acute rejection episode post-transplant.

CITATION INFORMATION: Swearingen B., Graves S., Storb R., Mathes D. AMD3100 (Plerixafor) as a Single-Dose Stem Cell Mobilizing Agent in Vascularized Composite Tissue Allograft (VCA) Transplantation in a Canine Model Am J Transplant. 2017;17 (suppl 3).

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