In rat models of limb allograft transplantation, the combination of vascularized bone marrow transplantation (VBMT) with both Csa and anti-TCR mAb is associated with the development of mixed chimerism (MC) and donor-specific tolerance.
Objective of the study:
To analyze the development of MC in face transplant recipients receiving combined VBMT and hematopoietic stem cell (HSC) infusion.
Three face transplantations (TR) were performed in severely disfigured patients (pts) between 2005 and 2012. The facial allograft included nose, lips, cheeks and chin in pt 1, bilateral mandible (VBM), cheeks, lips and chin in pt 2, and bilateral maxilla and mandible (VBM), cheeks, lips, chin and tongue in pt 3. The total donor nucleated HSC infused was 1.6X108 per kg on day 4 and 1.8X 108 per kg on day 11 in pt 1; 1.6X108 per kg on day 4 in pt 2, and 1.83X 108 per kg on day 7 in pt 3. Immunosuppression consisted of Thymoglobulin induction, and triple immunosuppression with tacrolimus, prednisolone and mycophenolate mofetil. Chimerism was assessed by RQ-PCR using whole blood and CD3+ cells weekly for one month and every 3 months after TR, and on total and purified CD34+ bone marrow cells.
Microchimerism was detected once at M2 (0.1% donor cells among the CD34+ cells) in pt 1, in the bone marrow in pt 2 at day 7 (0.4% donor CD34 + cells), day 14 (0.6% donor CD34 + cells), and day 56 (0.4% donor CD34 + cells) and was detected once in peripheral blood (0.6 % donor CD3+ lymphocytes at d28). Chimerism was not evident in pt 3. Two episodes of acute rejection occurred in pt 1, six episodes in pt 2, and one episode in pt 3, suggesting the absence of tolerance induction.
VBMT combined with HSC infusion did not induce MC in face transplant recipients. This study suggests that a non-myeloablative regimen is necessary to induce MC in the context of donor VBMT and HSC infusion.
To cite this abstract in AMA style:Morelon E, Dubois V, Testelin S, Petruzzo P, Badet L, Michallet M, Hequet O, Brunet M, Kanitakis J, Dubernard J, Lengele B, Devauchelle B. Face Transplantation with Combined Hematopoietic Stem Cell Infusion and Vascularized Bone Marrow Transplantation Is Not Associated with Mixed Chimerism in Humans [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/face-transplantation-with-combined-hematopoietic-stem-cell-infusion-and-vascularized-bone-marrow-transplantation-is-not-associated-with-mixed-chimerism-in-humans/. Accessed August 15, 2020.
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