TY - JOUR
T1 - Combined islet and hematopoietic stem cell allotransplantation
T2 - A clinical pilot trial to induce chimerism and graft tolerance
AU - Mineo, D.
AU - Ricordi, C.
AU - Xu, X.
AU - Pileggi, A.
AU - Garcia-Morales, R.
AU - Khan, A.
AU - Baidal, D. A.
AU - Han, D.
AU - Monroy, K.
AU - Miller, J.
AU - Pugliese, A.
AU - Froud, T.
AU - Inverardi, L.
AU - Kenyon, N. S.
AU - Alejandro, R.
PY - 2008/6
Y1 - 2008/6
N2 - To prevent graft rejection and avoid immunosuppression-related side-effects, we attempted to induce recipient chimerism and graft tolerance in islet transplantation by donor CD34+hematopoietic stem cell (HSC) infusion. Six patients with brittle type 1 Diabetes Mellitus received a single-donor allogeneic islet transplant (8611 ± 2113 IEQ/kg) followed by high doses of donor HSC (4.3 ± 1.9 × 106 HSC/kg), at days 5 and 11 posttransplant, without ablative conditioning. An 'Edmonton-like' immunosuppression was administered, with a single dose of anti-TNFα antibody (Infliximab) added to induction. Immunosuppression was weaned per protocol starting 12 months posttransplant. After transplantation, glucose control significantly improved, with 3 recipients achieving insulin-independence for a short time (24 ± 23 days). No severe hypoglycemia or protocol-related adverse events occurred. Graft function was maximal at 3 months then declined. Two recipients rejected within 6 months due to low immunosuppressive trough levels, whereas 4 completed 1-year follow-up with functioning grafts. Graft failure occurred within 4 months from weaning (478 ± 25 days posttransplant). Peripheral chimerism, as donor leukocytes, was maximal at 1-month (5.92 ± 0.48%), highly reduced at 1-year (0.20 ± 0.08%), and was undetectable at graft failure. CD25+T-lymphocytes significantly decreased at 3 months, but partially recovered thereafter. Combined islet and HSC allotransplantation using an 'Edmonton-like' immunosuppression, without ablative conditioning, did not lead to stable chimerism and graft tolerance.
AB - To prevent graft rejection and avoid immunosuppression-related side-effects, we attempted to induce recipient chimerism and graft tolerance in islet transplantation by donor CD34+hematopoietic stem cell (HSC) infusion. Six patients with brittle type 1 Diabetes Mellitus received a single-donor allogeneic islet transplant (8611 ± 2113 IEQ/kg) followed by high doses of donor HSC (4.3 ± 1.9 × 106 HSC/kg), at days 5 and 11 posttransplant, without ablative conditioning. An 'Edmonton-like' immunosuppression was administered, with a single dose of anti-TNFα antibody (Infliximab) added to induction. Immunosuppression was weaned per protocol starting 12 months posttransplant. After transplantation, glucose control significantly improved, with 3 recipients achieving insulin-independence for a short time (24 ± 23 days). No severe hypoglycemia or protocol-related adverse events occurred. Graft function was maximal at 3 months then declined. Two recipients rejected within 6 months due to low immunosuppressive trough levels, whereas 4 completed 1-year follow-up with functioning grafts. Graft failure occurred within 4 months from weaning (478 ± 25 days posttransplant). Peripheral chimerism, as donor leukocytes, was maximal at 1-month (5.92 ± 0.48%), highly reduced at 1-year (0.20 ± 0.08%), and was undetectable at graft failure. CD25+T-lymphocytes significantly decreased at 3 months, but partially recovered thereafter. Combined islet and HSC allotransplantation using an 'Edmonton-like' immunosuppression, without ablative conditioning, did not lead to stable chimerism and graft tolerance.
KW - Chimerism
KW - Graft tolerance
KW - Hematopoietic stem cells
KW - Islet transplantation
KW - Type 1 diabetes
UR - http://www.scopus.com/inward/record.url?scp=44449155884&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=44449155884&partnerID=8YFLogxK
U2 - 10.1111/j.1600-6143.2008.02230.x
DO - 10.1111/j.1600-6143.2008.02230.x
M3 - Article
C2 - 18444924
AN - SCOPUS:44449155884
SN - 1600-6135
VL - 8
SP - 1262
EP - 1274
JO - American Journal of Transplantation
JF - American Journal of Transplantation
IS - 6
ER -