Combined islet and hematopoietic stem cell allotransplantation: A clinical pilot trial to induce chimerism and graft tolerance

D. Mineo, C. Ricordi, X. Xu, A. Pileggi, R. Garcia-Morales, A. Khan, D. A. Baidal, D. Han, K. Monroy, J. Miller, A. Pugliese, T. Froud, L. Inverardi, N. S. Kenyon, R. Alejandro

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1262-1274
Number of pages13
JournalAmerican Journal of Transplantation
Volume8
Issue number6
DOIs
StatePublished - Jun 2008

Keywords

  • Chimerism
  • Graft tolerance
  • Hematopoietic stem cells
  • Islet transplantation
  • Type 1 diabetes

ASJC Scopus subject areas

  • Immunology

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