Islet transplantation with alemtuzumab induction and calcineurin-free maintenance immunosuppression results in improved short- and long-term outcomes

Transplantation. 2008 Dec 27;86(12):1695-701. doi: 10.1097/TP.0b013e31819025e5.

Abstract

Background: Only a minority of islet transplant recipients maintain insulin independence at 5 years under the Edmonton protocol of immunosuppression. New immunosuppressive strategies are required to improve long-term outcomes.

Materials and methods: Three subjects with unstable type 1 diabetes mellitus underwent islet transplantation with alemtuzumab induction and sirolimus-tacrolimus maintenance for 3 months and then sirolimus-mycophenolic acid maintenance thereafter. Follow-up was more than 2 years. Comparison was with 16 historical subjects transplanted under the Miami version of the Edmonton protocol.

Results: Insulin independence was achieved in 2 of 3 alemtuzumab and 14 of 16 historical subjects. Those who did not achieve insulin independence only received a single islet infusion. Insulin-independence rates remained unchanged in the alemtuzumab group, but decreased from 14 of 16 (88%) to 6 of 16 (38%) in the historical group over 2 years. Insulin requirements increased in the historical group while remaining stable in the alemtuzumab group. Comparison of functional measures at 3 months suggested better engraftment with alemtuzumab (P=NS). Further comparison of alemtuzumab versus historical groups, up to 24 months, demonstrated significantly better: Mixed meal stimulation index (24 months, 1.0+/-0.08 [n=3] vs. 0.5+/-0.06 pmol/mL [n=6], P<0.01), mixed meal peak C-peptide (24 months, 5.0+/-0.5 [n=3] vs. 3.1+/-0.3 nmol/mL [n=6], P<0.05), HbA1c (24 months, 5.4+/-0.15 [n=3] vs. 6.3+/-0.12 pmol/mL [n=10], P<0.01). Administration of alemtuzumab was well tolerated. There was no increased incidence of infections in alemtuzumab subjects despite profound, prolonged lymphocyte depletion.

Conclusions: Islet transplantation with alemtuzumab induction was well tolerated and resulted in improved short- and long-term outcomes. Further investigation is underway for validation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alemtuzumab
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Neoplasm / therapeutic use*
  • Antineoplastic Agents / therapeutic use
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Body Mass Index
  • C-Peptide / blood
  • Calcineurin
  • Diabetes Mellitus, Type 1 / surgery*
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Follow-Up Studies
  • Glucose Tolerance Test
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Immunosuppressive Agents / therapeutic use
  • Insulin / therapeutic use
  • Islets of Langerhans Transplantation / immunology*
  • Sirolimus / therapeutic use
  • Tacrolimus / therapeutic use
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Neoplasm
  • Antineoplastic Agents
  • Blood Glucose
  • C-Peptide
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Immunosuppressive Agents
  • Insulin
  • Alemtuzumab
  • Calcineurin
  • Sirolimus
  • Tacrolimus