Document Detail


Islet transplantation with alemtuzumab induction and calcineurin-free maintenance immunosuppression results in improved short- and long-term outcomes.
MedLine Citation:
PMID:  19104407     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Tatiana Froud; David A Baidal; Raquel Faradji; Pablo Cure; Davide Mineo; Gennaro Selvaggi; Norma S Kenyon; Camillo Ricordi; Rodolfo Alejandro
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Transplantation     Volume:  86     ISSN:  1534-6080     ISO Abbreviation:  Transplantation     Publication Date:  2008 Dec 
Date Detail:
Created Date:  2008-12-23     Completed Date:  2009-01-27     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  0132144     Medline TA:  Transplantation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1695-701     Citation Subset:  IM    
Affiliation:
Clinical Islet Transplant Program, Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, FL, USA.
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MeSH Terms
Descriptor/Qualifier:
Adult
Antibodies, Monoclonal / therapeutic use*
Antibodies, Monoclonal, Humanized
Antibodies, Neoplasm / therapeutic use*
Antineoplastic Agents / therapeutic use
Blood Glucose / drug effects,  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
Hemoglobin A, Glycosylated / 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
Grant Support
ID/Acronym/Agency:
M01 RR016587-030006/RR/NCRR NIH HHS; M01 RR016587-030009/RR/NCRR NIH HHS; M01 RR016587-030021/RR/NCRR NIH HHS; M01 RR016587-040006/RR/NCRR NIH HHS; M01 RR016587-040009/RR/NCRR NIH HHS; M01 RR016587-040021/RR/NCRR NIH HHS; M01 RR016587-040044/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antibodies, Monoclonal, Humanized; 0/Antibodies, Neoplasm; 0/Antineoplastic Agents; 0/Blood Glucose; 0/C-Peptide; 0/Hemoglobin A, Glycosylated; 0/Hypoglycemic Agents; 0/Immunosuppressive Agents; 0/Insulin; 109581-93-3/Tacrolimus; 3A189DH42V/alemtuzumab; 53123-88-9/Sirolimus; EC 3.1.3.16/Calcineurin
Comments/Corrections

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