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.
| Original language | English |
|---|---|
| Pages (from-to) | 1695-1701 |
| Number of pages | 7 |
| Journal | Transplantation |
| Volume | 86 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 27 2008 |
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Keywords
- Alemtuzumab
- Calcineurin free
- Graft survival and function
- Islet transplantation
ASJC Scopus subject areas
- Transplantation
Cite this
Islet transplantation with alemtuzumab induction and calcineurin-free maintenance immunosuppression results in improved short- and long-term outcomes. / Froud, Tatiana; Baidal, David; Faradji, Raquel; Cure, Pablo; Mineo, Davide; Selvaggi, Gennaro; Kenyon, Norma S; Ricordi, Camillo; Alejandro, Rodolfo.
In: Transplantation, Vol. 86, No. 12, 27.12.2008, p. 1695-1701.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Islet transplantation with alemtuzumab induction and calcineurin-free maintenance immunosuppression results in improved short- and long-term outcomes
AU - Froud, Tatiana
AU - Baidal, David
AU - Faradji, Raquel
AU - Cure, Pablo
AU - Mineo, Davide
AU - Selvaggi, Gennaro
AU - Kenyon, Norma S
AU - Ricordi, Camillo
AU - Alejandro, Rodolfo
PY - 2008/12/27
Y1 - 2008/12/27
N2 - 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.
AB - 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.
KW - Alemtuzumab
KW - Calcineurin free
KW - Graft survival and function
KW - Islet transplantation
UR - http://www.scopus.com/inward/record.url?scp=58849101815&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=58849101815&partnerID=8YFLogxK
U2 - 10.1097/TP.0b013e31819025e5
DO - 10.1097/TP.0b013e31819025e5
M3 - Article
C2 - 19104407
AN - SCOPUS:58849101815
VL - 86
SP - 1695
EP - 1701
JO - Transplantation
JF - Transplantation
SN - 0041-1337
IS - 12
ER -