G-CSF and Exenatide Might Be Associated with Increased Long-Term Survival of Allogeneic Pancreatic Islet Grafts.
BACKGROUND
Allogeneic human islet transplantation is an effective therapy for the treatment of patients with Type 1 Diabetes (T1D). The low number of islet transplants performed worldwide and the different transplantation protocols used limit the identification of the most effective therapeutic options to improve the efficacy of this approach.


METHODS
We present a retrospective analysis on the data collected from 44 patients with T1D who underwent islet transplantation at our institute between 2000 and 2007. Several variables were included: recipient demographics and immunological characteristics, donor and transplant characteristics, induction protocols, and additional medical treatment received. Immunosuppression was induced with anti-CD25 (Daclizumab), alone or in association with anti-tumor necrosis factor alpha (TNF-α) treatments (Etanercept or Infliximab), or with anti-CD52 (Alemtuzumab) in association with anti-TNF-α treatments (Etanercept or Infliximab). Subsets of patients were treated with Filgrastim for moderate/severe neutropenia and/or Exenatide for post prandial hyperglycemia.


RESULTS
The analysis performed indicates a negative association between graft survival (c-peptide level ≥ 0.3 ng/ml) and islet infusion volume, with the caveat that, the progressive reduction of infusion volumes over the years has been paralleled by improved immunosuppressive protocols. A positive association is instead suggested between graft survival and administration of Exenatide and Filgrastim, alone or in combination.


CONCLUSIONS
This retrospective analysis may be of assistance to further improve long-term outcomes of protocols for transplant of islets and other organs.
Diabetes Research Institute, University of Miami, Miami, Florida, United States of America.
Alessia
A
Zoso
Microbiology Immunology Department, University of Miami, Miami, Florida, United States of America.
Paolo
P
Serafini
Diabetes Research Institute, University of Miami, Miami, Florida, United States of America.
Giacomo
G
Lanzoni
Diabetes Research Institute, University of Miami, Miami, Florida, United States of America.
Eduardo
E
Peixoto
Department of Public Health Sciences, University of Miami, Miami, Florida, United States of America.
Shari
S
Messinger
Department of Public Health Sciences, University of Miami, Miami, Florida, United States of America.
Alejandro
A
Mantero
Diabetes Research Institute, University of Miami, Miami, Florida, United States of America.
Nathalia D
ND
Padilla-Téllez
Diabetes Research Institute, University of Miami, Miami, Florida, United States of America.
David A
DA
Baidal
Diabetes Research Institute, University of Miami, Miami, Florida, United States of America.
Rodolfo
R
Alejandro
Diabetes Research Institute, University of Miami, Miami, Florida, United States of America.
Camillo
C
Ricordi
Diabetes Research Institute, University of Miami, Miami, Florida, United States of America.
Luca
L
Inverardi
D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000077561:Daclizumab; D000077270:Exenatide; D000069585:Filgrastim / Q000627:therapeutic use*; D006085:Graft Survival / Q000187:drug effects*; D006401:Hematologic Agents / Q000627:therapeutic use*; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy / Q000209:etiology; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007074:Immunoglobulin G / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007515:Islets of Langerhans / Q000187:drug effects* / Q000502:physiology; D016381:Islets of Langerhans Transplantation / Q000009:adverse effects / Q000379:methods*; D008875:Middle Aged; D009503:Neutropenia / Q000188:drug therapy / Q000209:etiology; D010455:Peptides / Q000627:therapeutic use*; D012189:Retrospective Studies; D014184:Transplantation, Homologous; D014688:Venoms / Q000627:therapeutic use*
D061067:Antibodies, Monoclonal, Humanized; D006401:Hematologic Agents; D007004:Hypoglycemic Agents; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D010455:Peptides; D014688:Venoms; D000077270:Exenatide; D000077561:Daclizumab; D000069585:Filgrastim