title: Age and Early Graft Function Relate With Risk-Benefit Ratio of Allogenic Islet Transplantation Under Antithymocyte Globulin-Mycophenolate Mofetil-Tacrolimus Immune Suppression.
abstract: Induction therapy with a T cell-depleting agent followed by mycophenolate mofetil and tacrolimus is presently the most frequently used immune suppression (IS) regimen in islet transplantation. This study assesses its safety and tolerability in nonuremic type 1 diabetic recipients.
  
  
  
  Fifty-one patients (age, between 29 and 63 years) with high glycemic variability and problematic hypoglycemia received intraportal islet grafts under anti-thymocyte globulin-mycophenolate mofetil-tacrolimus protocol. They were followed up for over 48 months for function of the implant and adverse events.
  
  
  
  Severe hypoglycemia and diabetic ketoacidosis were absent in patients with functioning graft. Immune suppressive therapy was maintained for 48 months in 29 recipients with sustained function (group A), whereas 16 patients stopped earlier due to graft failure (group B) and in 6 for other reasons. Group A was significantly older at the time of implantation and achieved higher graft function at posttransplantation month 6 under similar dose of IS. Prevalence of IS-related side effects was similar in groups A and B, occurring predominantly during the first year posttransplantation. IS-related serious adverse events (SAE) were reported in 47% of patients, with 4 presenting with cytomegalovirus infection and 4 (age, 42-59 years) diagnosed with cancer. Except in 1 patient with cancer, all SAEs resolved after appropriate treatment.
  
  
  
  These risk/benefit data serve as a basis for clinical decision-making before entering an intraportal islet transplantation protocol. A longer benefit is observed in recipients of higher age (≥40 years), but it is not associated with more side effects and SAE.
authors: 1 Department of Clinical and Experimental Medicine, Katholieke Universiteit Leuven and University Hospitals Leuven, Leuven, Belgium. 2 University Hospital and Diabetes Research Center, Vrije Universiteit Brussel (VUB), Brussels, Belgium. 3 Department of Interventional Radiology, University Hospitals Leuven, KUL, Leuven, Belgium. 4 Department of Endocrinology, Gent University Hospital, Gent, Belgium. 5 Department of Endocrinology, Université Libre de Bruxelles-Hôpital Erasme, Bruxelles, Belgium. 6 Department of Diabetology, University Hospital Antwerp-UA, Antwerp, Belgium.
authors: DaHae
authors: D
authors: Lee
authors: Bart
authors: B
authors: Keymeulen
authors: Robert
authors: R
authors: Hilbrands
authors: Zhidong
authors: Z
authors: Ling
authors: Ursule
authors: U
authors: Van de Velde
authors: Daniel
authors: D
authors: Jacobs-Tulleneers-Thevissen
authors: Geert
authors: G
authors: Maleux
authors: Bruno
authors: B
authors: Lapauw
authors: Laurent
authors: L
authors: Crenier
authors: Christophe
authors: C
authors: De Block
authors: Chantal
authors: C
authors: Mathieu
authors: Daniel
authors: D
authors: Pipeleers
authors: Pieter
authors: P
authors: Gillard
mesh_terms: D000328:Adult; D000961:Antilymphocyte Serum / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000601:surgery*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016381:Islets of Langerhans Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000627:therapeutic use*; D011183:Postoperative Complications / Q000209:etiology; D018570:Risk Assessment; D012307:Risk Factors; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D000961:Antilymphocyte Serum; D015415:Biomarkers; D001786:Blood Glucose; D002096:C-Peptide; D007166:Immunosuppressive Agents; C512542:thymoglobulin; D009173:Mycophenolic Acid; D016559:Tacrolimus