Age and early graft function relate with risk-benefit ratio of allogenic islet transplantation under Anti-thymocyte globulin - Mycophenolate mofetil - Tacrolimus immune suppression

BACKGROUND: Induction therapy with a T cell depleting agent followed by mycophenolate mofetil (MMF) and tacrolimus (Tac) 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.

METHODS: Fifty-one patients (ages between 29-63 years) with high glycemic variability and problematic hypoglycemia received intraportal islet grafts under anti-thymocyte globulin (ATG)-MMF-Tac protocol. They were followed over 48 months for function of the implant and adverse events.

RESULTS: 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) while in 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 posttransplant (PT) month 6 under similar dose of IS. Prevalence of IS-related side effects was similar in group A and B, occurring predominantly during the first year PT. IS-related serious adverse events (SAE) were reported in 47% of patients, with 4 presenting with CMV infection and 4 (age 42 to 59 years) diagnosed with cancer. Except in 1 patient with cancer, all SAE resolved after appropriate treatment.

CONCLUSIONS: 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 yrs), but it is not associated with more side effects and SAE.