Factors associated with successful islet cell transplantation

This prospective, observational analysis sought to determine the factors associated with favourable outcomes of islet cell transplantation. A total of 398 people with type 1 diabetes who were C-peptide-negative and underwent islet transplantation were followed up >1 year and up to 10 years after transplantation. People who underwent islet-after-kidney or simultaneous-islet/kidney transplantation were excluded; this analysis was limited to those who underwent islet cell transplantation alone (for whom the benefits of islet cell transplantation need to be weight against the risks associated with immunosuppression).

Six outcomes (including various HbA_1c, fasting glucose and C-peptide levels, absence of severe hypoglycaemia and exogenous insulin independence) were used to define successful transplantation. Analysis revealed that, perhaps surprisingly, only four clinical factors were strong predictors of all six favourable outcomes. These were:

• Recipient age ≥35 years.
• A total of ≥325 000 islet cell equivalents infused over one or more infusions.
• Administration of T-cell-depleting antibodies and/or TNF-α inhibition from first transplant.
• Maintenance with calcineurin inhibitors (CNI) and mTOR inhibitors for at least some portion of follow-up.

At 5 years after the last islet infusion, of the recipients who met these four common factors (N=126), 95% were free of severe hypoglycaemia, 76% had an HbA_1c <53 mmol/mol and 53% were insulin-independent, significantly higher rates than were seen in participants who did meet all four factors (N=272). The rate of serious adverse events due to the procedure or immunosuppression was low (around 0.06 events per person) in both groups.

The authors point out that these four factors are few and, with the exception of age, controllable and achievable with current practices. Furthermore, even in younger people, the positive outcome rates were only around 5% lower if all three other factors were met. Therefore, age alone should not be considered a disqualifying factor for islet cell transplantation.

The authors conclude that these findings provide important new insights to guide transplant centres in developing and refining islet cell transplant protocols.

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