Single-Donor, Marginal-Dose Islet Transplantation in Patients With Type 1 Diabetes
2005
ContextIslet allografts from 2 to 4 donors can reverse type 1 diabetes. However,
for islet transplants to become a widespread clinical reality, diabetes reversal
must be achieved with a single donor to reduce risks and costs and increase
the availability of transplantation.ObjectiveTo assess the safety of a single-donor, marginal-dose islet transplant
protocol using potent induction immunotherapy and less diabetogenic maintenance
immunosuppression in recipients with type 1 diabetes. A secondary objective
was to assess the proportion of islet transplant recipients who achieve insulin
independence in the first year after single-donor islet transplantation.Design, Setting, and ParticipantsProspective, 1-year follow-up trial conducted July 2001 to August 2003
at a single US center and enrolling 8 women with type 1 diabetes accompanied
by recurrent hypoglycemia unawareness or advanced secondary complications.InterventionsStudy participants underwent a primary islet allotransplant with 7271
(SD, 1035) islet equivalents/kg prepared from a single cadaver donor pancreas.
Induction immunosuppression was with antithymocyte globulin, daclizumab, and
etanercept. Maintenance immunosuppression consisted of mycophenolate mofetil,
sirolimus, and no or low-dose tacrolimus.Main Outcome MeasuresSafety (assessed by monitoring the severity and duration of adverse
events) and efficacy (assessed by studying the recipients’ insulin requirements,
C-peptide levels, oral and intravenous glucose tolerance results, intravenous
arginine stimulation responses, glycosylated hemoglobin levels, and hypoglycemic
episodes) associated with the study transplant protocol.ResultsThere were no serious, unexpected, or procedure- or immunosuppression-related
adverse events. All 8 recipients achieved insulin independence and freedom
from hypoglycemia. Five remained insulin-independent for longer than 1 year.
Graft failure in 3 recipients was preceded by subtherapeutic sirolimus exposure
in the absence of measurable tacrolimus trough levels.ConclusionsThe tested transplant protocol restored insulin independence and protected
against hypoglycemia after single-donor, marginal-dose islet transplantation
in 8 of 8 recipients. These results may be related to improved islet engraftment
secondary to peritransplant administration of antithymocyte globulin and etanercept.
These findings may have implications for the ongoing transition of islet transplantation
from clinical investigation to routine clinical care.
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