Edmonton Protocol Shows Safety,
Efficacy of Islet-Alone Transplantation
Islet-alone transplantation is safe and effective,
and the Edmonton Protocol used to accomplish this
can be safely replicated.
Preliminary findings were presented last Sunday
during the first plenary session of the American
Transplant Congress, the joint meeting of the
American Society of Transplantation and the American
Society of Transplant Surgeons.
On behalf of the Immune Tolerance Network, James
Shapiro, MD, from the University of Alberta in
Edmonton, Canada, presented the results of islet-alone
transplantation in the first 36 patients enrolled
at nine international sites. A total of 49 transplants
have been performed. The first transplants took
place in November 2001. The immunosuppression
regimen included daclizumab, sirolimus, and tacrolimus.
Median follow-up is 9.4 months.
To be eligible for the study, patients had to
have type 1 diabetes with stable insulin requirements,
a weight limit of 70 kg or less, an adequate renal
reserve defined as a creatinine clearance of greater
than 80 mL/min, and no progressive diabetic complications.
There are 14 men and 22 women in the study. Average
age is 48 years, and average duration of diabetes
is 26 years.
The primary endpoint of the trial is insulin independence.
Secondary endpoints include metabolic parameters,
such as stable hemoglobin A1c, glucose tolerance,
and stimulation tests.
To date, 52% of the patients who have received
any transplants are insulin-independent, while
82.3% of those in whom transplants have been completed
are insulin-independent; some patients have required
up to three transplants.
As a whole, glucose control was abnormal in 92%
of patients prior to islet transplantation. Glucose
control is normal in 75% afterward.
There have been no deaths in the study. There
have been two cases of severe neutropenia, which
are the only two life-threatening events to date,
and 15 cases of severe adverse events, including
bleeding at the percutaneous portal access site,
transient elevation in liver function tests, mouth
ulcerations, neutropenia, leukopenia, thrombocytopenia,
and hypercholesterolemia. All patients were C-peptide
negative prior to surgery and 94% are C-peptide
positive now.
Nineteen percent of patients were receiving statin
therapy for hyperlipidemia prior to transplantation,
and 39% began taking statins afterward. The remaining
42% remain statin-free.
"There was a considerable variation in success
of islet transplantation between the different
sites," Dr. Shapiro reported. It ranged from
a high of 90% at the Edmonton site to 23% success
rate in some of the other sites. "This reflects
a learning curve here," he noted. "[The
findings] emphasize a need for dynamic training
and...longer follow-up to define safety, quality
of life issues, and the impact of possible secondary
complications."
Rodolfo Alejandro, MD, from the University of
Miami in Florida, reported the results of the
15 patients to undergo islet transplantation at
that institution. Thirteen are insulin-independent
at this point under a steroid-free immunosuppressive
regimen, he said. He added that there appears
to be partial islet loss or a loss of islet mass
over time, a finding that needs further exploration.
Thierry Berney, MD, from Geneva University Hospital
in Switzerland, reported results of islet transplantation
in five patients at his center. He said that three,
or 60%, are insulin-free at this point, and "I
am confident that we can raise that number to
80% with a third transplantation in one patient,"
he told Medscape. Two patients have undergone
two transplants to date.
""Personally, what I'm most concerned
about is the complication rate," Dr. Berney
said. "There is about a 10% procedural complication
rate, which is what you would expect. But almost
all of the patients have at least one side effect
of rapamycin. And almost all have dyslipidemia
and are on statin therapy."
"Islet transplantation holds potential as
augmentation in the treatment of diabetes, possibly
as an alternative option to pancreas transplantation,"
Dr. Turka said. Even further down the road, he
speculated that islet transplantation could even
replace pancreas transplantation. "That's
certainly nowhere near the case now," he
hastened to add.
The primary endpoint of this trial has been achieved,
the investigators reported at the American Transplant
Congress. "Clearly the Edmonton Protocol
has been successfully replicated," Dr. Shapiro
announced.
ATC 2003 Annual Meeting: Abstract 3, presented
June 1, 2003; abstract 401, presented June 2,
2003.
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Did YOU KNOW:
Those over18 years with blood pressure ranging
from 120/80 to 139/89 mm Hg belong to the new
category "prehypertension," a high-risk
precursor to hypertension. That, according to
the Joint National Committee 7 report.
