Autologous pancreas islet cell transplantation meets primary coverage criteria for effectiveness and is covered as an adjunct to a total or near total pancreatectomy in patients with chronic pancreatitis.

Autologous islet cell transplantation has been investigated since 1977. Since then the experience has grown slowly with incremental improvements in the islet cell isolation process. Researchers at the University of Minnesota have reported the largest experience, summarizing the results in 48 patients undergoing the procedure between 1977 and 1995.  Of the 39 evaluable patients, 51% were insulin independent for at least 1 month, with the probability of sustained insulin independence dropping to 34% after 2 years. However, of the 18 patients who received an autotransplant with islets prepared with the most recent techniques in islet cell isolation, the long term success rate was 55%. The most powerful predictor of insulin independence was the number of islet cells infused, which in turn is inversely related to the degree of fibrosis of the pancreas. In a small longitudinal study of 6 patients, Robertson and colleagues reported 5 patients remained free of insulin treatment for up to 13 (6.2 +/- 1.7) years after intrahepatic islet autotransplantation.  This study also reported a correlation between the number of islets transplanted to insulin response. Unfortunately, there is currently no way to predict preoperatively the number of islets cells isolated, although patients with long-standing pancreatitis and prior surgical procedures are more likely to have a fibrotic pancreas. There have been no reports of significant morbidity or mortality associated with this procedure. Although the published experience with this procedure is limited, autologous islet cell transplantation appears to significantly decrease the incidence of diabetes after total or near total pancreatectomy. In addition, this procedure is not associated with serious complications itself and is performed as an adjunct to the pancreatectomy procedure.

 

A literature review for the period of June 2005 through September 2006 did not identify any clinical trials that would alter the conclusions reached here. Therefore, the policy statements are unchanged. Froud and colleagues randomized 16 type 1 diabetes mellitus patients to evaluate cultured islet transplantation with or without tumor necrosis factor (TNF-alpha) blockade using Infliximab just prior to islet infusion.  Insulin independence was achieved in 14 patients after 1–2 infusions and was maintained in 11 patients after 1 year and in 6 patients at 18 and 336 months without additional infusions. The authors reported no identifiable clinical benefit with the use of Infliximab but concluded cultured human islet allografts produced results comparable to freshly transplanted islets including normalization of HbA1c. Shapiro reported on 36 patients with type 1 diabetes mellitus who had islet transplantation.  While short-term results were promising, insulin independence was generally not sustainable; 5 patients were insulin-independent at 2 years.

 

A search of the MEDLINE database was performed for the period of October 2006 through January 2008. Several review articles indicate that islet cell transplantation is a promising alternative to pancreas transplantation, but a number of issues need to be resolved for this procedure to be as successful as solid organ transplantation.  

 

The second analysis of the Collaborative Islet Transplant Registry (CITR) reported data on 138 islet transplants from 19 (out of 27) active North American transplant centers.  Fifteen (13%) of 112 islet-only transplants failed. Insulin independence was obtained in 67% of patients at 6 months, decreasing to 58% at 1 year. The 39 (35%) islet-transplant recipients who were insulin dependent at 1 year had an average 69% reduction (range of 17% to 93%) in daily insulin requirements. Registry data indicated that while 82% of patients had experienced at least one severe hypoglycemic episode in the year before transplant, only 2 (2%) patients experienced a severe hypoglycemic episode in the 6-12 month period after infusion. These preliminary (registry-based) results suggest that partial transplant survival might reduce the need for exogenous insulin and the occurrence of severe hypoglycemic events.

 

A multicenter phase I/II trial (10 patients) from GRAGIL 2 (Groupe de Recherche Rhin Rhone Alpes Geneve poor la transplantation d’Ilots de Langerhans) also reported on partial improvements following islet transplantation. Organs were processed at a single site and (accompanied by a physician from the islet isolation team who supervised the procedure) transported to one of the transplantation centers. Based on previously defined metabolic criteria, 3 (30%) patients were considered insulin independent at 1 year. According to a secondary measure of successful islet transplantation (a combination of c-peptide and HbA1c levels, disappearance of hypoglycemic events and a 30% or greater reduction in exogenous insulin needs), 50% of patients were considered to have had successful transplants. Longer-term prospective studies are needed to assess maintenance of hypoglycemic control and disease progression. This procedure is considered investigational; the policy statements are unchanged.