Islet cell transplantation involves the infusion of pancreatic islet cells into the liver by portal vein embolization. Islet cells are prepared from the resected pancreas by injecting a collagenase solution into the pancreas, which frees the cells from acinar tissue. The resultant dispersed pancreatic islet tissue is collected, washed and diluted in plasma. Most often the plasma is then injected slowly into the portal vein of the liver. In some cases, islets are transplanted beneath the kidney capsule.

Medically Necessary:

Autologous pancreatic islet cell transplantation is considered medically necessary as an adjunct to a total or near total pancreatectomy for individuals with chronic pancreatitis.

Investigational and Not Medically Necessary:

Autologous pancreatic islet cell transplantation is considered investigational and not medically necessary for all other applications.

Allogeneic pancreatic islet cell transplantation is considered investigational and not medically necessary in all cases.

Note: For multi-organ transplant requests, criteria must be met for each organ requested. In those situations, an individual may present with a concurrent medical condition which would be considered an exclusion or a comorbidity that would preclude a successful outcome, but would be treated with the other organ transplant. Such cases will be reviewed on an individual basis for coverage determination to assess the member's candidacy for transplantation.

Autologous Pancreatic Islet Cell Transplantation
A total or near total pancreatectomy can relieve pain from chronic pancreatitis, but also results in insulin dependent diabetes. Autologous islet cell transplantation as an adjunct to a total or near total pancreatectomy is a technique which may prevent this outcome from occurring.

In a case series study done by Rodriguez Rilo (2003), 22 patients with severe chronic pancreatitis underwent pancreatectomy and autologous islet cell transplantation at a single institution. Postoperatively, all patients demonstrated C-peptide and insulin production demonstrating graft function. Also, following surgery, 41% were insulin independent and 27% required minimal amounts of insulin on a sliding scale. Four patients experienced major complications which included respiratory distress syndrome (n=2), intra-abdominal abscess (n=1), and pulmonary embolism (n=1). Preoperatively, all patients reported pain and had been taking opioid analgesics. Postoperatively, 82% no longer required analgesics. The investigators concluded that pancreatectomy with autologous islet cell transplantation can alleviate pain for patients with chronic pancreatitis and preserve endocrine function.

Gruessner and colleagues (2004) performed 112 islet autotransplants as an adjunct to total pancreatectomy. Results demonstrated that islet autotransplants performed at the time of total pancreatectomy in patients who had not had previous operations on the body and tail of the pancreas were associated with a high islet yield and >70% of the recipients achieved complete insulin independence. In contrast, patients in this case series with a history of a previous distal pancreatectomy or Puestow drainage procedure (lengthwise attachment of cleared pancreatic duct to the small intestine) had a low islet yield and complete insulin independence was achieved in fewer than 20% of transplanted patients.

Garcea and colleagues (2009) examined 85 patients undergoing total pancreatectomy with and without islet cell transplant. Fifty patients underwent a concomitant autologous islet cell transplant and 35 underwent a pancreatectomy alone. Pain relief, insulin requirements, and glycemic control were evaluated postoperatively. The authors concluded a total pancreatectomy is effective in pain reduction and opioid dependence in chronic pancreatitis patients and the addition of an islet cell transplant resulted in reduction of insulin demands and potential achievement of insulin independence.

Autologous islet cell transplantation appears to significantly decrease the incidence of diabetes after total or near total pancreatectomy for chronic pancreatitis. Additionally, this procedure is not associated with serious complications in itself and is performed as an adjunct to the pancreatectomy procedure. The level of evidence is insufficient to permit conclusions in terms of uses of autologous islet cell transplantation for all other indications.

Allogeneic Pancreatic Islet Cell Transplantation
Pancreatic islet cell transplantation is currently under investigation as a therapy option proposed to restore normoglycemia in labile type 1 diabetes.

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) established the Collaborative Islet Transplant Registry (CITR) in September 2001 and published their first annual report in 2005. This CITR report included data on 86 islet cell transplant recipients. The median age of the deceased donor was 44 years and body mass index was 28.2. At 6 months after the last infusion, 61.1% of the recipients were reported to be insulin independent and at 12 months, 57.9% were reported to be insulin independent. While study results suggest potential promise, the report cautions that "great care must be used in the analysis and in the interpretation and conclusions made from the results," since the data are derived from mostly small, non-randomized pilot trials. The study was also limited by lack of long term health outcomes.

The second analysis of the CITR, published in 2007, reported information on 138 islet transplant recipients. The median age of the deceased donor was 44 years and body mass index was 28.3. At 6 months after the last infusion, 67.0% of the transplant recipients were insulin independent, and at 12 months 58.0% were insulin independent. Over 82% of all recipients experienced one or more severe hypoglycemic events in the year prior to their first infusion. Two recipients (2%) experienced one or more severe hypoglycemic events between 30 days and 12 months post infusion, but both of these recipients were on insulin replacement therapy and one had experienced a complete islet graft failure. Fifteen (13.4%) patients experienced complete graft failure and 3 participants had unknown insulin status at the time of the analysis. Study limitations included a small number of islet cell transplant recipients, centers not reporting on all of their islet cell transplant recipients, lack of randomization, and a potential for bias.

Pancreatic islet cell transplants hold significant potential advantages over whole-gland transplants. However, at this time the evidence is insufficient to conclude that allogeneic islet cell transplantation shows net benefits in type I diabetes or for any other purpose.

Chronic Pancreatitis
Chronic pancreatitis is a progressive disease of the pancreas that results in irreversible deterioration of pancreatic structure and function. Patients with chronic pancreatitis may experience intractable pain that can only be relieved with a total or near total pancreatectomy. However, the pain relief must be balanced against the certainty that the patient will be rendered an insulin-dependent diabetic. Autologous islet cell transplantation has been investigated as a technique to prevent this serious morbidity. Specifically, during the pancreatectomy procedure, a suspension of isolated islet cells is created from the resected pancreas specimen and then injected into the portal vein of the liver, where the cells function as a free graft.

Type 1 Diabetes
Type 1 diabetes is a chronic disease that occurs when the pancreas does not produce enough insulin to properly control blood glucose levels. Transplantation of pancreatic islet cells has been investigated as an alternative to exogenous insulin or pancreas transplantation. Islet cell transplantation is proposed as a treatment for type I diabetes, whether due to unknown causes or to partial or total pancreatectomy for chronic pancreatitis. Three types of islet transplants have been used: allo-transplants isolated from human adult islet tissue (including the use of multiple donors for one recipient in order to obtain a sufficient number of islet cells); transplants isolated from fetal human or animal tissue; and auto-transplants. A variety of tissue sources, methods of islet isolation and preservation, sites of implantation, and immunosuppressive regimens have been investigated.

The American Diabetes Association (2003) notes that pancreatic islet cell transplants hold significant potential advantages over whole-gland transplants. However, at this time, islet cell transplantation for type 1 diabetes is an investigational procedure, also requiring systemic immunosuppression, and should be performed only within the setting of controlled research studies.

There are significant issues requiring further investigation before islet cell transplantation for treatment of diabetes could be considered outside of clinical trials. These issues include:

• Limited islet supply: Based on the number of pancreas donors each year, only a limited number are suitable for transplant. The technique to isolate islets has not been perfected.
• Toxicity of immunosuppression: Patients receive potent immunosuppressive medications for the rest of their lives after a transplant. Therefore, patients also contend with a higher risk for infections resulting from a weakened immune system.
• Normal blood sugar levels not achieved: Only a small percentage of transplant patients achieve normal blood sugar levels.
• Long-term safety: The immediate risks of gaining access to the portal vein of the liver to transplant islet cells include portal vein thrombosis and bleeding. The long-term consequences are not known, but reports of hepatic steatosis have been documented.
• Duration of islet allograft function: In addition to rejection by a patient's immune system, the transplanted islets are susceptible to exhaustion. It is not known how long islets will function after transplantation, and whether the patient will need multiple transplants.
• Effect on diabetic complications: A crucial question is whether islet cell transplantation lowers the risk of diabetes complications, such as coronary artery disease and neuropathy. Currently the long-term results are unknown.

Acinar: any secreting cell lining a gland, especially as applied to the cells of the pancreas that furnish pancreatic juice and enzymes to distinguish them from the islets of Langerhans, which secrete hormones

Allogeneic: derived from individuals related or unrelated to the recipient

Autologous: from the patient's own body

Islet of Langerhans: groups of cells found within the pancreas; A-cells and B-cells which secrete insulin and glucagon

Pancreas: a tongue shaped glandular organ lying below and behind the stomach that secretes insulin and glucagon (both regulate blood sugar), as well as digestive enzymes

The following codes for treatments and procedures applicable to this document are included below for informational purposes.  Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy.  Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services are Medically Necessary: 

When services are Investigational and Not Medically Necessary:
For the procedure codes listed above, for all other diagnoses not listed; or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.

When services may be Medically Necessary:

When services are Investigational and Not Medically Necessary:
For the procedure code listed above when described as autologous transplant for all other diagnoses not listed; or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.

When services are also Investigational and Not Medically Necessary for allogeneic transplantation:

Peer Reviewed Publications:

1. Close N, Alejandro R, Hering B, Appel M; CITR Investigators. Second annual analysis of the collaborative islet transplant registry. Transplant Proc. 2007; 39(1):179-182.
2. Close NC, Hering BJ, Eggerman TL. Results from the inaugural year of the Collaborative Islet Transplant Registry.Transplant Proc. 2005; 37(2):1305-1308.
3. Garcea G, Weaver J, Phillips J, et al. Total pancreatectomy with and without islet cell transplantation for chronic pancreatitis: a series of 85 consecutive patients. Pancreas. 2009; 38 (1):1-7.
4. Gruessner RW, Sutherland DE, Dunn DL, et al. Transplant options for patients undergoing total pancreatectomy for chronic pancreatitis. J Am Coll Surg. 2004; 198(4):559-567.
5. Farney AC, Hering BJ, Nelson L et al. No late failures of intraportal human islet autografts beyond 2 years. Transplantat Proc. 1998; 30(2):420.
6. Markmann JF, Deng S, Huang X, et al. Insulin independence following isolated islet transplantation and single islet infusions. Ann Surg. 2003: 237(6):741-750.
7. Merani S, Shapiro AM, Current status of pancreatic islet transplantation. Clin Sci (Lond). 2006; 110(6):611-625.
8. Pileggi A, Alejandro R, Ricordi C. Clinical islet transplantation.Minerva Endocrinol. 2006 Sep;31(3):219-232.
9. Robertson RP, Davis C, Larsen J, et al. Pancreas and islet transplantation for patients with diabetes. Diabetes Care. 2000; 23(1):112-116. Available at:
   http://care.diabetesjournals.org/cgi/reprint/23/1/112?ijkey=778a864cc7b73ab0c1f0c485fd8bd83bc9696930&keytype2=tf_ipsecsha. Accessed on December31, 2009.
10. Robertson RP. Islet transplantation as a treatment for diabetes – a work in progress. N Engl J Med. 2004; 350(7):694-705.
11. Rodriguez Rilo HL, Ahmad SA, D'Alessio D, et al. Total pancreatectomy and autologous islet cell transplantation as a means to treat severe chronic pancreatitis. J Gastrointest Surg. 2003; 7(8):978-989.
12. Shapiro AM, Lakey JR, Ryan EA, et al. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med. 2000; 343(4):230-238.
13. Wahoff DC, Papalois BE, Najarian JS. Autologous islet transplantation to prevent diabetes after pancreatic resection. Ann Surg 1995; 222(4):562-579.

Government Agency, Medical Society, and Other Authoritative Publications:

1. American Diabetes Association: Position Statement: Pancreas and islet cell transplantation in type 1 diabetes. Diabetes Care. 2006; 29(4); 935.
2. American Diabetes Association: Position Statement: Pancreas transplantation for patients with type 1 diabetes. Diabetes Care. 2003; 26(Suppl 1):S120.
3. Centers for Medicare and Medicaid Services. National Coverage Determination for Islet Cell Transplantation in the Context of a Clinical Trial. NCD #260.3.1. Effective October 1, 2004. Available at: http://www.cms.hhs.gov/mcd/viewncd.asp?ncd_id=260.3.1&ncd_version=1&basket=ncd%3A260%2E3%2E1%3A1%3AIslet+Cell+Transplantation+in+the+Context+of+a+Clinical+Trial. Accessed on December31, 2009.
4. Hayes Inc. Medical Technology Directory. Islet Cell Transplantation for the Treatment of Type 1 Diabetes. Lansdale, PA: Hayes, Inc.; August 2004. Search updated August 24, 2007.
5. Piper M, Seidenfeld J, Aronson N. Islet Transplantation in Patients with Type 1 Diabetes Mellitus. Summary, Evidence Report/Technology Assessment: Number 98. AHRQ Publication Number 04-E017-1, July 2004. Agency for Healthcare Research and Quality, Rockville, MD. Available at: http://www.ahrq.gov/clinic/epcsums/isletsum.htm. Accessed on December 31, 2009.

Allogeneic Islet Cell Transplant
Autologous Islet Cell Transplant
Islet Cell Transplant
Pancreatectomy, Partial or Complete
Pancreatitis