Islet cell transplantation involves the infusion of pancreatic islet cells into the liver by portal vein embolization. Islet cells are obtained 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. This document addresses autologous and allogeneic pancreatic islet cell transplantation.

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.

Chronic Pancreatitis 

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 individuals with severe chronic pancreatitis underwent pancreatectomy and autologous islet cell transplantation at a single institution. Postoperatively, all individuals demonstrated C-peptide and insulin production demonstrating graft function, 41% were insulin independent, and 27% required minimal amounts of insulin on a sliding scale. Four persons experienced major complications which included respiratory distress syndrome (n=2), intra-abdominal abscess (n=1), and pulmonary embolism (n=1). Preoperatively, all individuals 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 those with chronic pancreatitis and preserve endocrine function.

Gruessner and colleagues (2004) performed 112 islet autotransplants as an adjunct to total pancreatectomy. Results indicated that islet autotransplants performed at the time of total pancreatectomy in individuals who had not  previously received operations on the body and tail of the pancreas were associated with a high islet yield. Greater than 70% of these recipients achieved complete insulin independence. In contrast, individuals 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. Less than 20% of these recipients achieved complete insulin independence.

Garcea and colleagues (2009) examined 85 individuals undergoing total pancreatectomy with and without islet cell transplant. Fifty individuals 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 those with chronic pancreatitis and the addition of an islet cell transplant resulted in reduction of insulin demands and potential achievement of insulin independence.

Type 1 Diabetes

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

In 2004, the Agency for Healthcare Research and Quality (AHRQ) issued an evidence report on islet transplantation in type 1 diabetes. The evidence report found published data on clinical outcomes of islet alone transplantation are limited by small numbers, few transplant centers, short duration of follow-up, and lack of standardized methods of reporting clinical outcomes. Efforts are ongoing to update and expand long-term transplant results, disseminate protocols to additional centers, and standardize reporting of outcomes.

The 2008 update from the Collaborative Islet Transplant Registry (CITR), which has collected and monitored data on allogeneic islet transplantation in North America, Europe, and Australia since 1999, reported that as of April 2008, their registry comprised of 325 adult recipients and 649 islet infusions from 712 donors. Recipients of allogeneic islet transplants all had type 1 diabetes for more than five years, were between 18 and 65 years of age, and had poor diabetes control. It was noted that at three years post first infusion only 23% of islet-alone recipients were insulin independent (defined as insulin independent two or more weeks), 29% were insulin dependent with detectable C-peptide, 26% had lost function, and 22% had missing data. Seventy percent achieved insulin independence at least once, of whom 71% were still insulin independent one year later and 52% at two years. There have been seven reported deaths among allograft recipients with causes ranging from unknown reasons to viral meningitis possibly related to immunosuppressant therapy, drug toxicity and stroke.

Sutherland and colleagues (2008) studied outcomes for 173 autologous islet recipients after complete pancreatectomy compared with those of allogeneic islet recipients in the CITR. The authors concluded that the islet function is more resilient in autografts than allografts. They noted that the five year insulin-independence persistence rate for autografts is similar to the two year rate for allografts. Several factors unique to allograft cases likely responsible for the differences included longer cold ischemia time, diabetogenic immunosuppression, and auto- and alloimmunity.

The American Diabetes Association (2006), in a position statement on pancreas and islet transplantation in type 1 diabetes, indicates that pancreatic islet transplants require systemic immmunosuppression 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.
• Toxicity of immunosuppression: Transplant recipients receive potent immunosuppressive medications for the rest of their lives after a transplant. Therefore, these individuals also contend with a higher risk for infections resulting from a weakened immune system.
• Normal blood sugar levels not achieved: A low percentage of transplant recipients report normal blood sugar levels at three years post infusion.
• Long-term safety: The long-term consequences are not known.

Conclusion 

Autologous pancreatic 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 currently insufficient to permit conclusions in terms of uses of autologous islet cell transplantation for all other indications.

Allogeneic pancreatic islet cell transplants may potentially hold advantages over whole-gland transplants. However, at this time the level of 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. Individuals 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 individual 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 reported: 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.

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: Derived from the individual'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:

Future ICD-10 coding (effective 10/01/2013)
A draft of ICD-10 Coding related to this document, as it might look today, is available for reference and comments at: Appendix 1: Future ICD-10 coding

Peer Reviewed Publications:

1. Alejandro R, Barton FB, Hering BJ, Wease S; Collaborative Islet Transplant Registry Investigators. 2008 Update from the Collaborative Islet Transplant Registry. Transplantation. 2008; 86(12):1783-1788.
2. 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.
3. Close NC, Hering BJ, Eggerman TL. Results from the inaugural year of the Collaborative Islet Transplant Registry.Transplant Proc. 2005; 37(2):1305-1308.
4. 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.
5. 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.
6. 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.
7. 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.
8. Merani S, Shapiro AM, Current status of pancreatic islet transplantation. Clin Sci (Lond). 2006; 110(6):611-625.
9. Pileggi A, Alejandro R, Ricordi C. Clinical islet transplantation.Minerva Endocrinol. 2006 Sep; 31(3):219-232.
10. 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 December 29, 2010.
11. Robertson RP. Islet transplantation as a treatment for diabetes – a work in progress. N Engl J Med. 2004; 350(7):694-705.
12. 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.
13. 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.
14. Sutherland DE, Gruessner AC, Carlson AM et al. Islet autotransplant outcomes after total pancreatectomy: a contrast to islet allograft outcomes. Transplantation 2008; 86(12):1799-802.
15. 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. 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 29, 2010.

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