Coverage Policy Manual
Policy #: 2003014
Category: Surgery
Initiated: June 2003
Last Review: July 2018
  Transplant, Autologous Islet Cell for Chronic Pancreatitis

Description:
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.
 
Coding
CPT code 48160 explicitly describes autologous pancreas islet cell transplantation at the time of pancreatectomy. CPT instructs the use of code 48999 (unlisted procedure, pancreas) for transplantation of islet cells as a standalone procedure.
 
Effective October 1, 2004, there are 3 HCPCS codes specific to these procedures:
 
G0341 Percutaneous islet cell transplant, includes portal vein catheterization and infusion
G0342 Laparoscopy for islet cell transplant, includes portal vein catheterization and infusion
G0343 Laparotomy for islet cell transplant, includes portal vein catheterization and infusion
 

Policy/
Coverage:
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.

Rationale:
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.
 
2006 Update
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.
 
2007-2008 Update
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.
 
2012 Update
A search of the MEDLINE database was conducted through June 2012. There was no new literature identified that would prompt a change in the coverage statement.
 
2013 Update
A literature search conducted through June 2013 did not reveal any new information that would prompt a change in the coverage statement.
 
2014 Update
 
A literature search conducted through June 2014 did not reveal any new information that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
A 2014 study by Chinnakotla et al included 484 patients with chronic pancreatitis (Chinnakotla, 2014). Patients underwent total pancreatectomy and immediate islet auto transplantation. Using a Kaplan-Meier analysis method, 10-year survival was 84%. Patient survival at 5 years was 90.3% in the 80 patients with hereditary/genetic pancreatitis and 89.7% in the 404 patients with nonhereditary pancreatitis; the difference between groups was not statistically significant. Pancreatitis pain decreased significantly after the procedures, and there was no statistically significant difference in the rate of pancreatitis pain between the groups with and without genetic/hereditary disease.
 
2015 Update
A literature search conducted through May 2015 did not reveal any new information that would prompt a change in the coverage statement.  The key identified literature is summarized below.
 
Chronic Pancreatitis
There are several systematic reviews of the literature on chronic pancreatitis patients. In 2015, Wu and colleagues published a systematic review of studies on islet transplantation after total pancreatectomy for chronic pancreatitis (Wu, 2015). Studies could use any type of design but needed to include at least 5 patients or have a median follow-up of at least 6 months. Twelve studies with a total of 677 patients met the review’s inclusion criteria. The mean age of the patients was 38 years and mean duration of pancreatitis was 6.6 years. A meta-analysis of the insulin independence rate at 1 year (5 studies, 362 patients) was 28.4% (95% confidence interval [CI]: 15.7 to 46.0%). At 2 years, the pooled insulin independence rate (3 studies, 297 patients) was 19.7% (95% CI: 5.1 to 52.6%). The pooled 30 day mortality rate (11 studies) was 2.1% (95% CI: 1.2 to 3.8%). Long-term mortality data were not pooled.
 
In 2014, Wilson and colleagues reported on 166 patients age 14 or older with chronic pancreatitis who underwent total pancreatectomy and islet transplantation at a single center (Wilson. 2014).  Actuarial survival at 5 years was 94.6%. Five year or longer data were available for 112 patients (67%). At 1 year 38% of patients were insulin dependent and the declined to 27% at the 5-year follow-up. Daily insulin requirement, however, remained stable over the 5 years. Fifty-five percent of patients were narcotic independent at 1 year, and this increased to 73% at 5 years.
 
Type 1 Diabetes
According to FDA industry guidance on evaluating allogeneic pancreatic islet cell products, published in 2009, single arm trials with historical controls may be acceptable alternatives to RCTs for evaluating the safety and efficacy of islet cell products in patients with metabolically unstable type 1 diabetes (FDA, 2009). Attainment of normal range HbA1c level (ie ≤6.5%) and elimination of hypoglycemia are acceptable primary endpoints. To assess durability of the islet cell procedure, primary endpoints should be measured at least 12 months after the final infusion. Other key clinical outcomes include insulin independence, measures of glucose metabolic control such as fasting plasma glucose level and loss of hypoglycemia unawareness.
 
2018 Update
A literature search was conducted through June 2018.  There was no new information identified that would prompt a change in the coverage statement.  The key identified literature is summarized below.
 
TYPE 1 DIABETES
 
A systematic review by Health Quality Ontario reported on islet transplantation for patients with
type 1 diabetes (HQO, 2015). Most of the evidence was from case series derived at single centers. For nonuremic patients, rates of insulin independence ranged from 30% to 70% from observational case series at 1 year after islet transplantation. For uremic patients, reported insulin-independence rates ranged from 20% to 67%. Evidence of changes in secondary complications such as diabetic retinopathy and nephropathy were conflicting across different studies.

CPT/HCPCS:
48160Pancreatectomy, total or subtotal, with autologous transplantation of pancreas or pancreatic islet cells
G0341Percutaneous islet cell transplant, includes portal vein catheterization and infusion
G0342Laparoscopy for islet cell transplant, includes portal vein catheterization and infusion
G0343Laparotomy for islet cell transplant, includes portal vein catheterization and infusion

References: Centers for Medicare and Medicaid.(2017) National Coverage Determination (NCD) for ISLET CELL Transplantation in the Context of a Clinical Trial (260.3.1). 2004; https://www.cms.gov/medicare-coverage-database/details/ncddetails.aspx?NCDId=286&ncdver=1&CoverageSelection=Both&ArticleType=All&PolicyType=Final&s=All&KeyWord=islet+cell&KeyWordLookUp=Title&KeyWordSearchType=And&bc=gAAAABAAAAAA&. Accessed August 4, 2017.

Chinnakotla S, Radosevich DM, Dunn TB et al.(2014) Long-term outcomes of total pancreatectomy and islet auto transplantation for hereditary/genetic pancreatitis. J Am Coll Surg 2014; 218(4):530-43.

Farney AC, Bering BJ, Nelson L, et al.(1998) No late failures of intraportal human islet autografts beyond 2 years. Transplantation Proc 1998; 30:420.

Health Quality Ontario.(2015) Pancreas islet transplantation for patients with type 1 diabetes mellitus: a clinical evidence review. Ont Health Technol Assess Ser. 2015;15(16):1-84. PMID 26644812

Robertson RP, Lanz KJ, Sutherland DE, et al.(2001) Prevention of diabetes for up to 13 years by auto islet transplantation after pancreatectomy for chronic pancreatitis. Diabetes 2001; 50(1):47-50.

U.S. Dept of Health and Human Services (HHS) Food and Drug Administration (FDA).(2009) Guidance for Industry: Considerations for Allogeneic Pancreatic Islet Cell Prodcuts. 2009; http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/CellularandGeneTherapy/UCM182441.pdf. Accessed April 17, 2015.

Wahoff DC, Papalois BE, Najarian JS, et al.(1995) Autologous islet transplantation to prevent diabetes after pancreatic resection. Ann Surg 1995; 222:562-579.

Wilson GC, Sutton JM, Abbott DE, et al.(2014) Long-term outcomes after total pancreatectomy and islet cell autotransplantation: is it a durable operation? Ann Surg. Oct 2014;260(4):659-665; discussion 665-657. PMID 25203883

Wu Q, Zhang M, Qin Y, et al.(2015) Systematic review and meta-analysis of islet autotransplantation after total pancreatectomy in chronic pancreatitis patients [Review]. Endocr J. Mar 30 2015;62(3):227-234. PMID 25735805


Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants or to the Tyson Group Health Plan participants.
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