Coverage Policy Manual
Policy #: 1998102
Category: Surgery
Initiated: August 2017
Last Review: April 2018
  Transplant, Allogeneic Islet Cell or Pancreas for Diabetes Mellitus

Description: Pancreas transplantation for treatment of insulin-dependent diabetes mellitus has been performed since the mid-1960’s.  The object of pancreas transplantation is to improve the life of the patient by making them insulin-independent, thus reducing the risks of complications from diabetes mellitus.  Pancreas transplant may be done simultaneously with kidney transplant for those patients who also are uremic, may be done after a period of time following a kidney transplant, or may be done unrelated to a kidney transplant.  The transplanted pancreatic tissue may come from a cadaver or a living donor.  Pancreas transplantation is considered to be an effective therapy for diabetes mellitus, and the potential complications from the surgery and risks of immunosuppression therapy are felt to be outweighed by the benefit of the transplant, although it is unknown if the mortality rate following transplantation is less than that inherent in a population of patients with 20 or more years of chronic diabetes who have extreme swings in glycemia, overt diabetic complications, and poor quality of life.

The American Diabetes Association has developed guidelines for pancreas transplantation.  This coverage policy for pancreas transplantation follows these guidelines.

Reimbursement for solid organ transplant (that has been pre-authorized if that is required) is made as a global fee limited to the lesser of billed charges or the average allowable charge authorized by the Blue Quality Centers for Transplant in the geographic region where the transplant is performed.  This global payment includes all related transplant services including institutional, professional, ancillary, and organ procurement.  The global period begins one day prior to the date of the transplant and continues for 23 days (for pancreas only) or 32 days (for a combination pancreas/kidney transplant) after the transplant.  This covers the inpatient/outpatient stay and provides a per diem outlier payment if necessary.  This global fee also includes the cost of complications arising from the original procedure when services are rendered within the global postoperative period for the particular transplant.

Coverage Policy #2003014, Transplant, Autologous Islet Cell for Chronic Pancreatitis, provides additional information.

Policy/
Coverage:
Pancreas transplantation meets primary coverage criteria for effectiveness and is covered in insulin dependent diabetic patients with imminent or established end-stage renal disease who have had or plan to have a kidney transplant, because the successful addition of a pancreas does not jeopardize patient survival, may improve kidney survival, and will restore normal glycemia.  Such patients also must meet the medical indications and criteria for kidney transplantation and not have excessive surgical risk for the dual transplant procedure.  The pancreas transplant may be done simultaneous with, or subsequent to, a kidney transplant.
 
In the absence of indications for kidney transplantation, pancreas transplantation is only covered for patients who meet the following three criteria:
    • A history of frequent, acute, and severe metabolic complications (hypoglycemia, hyperglycemia, ketoacidosis) requiring medical attention and documented in medical records;
    • Clinical and emotional problems with exogenous insulin therapy that are so severe as to be incapacitating; and
    • Consistent failure of insulin-based management to prevent acute complications.  
 
Pancreas retransplant following a failed primary transplant is covered one time only, as there is no information available that more than one transplant attempt following the primary transplant is successful.
 
Pancreatic islet cell transplants are considered investigational when done as an allogeneic transplant for a patient with diabetes mellitus.  Investigational services are an exclusion in the member certificate of coverage.
 
HCPCS codes G0341 (Percutaneous islet cell transplant, includes portal vein catheterization and infusion), G0342 (Laparoscopy for islet cell transplant, includes portal vein catheterization and infusion), and G0343 (Laparotomy for islet cell transplant, includes portal vein catheterization and infusion) were added effective October 1, 2004.  These codes are used to report Medicare services that are part of a clinical trial.  
 
CPT category III codes 0141T, 0142T, and 0143T became active CPT codes on 1/1/06.
 
Allogeneic islet cell transplantation is not covered based on benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
 
For contracts without primary coverage criteria, allogeneic islet cell transplantation is considered investigational.  Investigational services are an exclusion in the member benefit contract.

Rationale:
Pancreas After Kidney (PAK) Transplant
Based on current pancreas transplant registry data, at nearly 3 years, 64% of transplant recipients have a functioning pancreas compared to 77% among recipients of simultaneous pancreas and kidney transplants. PAK transplantation allows the uremic patient the benefits of a living-related kidney graft, if available, and the benefits of a subsequent pancreas transplant that is likely to result in improved quality of life compared to a kidney transplant alone. Uremic patients for whom a cadaveric kidney graft is available but a pancreas graft is not simultaneously available benefit similarly from a later pancreas transplant.
 
Pancreas Transplant Alone (PTA)
PTA graft survival has improved in recent years; available data suggest that 60% of grafts are functioning at 2 years, with potential insulin independence. In carefully selected IDDM patients with severely disabling and potentially life-threatening complications due to hypoglycemia unawareness and labile diabetes that persists despite optimal medical management, the benefits of PTA were judged to outweigh the risk of performing pancreas transplantation with subsequent immunosuppression. The majority of patients undergoing PTA are those with either hypoglycemic unawareness or labile diabetes. However, other exceptional circumstances may exist where nonuremic IDDM patients have significant morbidity risks due to secondary complications of diabetes (i.e., peripheral neuropathy) that exceed those of the transplant surgery and subsequent chronic immunosuppression. Because there is virtually no published evidence regarding outcomes of medical management in this very small group of exceptional diabetic patients, it is not possible to generalize about which circumstances represent appropriate indications for pancreas transplantation alone. Case-by-case consideration of each patient’s clinical situation may be the best option for determining the balance of risks and benefits.
 
Pancreas Retransplantation
For all three types of pancreas transplant (i.e., pancreas transplant alone, simultaneous pancreas kidney transplant, and pancreas after kidney transplant), the survival of a second pancreas transplant was lower than for the primary transplant of the same type. However, patients receiving second pancreas transplants have a good chance of remaining insulin-independent for 3 years or more.  There are inadequate data to permit scientific conclusion regarding the health outcomes associated with third or subsequent pancreas transplants.
 
Islet Cell Transplantation
Allogeneic islet cell transplantation to treat type 1 diabetes has been investigated for over 20 years.  Allograft survival had been universally poor until A.M.J. Shapiro at the University of Alberta in Edmonton, Canada, developed what is now called the “Edmonton Protocol”.  An international multi-center trial using that protocol in 36 patients (out of 2000 screened for eligibility) reported that 1) 44% of patients attained the stringent primary end point of insulin independence (defined as a glycated hemoglobin value of less than 6.5%, a glucose level after an overnight fast not exceeding 140 mg/dL more than 3 times per week, and a 2-hour postprandial glucose level not exceeding 180 mg/dL more than 4 times a week); 2) 28% of patients had partial graft function; 3) and 28% had complete graft loss.  Unfortunately, 76% became insulin dependent again by 2 years after transplantation.
 
Only 10% of another 65 patients transplanted by the Edmonton group with the same protocol have maintained insulin independence after 5 years.
 
The American Diabetes Association has provided the following recommendation regarding islet cell transplants: "Pancreatic islet transplants hold significant potential advantages over whole-gland transplants.  Recent strides have been made in improving the suces rates of this procedure.  However, at this time, islet trnasplantation is a rapidly evolving technology that also requires systemic immunosuppression and should be performed only within the setting of controlled research studies."  Clinical trials on the effectiveness of allogeneic islet cell transplants are ongoing.
 
2011 Update
A search of the MEDLINE database was conducted through January 2011.  A summary of the updated literature is provided.
 
Changes to the pancreas and kidney allocation system in 2010 may positively affect the availability of both organs for simultaneous kidney/pancreas transplant and therefore reduce the need for pancreas after kidney transplant considerations in diabetic uremic patients. The inferior graft survival rate in PAK, however, may be improved with current immunosuppressive regimens. In 2009, Fridell and colleagues reported a retrospective review (n=203) of a single center’s experience with PAK and SPK since 2003, when current induction/tacrolimus immunosuppressive strategies became standard (Fridell, 2009). Of the cases studied, 61 (30%) were PAK and 142 (70%) were SPK. One-year patient survival rates were 98% and 95% (PAK and SPK, respectively; p=0.44). Pancreas graft survival rates at one year were observed to be 95% and 90%, respectively (p=0.28). The authors conclude that in the modern immunosuppressive era, PAK should be considered as an acceptable alternative to SPK in candidates with an available living kidney donor.
 
Data that suggest that SPK transplants have a higher overall graft survival rate than PAK, including kidney graft survival, has led to the question of whether kidney transplant alone (KTA) is superior to PAK. In 2009, Kleinclauss and colleagues retrospectively examined data from diabetic kidney transplant recipients (n=307) from a single center and compared renal graft survival rates in those who subsequently received a pancreatic transplant to those who did not (Kleinclauss, 2009). The comparative group was analyzed separately depending on whether they were medically eligible (KTA-E) for pancreas transplant, but chose not to proceed for financial or personal reasons, or were ineligible (KTA-I) for medical reasons. The KTA-I (n=57) group differed significantly at baseline from both the PAK group (n=175) and the KTA-E group (n=75) with respect to age, type of diabetes and dialysis experience; kidney graft survival rates were lower than either of the other groups, with one, five and 10-years rates of 75%, 54% and 22%, respectively (p<0.0001). The PAK and KTA-E groups were similar in age, race, type of diabetes, and dialysis experience. The authors compared one-, five- and ten-year kidney graft survival rates in PAK patients with those in the KTA-E group: 98%, 82% and 67% versus 100%, 84% and 62%, respectively, and concluded that the subsequent transplant of a pancreas after a living donor kidney transplant does not adversely affect patient or kidney graft survival rates.
 
The Pancreas Allotransplantation for Diabetic Nephropathy and Mild Chronic REnal fAilure Stage (PANCREAS) Study (NCT01067950) is currently recruiting participants at Nantes University in France. The stated objective of the study is to assess the superiority of isolated pancreas transplant to intensive insulin therapy in Type 1 diabetes patients with overt proteinuric nephropathy and mildly reduced renal function. This is to be an open-label, randomized trial. The primary combined endpoint is to be patient mortality and renal function impairment at five years. Secondary endpoints measuring safety and extrarenal diabetic complications are planned. If completed, this would represent the first RCT comparing pancreas transplant to insulin therapy.
 
In 2010, Mora and colleagues described the long-term outcome of 12 patients 15 years following simultaneous pancreas/kidney transplant (Mora, 2010). Metabolic measures of glucose control were measured at one, five, ten and 15 years following the procedure. Of this subset of patients, six (50%) had non-diabetic glucose challenge tests. Basal serum insulin levels declined over this period as well, from 24 mU/L to 16 mU/L at one and 15 years, respectively. The authors conclude that in a select group of patients whose pancreatic graft continued to function after 15 years, some glycemic control continued, albeit in a diminished fashion. It should be noted that this represents a small fraction of the 367 patients receiving the simultaneous pancreas/kidney transplant at this single center (12 of 367 SPK; 3.3%). The number of allograft survivals at five or more, and 10 or more years in this study was 43 (11.7%) and 28 (7.6%), respectively.
 
In 2009, Isla Pera and colleagues described the results of an observational quality of life (QoL) study in Spanish patients following SPK transplant (Isla Pera, 2009). Data on quality of life is particularly important in this patient population, due to the fact that alternatives to transplant exist, and quality of life post-transplant must be balanced by the harms introduced by lifelong immunosuppressive therapy. The Short Form health Survey 36-Item (SF-36) was administered to 69 SPK transplant recipients and 34 patients with Type 1 diabetes on hemodialysis. They also compared the transplant QoL results to a reference Spanish population. The authors attempted to control for group differences with multivariate analysis on variables of age, sex, and years duration of diabetes diagnosis. While SPK patients had lower QoL compared to the reference population across all eight domains of physical and mental well-being, they had a statistically significant higher score across these same domains in comparison to diabetic patients on dialysis. No aggregate measures were reported. Findings in a healthcare system outside the United States may not apply to U.S. populations.
 
The literature, consisting primarily of case series and registry data, demonstrate graft survival rates comparable to other solid organ transplants, as well as attendant risks associated with the immunosuppressive therapy necessary to prevent allograft rejection. No randomized controlled trials (RCTs) compare any form of pancreas transplant to insulin therapy; the PANCREAS trial (NCT01067950) is currently recruiting patients to compare isolated pancreas transplant to intensive insulin therapy in nonuremic diabetics with poorly controlled diabetes.  There was no literature identified in this policy update that would prompt a change in the coverage statement.
 
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.
 
Pancreatic transplant
Several 2011 studies addressed pancreas transplantation in individuals 50 years of age or older. A study by Afaneh and colleagues reviewed data on 17 individuals at least 50-years-old and 119 individuals younger than 50 who had a pancreas transplant at a single institution in the U.S (Afaneh, 2011). The 2 groups had similar rates of surgical complications, acute rejection and non-surgical infections. Overall patient survival was similar. Three- and 5-year survival rates were 93% and 90% in the younger group and 92% and 82% in the older group. Schenker and colleagues in Germany compared outcomes in 69 individuals at least 50-years-old and 329 individuals younger than 50 years who had received a pancreas transplant (Schenker, 2011). Mean duration of follow-up was 7.7 years. One-, 5-, and 10-year patient and graft survival rates were similar in the 2 groups. For example, the 5-year patient survival rate was 89% in both groups. The 5-year pancreas grant survival rate was 76% in the older group and 72% in the younger group. The authors of both studies, as well as the authors of a commentary accompanying the Schenker article, (Gruessner, 2011) agreed that individuals age 50 years and older are suitable candidates for pancreas transplantation.
 
Islet transplant
In 2011, Thompson and colleagues in Canada published findings from a prospective cross-over study of intensive medical therapy (pretransplant) versus islet cell transplantation in patients with type 1 diabetes (Thompson, 2011). The article reported on 45 patients; at the time of data analysis, 32 had received islet cell transplants. Eight of 45 (18%) patients were no longer being followed; 5 dropped out pretransplant and 3 post-transplant. Two were lost to follow-up, 1 withdrew after graft failure, 2 withdrew due to persistent fatigue, 2 developed malignancy, and 1 had a severe CMV infection. Primary outcome measures are HbA1c, change in glomerular filtration rate (GFR), progression of retinopathy, and change in nerve conduction velocity. Median follow-up was 47 months pre-transplant and 66 months post-transplant. The overall mean HbA1c was 7.8% pretransplant and 6.7% post-transplant; this difference was statistically significant, p<0.001. In the 16 patients for whom sufficient data pre- and post-transplant were available on renal outcomes, the median decline in GFR (mL/min/month) was -6.7 pretransplant and -1.3 post-transplant (p=0.01). Retinopathy was assessed using the International Scale which categorizes nonproliferative diabetic retinopathy as mild, moderate, or severe. Retinopathy progressed in 10 of 82 (12%) eyes pretransplant versus 0 of 51 post-transplant (p<0.01). (The numbers of patients in the retinopathy analyses was not reported). The rate of change in nerve conduction velocity did not differ significantly between groups (exact numbers not reported). The authors noted that their finding of reduced microvascular complications after islet transplantation may be due, in part, to their choice of maintenance immunosuppression. The study used a combination of tacrolimus and mycophenolate mofetil (MMF). Additional studies with larger numbers of patients are needed to confirm the impact of islet transplantation on microvascular complications and the optimal immunosuppression regimen.
 
2013 Update
A literature search conducted through June 2013 did not reveal any new information that would prompt a change in the coverage statement.
 
Pancreas Retransplant
In 2013, Buron and colleagues reported on their experience with pancreas retransplantation in France and Geneva (Buron, 2013).  Between 1976 and 2008, 568 pancreas transplants were performed at 2 centers, including 37 repeat transplants. Patient survival after a repeat pancreas transplant was 100% after 1 year and 89% after 5 years. Graft survival was 64% at 1 year and 46% at 5 years. Among the 17 patients who underwent a second transplant in a later time period i.e., between 1995 and 2007, graft survival was 71% at 1 year and 59% at 5 years. In this more recently transplanted group, graft survival rates were similar to primary pancreas transplants, which was 79% at 1 year and 69% at 5 years.
 
Allogeneic Islet Cell Transplantation
In 2008 a report was published from the Collaborative Islet Transplant Registry (CITR), which collects and monitors data on allogeneic islet transplantation in North America, Europe, and Australia, had 325 adult recipients in their registry as of April 2008 (Alejandro, 2008). Three years after first infusion, 23% of islet-alone recipients were insulin-independent (defined as insulin-independent 2 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, 71% of whom were still insulin-independent 1 year later and 52% at 2 years. Factors that favored primary outcomes were higher number of islet infusions, greater number of total islet equivalents infused, lower pretransplant HbA1c levels, processing centers related to the transplant center, and larger islet size.
 
The CITR published an updated report in 2012; the focus of the article was changes in outcomes over time (Barton, 2012). The number of patients receiving islet transplants was 214 during 1999-2002, 255 between mid-2003-2006 and 208 from 2007-2010. A total of 575 of the 677 (85%) islet transplant recipients received islets only; the remainder underwent simultaneous kidney and islet transplants. In the 1999-2002 group, rates of insulin independence were 51% after 1 year, 36% after 2 years and 27% after 3 years. Rates for the 2007-2010 group were 66%, 55% and 44%, respectively. The incidence of clinically reportable adverse events in the first year after infusion decreased from 50-53% in 1999-2006 to 38% in 2007-2010. The rates of peritoneal hemorrhage or gallbladder infusion were 5.4% in 1999-2003 and 3.1% in 2007-2010. The authors did not report findings separately for the subset of patients who underwent islet-only transplants.
 
In 2012, Vantyghem and colleagues reported on 23 patients with type 1 diabetes who underwent islet transplantation; 14 had islet-only transplants and 9 had islet after kidney transplants (Vantyghem, 2012). Median HbA1c was 8.3% at baseline and 6.7% at 3 years. Ten of the 23 patients (43%) were insulin independent 3 years after islet transplantation. Findings were not reported separately for the islet-only transplant recipients.
 
Ongoing Clinical Trials
A comparison of strict glucose control with usual care at the time of islet cell transplantation (NCT01123122) : This is a single-center randomized controlled trial (RCT) comparing the impact of strict glucose control versus usual care prior to islet cell transplantation on outcomes in patients with type 1 diabetes. The primary study outcome is islet cell function 3 months post-transplantation. The estimated enrollment is 32 patients, and the estimated study completion date is September 2015
 
A comparison of islet cell transplantation with medical therapy on the risk of progression of diabetic retinopathy and diabetic macular edema (NCT00853424) :
 This RCT is comparing islet cell transplantation to standard medical therapy in patients with diabetic eye disease. The primary outcome is progression of diabetic retinopathy or moderate visual loss. The estimated enrollment is 40 patients, and the estimated study completion date is June 2015.
 
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.
 
Several case series have been published. These series tend to have small sample sizes and relatively short-term follow-up. Representative series are described next.
 
In 2013, Rickels et al reported on 12 patients with type 1 diabetes and severe hypoglycemia who had islet transplantation (Rickels, 2013). Mean glycosylated hemoglobin decreased from 7.0%±0.3% before the procedure to 5.6%±0.1% after 6 to 7 months (p<0.01). All of the insulin sensitivity measures were significantly less than normal before islet transplantation and not significantly different from normal after transplantation. Adverse events were not discussed.
 
In 2013, O’Connell et al reported on 17 patients with type 1 diabetes and severe hypoglycemia who underwent islet transplantation in Australia (O’Connell, 2013). The primary end point was the proportion of patients who had had an HbA1c less than 7% and no severe hypoglycemic events 2 months after the initial transplant. (Patients could have 1 or 2 infusions.) Fourteen of the 17 (82%) patients achieved the primary end point. Nine (53%) patients attained insulin independence for a median of 26 months. At the time of data analysis for this publication, 6 patients remained insulin independent. Most adverse events related to immunosuppression. Seven of the 17 (41%) patients developed mild lymphopenia and 1 developed Clostridium difficile colitis; these all responded to treatment. Eight patients developed anemia shortly after transplant and 1 required a blood transfusion. Procedure-related complications included 1 partial portal vein thrombosis and 3 postoperative bleeds; 2 of the bleeds required transfusion. Patients were followed for different amounts of time; long-term follow-up data were not available for a consistent length of time.
 
Trial Comparing Metabolic Efficiency of Islet Graft to Intensive Insulin Therapy for Type 1 Diabetes's Treatment (TRIMECO) (NCT01148680): This randomized controlled trial is comparing islet transplantation to intensive insulin therapy in patients with type 1 diabetes. The estimated enrollment is 40 patients, and the estimated study completion date is December 2014.
 
The techniques for allogeneic islet cell transplants are evolving, and the impact on the net health outcome is still uncertain. Moreover, longer follow-up with larger numbers of patients is needed before conclusions can be drawn about the safety of allogeneic islet transplantation and its impact on diabetes mellitus and associated complications. Thus, this technology is considered investigational for patients with diabetes type 1.
  
2015 Update
 
A literature search conducted through February 2015 did not reveal any new information that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
Several centers have published outcomes after pancreas retransplantation. In 2014, Seal and colleagues reported on 96 consecutive PTA patients treated at a single center in Canada; 78 were initial transplants, and 18 were retransplants (Seal, 2014). Pancreas graft survival was similar for primary transplants and retransplants at 1year (88% vs 100%, p=0.88) and 3 years (85% in both groups, p=0.99). Patient survival rates were also similar in the 2 groups at 1 year (96% and 100%, p=0.95) and 3 years (93% and 100%, p=0.93).
 
Recipient age over 50 years has in the past been considered a relative contraindication for pancreas transplant. In the past 5 to 10 years, several analyses of outcomes by patient age group have been published and there is now general agreement among experts that age should not be a contraindication; however, age-related comorbidities are important to consider when selecting patients for transplantation. In the largest study of pancreas outcomes by recipient age, Siskind and colleagues used data from the UNOS database (Siskind, 2014).Investigators included all adult patients who received SPK or PTA between 1996 and 2012 (n=20,854). There were 3160 patients between the ages of 50 and 59 years, and 280 patients age 60 or older. Overall, Kaplan-Meier survival analysis found statistically significant differences in patient survival (p<0.001) and graft survival (p<0.001) among age categories. Graft survival was lowest in the 18- to-29 age group at 1, 5, and 10 years, which the authors noted might be due to early immunological graft rejection due to more robust immune responses. However, 10 and 15 year graft survival was lowest in the 60 and older age group. Patient survival rates decreased with increasing age, and the differential between survival in older and younger ages increased with longer follow-up intervals. Lower survival rates in patients 50 and older could be due in part to comorbidities at the time of transplantation. Also, as patient age, they are more likely to die from other causes. Still, patient survival at 5 and 10 years was relatively high.
 
In 2014, the Board of Directors of the Organ Procurement and Transplantation Network issued an updated comprehensive list of transplant related policies (OPTN, 2014). Each candidate registered on the pancreas waiting list must meet one of the following requirements:
  • Be diagnosed with diabetes
  • Have pancreatic exocrine insufficiency
  • Require the procurement or transplantation of a pancreas as part of a multiple organ transplant for technical reasons
 
The policy also delineated pancreas, kidney-pancreas, and islet allocation, classifications, and rankings.
 
2018 Update
Annual policy review completed with a literature search using the MEDLINE database through March 2018. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
A systematic review by Health Quality Ontario in 2015 reported on islet transplantation for patients with type 1 diabetes (Health Quality Ontario, 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.
 
ONGOING AND UNPUBLISHED CLINICAL TRIALS
Some currently unpublished trials that might influence this review are listed below.
 
NCT00679042  Islet Transplantation in Type 1 Diabetic Patients Using the University of Illinois at Chicago (UIC) Protocol
Expected Enrollment: 1000
Completion Date: Sep 2017
 
NCT00706420 Islet Transplantation Alone (ITA) in Patients With Difficult to Control Type I Diabetes Mellitus Using a Glucocorticoid-free Immunosuppressive Regimen
Expected Enrollment: 20
Completion Date: May 2018
 
NCT02505893 Minimal Islet Transplant at Diabetes Onset (MITO)
Expected Enrollment: 6
Completion Date: May 2018
 
NCT00160732 Allogenic Islet Cell Transplantation
Expected Enrollment: 50
Completion Date: Oct 2018
 
NCT01897688 A Phase 3 Single Center Study of Islet Transplantation in Nonuremic Diabetic Patients
Expected Enrollment: 20
Completion Date: Dec 2018
 
NCT00306098 Islet Cell Transplantation Alone in Patients With Type 1 Diabetes Mellitus: Steroid-Free Immunosuppression
Expected Enrollment: 40
Completion Date: May 2019
 
NCT01909245 Islet Cell Transplant for Type 1 Diabetes (TCD)
Expected Enrollment: 30
Completion Date: Jul 2021
 
 
NCT01974674 Allogeneic Islet Transplantation for the Treatment of Type 1 Diabetes (GRIIF)
Expected Enrollment: 19
Completion Date: Jan 2022  

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: Adang EM, Engel GL, van Hooff JP, et al.(1996) Comparison before and after transplantation of pancreas kidney and pancreas-kidney with loss of pancreas—a prospective controlled quality of life study. Transplantation 1996; 62:754-758.

Afaneh C, Rich BS, Aull MJ et al.(2011) Pancreas transplantation: does age increase mortality? J Transplant 2011 [Epub before print].

Alejandro R, Barton FB, Hering BJ et al.(2008) 2008 Update from the Collaborative Islet Transplant Registry. Transplantation 2008; 86(12):1783-8.

Allen RD, Al-Harbi IS, Morris JG, et al.(1997) Diabetic neuropathy after pancreas transplantation: determinants of recovery. Transplantation 1997; 63:830-838.

Andersson DKG, et al.(1993) Implications of the Diabetes Control and Complications. Trial American Diabetes Association. Diabetes Care 1993; 16:1517-20.

Bartlett ST, Schweitzer EJ, Johnson LB, et al.(1996) Equivalent success of simultaneous pancreas kidney and solitary pancreas transplantation. Ann Surg 1996; 224:440-452.

Barton FB, Rickels MR, Alejandro R et al.(2012) Improvement in outcomes of clinical islet transplantation: 1999-2010. Diabetes Care 2012; 35(7):1436-45.

Basadonna GP, Arrazola L, Matas AJ, et al.(1993) Morbidity, mortality, and long-term allograft function in kidney transplantation alone and simultaneous pancreas kidney in diabetic patients. Trans Proc 1993; 25:1321-1322.

Benedetti E, Gruessner AC, Troppmann C, et al.(1996) Intra-abdominal fungal infections after pancreatic transplantation: Incidence, treatment, and outcome. J Am Col Surg 1996; 183:307-316.

Bromberg JS, LeRoth D.(2006) Diabetes cure - Is the glass half full? New Engl J Med, 2006; 355:1372-1374.

Buron F, Thaunat O, Demuylder-Mischler S et al.(2013) Pancreas Retransplantation: A Second Chance for Diabetic Patients? Transplantation 2013; 95(2):347-52.

Caldara R, Bandello F, Vigano C, et al.(1994) Influence of successful pancreaticorenal transplantation on diabetic retinopathy. Trans Proc 1994; 26:490.

Cheung AHS, Matas AJ, Gruessner RG, et al.(1993) Should uremic diabetic patients who want a pancreas transplant receive a simultaneous cadaver kidney-pancreas transplant or a pancreas transplant? Trans Proc 1993; 25:1184-5.

Cheung AHS, Sutherland DER, Dunn DL, et al.(1992) Morbidity following simultaneous pancreas-kidney transplants vs kidney transplants alone in diabetic patients. Trans Proc 1992; 24:866-8.

Clinical Trial Registry of the U. S. National Institutes of Health. Pancreas Allotransplantation for Diabetic Nephropathy and Mild Chronic REnal fAilure Stage (PANCREAS) trial. Available online at: http://clinicaltrials.gov/ct2/show/NCT01067950?term=pancreas+transplant&rank=4. Last accessed January 26, 2011.

Cranston I, Lomas J, Maran A, et al.(1994) Restoration of hypoglycemia awareness in patients with long-duration insulin-dependent diabetes. Lancet 1994; 344:283-287.

Dagogo-Jack S, Rattarasarn C, Cryer PE.(1994) Reversal of hypoglycemia unawareness, but not defective glucose counter regulation, in IDDM. Diabetes 1994; 43:1426-34.

Eisenbarth GS, Stegall M.(1996) Islet and pancreatic transplantation—autoimmunity and alloimmunity. NEJM 1996; 335:888-890. [Editorial].

Ericzon BG, Groth CG, Bismuth A, et al.(1994) Glucose metabolism in liver transplant recipients treated with FK 506 or cyclosporin in the European multicenter study. Trans Int 1994; 7(sup 1):11-14.

Fioretto P, Mauer SM, Bilous RW, et al.(1993) Effects of pancreas transplantation on glomerular structure in insulin dependent diabetic patients with their own kidneys. Lancet 1993; 342:1193-1196.

Fioretto P, Steffes MW, Mihatsch MJ, et al.(1995) Cyclosporine associated lesions in native kidneys of diabetic pancreas transplant recipients. Kidney Int 1995; 48:489-495.

Foger B, Konigsrainer A, Palos G, et al.(1994) Effect of pancreas transplantation on lipoprotein lipase, postprandial lipemia, and HDL cholesterol. Transplantation 1994; 58:899-904.

Fridell JA, Mangus RS, Hollinger EF et al.(2009) The case for pancreas after kidney transplantation. Clin Transplant 2009; 23(4):447-53.

Gaber AO, El-Gebely S, Sugathan P, et al.(1995) Changes in cardiac function of Type I diabetics following pancreas-kidney and kidney-alone transplantation. Trans Proc 1995; 27:1322-1323.

Gaber AO, Hathaway DK, Abell T, et al.(1994) Improved autonomic and gastric function in pancreas kidney vs kidney-alone transplantation contributes to quality of life. Trans Proc 1994; 26:515-516.

Gross CR, Zehrer CL.(1993) Impact of the addition of a pancreas to quality of life in uremic diabetic recipients of kidney transplants. Trans Proc 1993; 25:1293-5.

Gruessner A, Gruessner R, Moudry-Munns K, et al.(1993) Influence of multiple factors (age, transplant number, recipient category, donor source) on outcome of pancreas transplantation at one institution. Trans Proc 1993; 25:1303-5.

Gruessner AC, Sutherland DE, Gruessner RW.(2012) Long-term outcome after pancreas transplantation. Curr Opin Organ Transplant 2012; 17(1):100-5.

Gruessner AC, Sutherland DE.(2011) Access to pancreas transplantation should not be restricted because of age. Transplant Int 2011; 24(2):134-35.

Gruessner AC.(2011) 2011 update on pancreas transplantation: Comprehensive trend analysis of 25,000 cases followed up over the course of twenty-four years at the International Pancreas Transplant Registry. Rev Diabet Stud 2011; 8(1):6-16.

Gruessner RW, Sutherland DE, Gruessner RW.(1997) Solitary pancreas transplants: improving results and factors that influence outcome. Trans Proc 1997; 29:664-665.

Gruessner RW, Sutherland DE, Troppmann C, et al.(1997) The surgical risk of pancreas transplantation in the cyclosporine era: An overview. J Am Col Surg 1997; 185:128-144.

Gruessner RW.(1997) Tacrolimus in pancreas transplantation: a multicenter analysis. Clin Trans 1997; 11:299-312.

Hariharan S, Peddi VR, Munda R, et al.(1997) Long term renal and pancreas function with tacrolimus rescue therapy following kidney/pancreas transplantation. Trans Proc 1997; 29:652-653.

Hathaway D, Abell T, Cardoso S, et al.(1993) Improvement in autonomic function following pancreas-kidney versus kidney-alone transplantation. Trans Proc 1993; 25:1306-8.

Hathaway DK, Hartwig MS, Milstead J, et al.(1994) Improvement in quality of life reported by diabetic recipients of kidney-only and pancreas-kidney allografts. Trans Proc 1994; 26:512-514.

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

Henley SE, Larsen JL, Mack-Shipman L, et al.(1995) Lipids following pancreas transplantation in recipients receiving FK 506. Trans Proc 1995; 27:2997.

Hickey DP, Bakthavatsalam R, Bannon CA, et al.(1997) Urological complications of pancreatic transplantation. J Urol 1997; 157:2042-2048.

Hricik DE, Phinney MS, Weigel KA, et al.(1997) Long term renal function in Type I diabetics after kidney or kidney-pancreas transplantation. Transplantation 1997; 64:1283-1288.

Hughes TA, Gaber O, Amiri HS, et al.(1994) Lipoprotein composition in insulin-dependent diabetes mellitus with chronic renal failure: Effect of kidney and pancreas transplantation. Metabolism 1994; 43:333-347.

Isla Pera P, Moncho Vasallo J, Torras Rabasa A et al.(2009) Quality of life in simultaneous pancreas-kidney transplant recipients. Clin Transplant 2009; 23(5):600-5.

Katz HH, Nguyen TT, Velosa JA, et al.(1994) Effects of systemic delivery of insulin on plasma lipids and lipoprotein concentrations in pancreas transplant recipients. Mayo Clin Proc 1994; 29:231-236.

Kendall DM, Rooney DP, Smets YFC, et al.(1997) Pancreas transplantation restores epinephrine response and symptom recognition during hypoglycemia in patients with long-standing type I diabetes and autonomic neuropathy. Diabetes 1997; 46:249-57.

Ketel BL, Turton-Weeks S, Reed K, et al.(1996) Tacrolimus-based vs cyclosporine-based immunotherapy in combined kidney-pancreas transplantation. Trans Proc 1996; 28:899.

Kiebert GM, van Oosterhout EC, van Bronswijk H, et al.(1994) Quality of life after combined kidney-pancreas or kidney transplantation in diabetic patients with end-stage renal disease. Clin Trans 1994; 8:239-245.

Kleinclauss F, Fauda M, Sutherland DE et al.(2009) Pancreas after living donor kidney transplants in diabetic patients: impact on long-term kidney graft function. Clin Transplant 2009; 23(4):437-46.

Laftavi MR, Chapuis F, Vial C, et al.(1995) Diabetic polyneuropathy outcome after successful pancreas transplantation: 1 to 9 year follow up. Trans Proc 1995; 27:1406-1409.

Landgraf R.(1996) Impact of pancreas transplantation on diabetic secondary complications and quality of life. Diabetologia 1996; 39:1415-1424.

Larsen JL, Stratta RJ.(1996) Pancreas transplantation: A treatment option for insulin-dependent diabetes mellitus. Diabetes Metab 1996; 22:139-146.

Lenisa L, Castoldi R, Socci C, et al.(1995) Cost-effective treatment for diabetic end-stage renal disease: Dialysis, kidney, or kidney-pancreas transplantation. Trans Proc 1995; 27:3108-3113.

Milde FK, Hart LK, Zehr PS.(1992) Quality of life of pancreatic transplant recipients. Diabetes Care 1992; 15:1459-63.

Mora M, Ricart MJ, Casamitjana R et al.(2010) Pancreas and kidney transplantation: long-term endocrine function. Clin Transplant 2010; 24(6):E236-40.

Morrissey PE, Shaffer D, Madras PN, et al.(1997) Progression of peripheral vascular disease after combined kidney-pancreas transplantation in diabetic patients with end-stage renal failure. Trans Proc 1997; 29:662-663.

Moudry-Munns KC, Gruessner A, Sutherland DER.(1993) Analysis of United States Pancreas Transplant Registry data. Clin Trans 1993.

Nakache R, Tyden G, Groth CG.(1994) Long-term quality of life in diabetic patients after combined pancreas- kidney transplantation or kidney transplantation. Trans Proc 1994; 26:510-511.

Nankivell BJ, Chapman JR, Bovington KJ, et al.(1996) Clinical determinants of glucose homeostasis after pancreas transplantation. Transplantation 1996; 61:1705-1711.

Navarro X, Sutherland DE, Kennedy WR.(1997) Long term effects of pancreatic transplantation on diabetic neuropathy. Ann Neurol 1997; 42:727-736.

NCT00853424. Sponsored by University of British Columbia.(2013) A Comparison of Islet Cell Transplantation With Medical Therapy on the Risk of Progression of Diabetic Retinopathy and Diabetic Macular Edema. Available online at: www.clinicaltrials.gov. Last accessed April, 2013.

O'Connell PJ, Holmes-Walker DJ, Goodman D et al.(2013) Multicenter Australian trial of islet transplantation: improving accessibility and outcomes. Am J Transplant 2013; 13(7):1850-8.

Organ Procurement and Transplantation Network (OPTN). Policies and Bylaws: Deceased Donor Organ Procurement http://optn.transplant.hrsa.gov/PoliciesandBylaws2/policies/pdfs/policy_7.pdf. Accessed December 1, 2014

Pancreas Retransplantation. 2001 Blue Cross Blue Shield Association Technology Evaluation Center Assessment.

Pancreas Transplantation. 1998 Blue Cross Blue Shield Association Technology Evaluation Center Assessment.

Papalois BE, Troppmann C, Gruessner AC, et al.(1996) Long-term peritoneal dialysis before transplantation and intra-abdominal infection after simultaneous pancreas kidney transplantations. Arch Surg 1996; 131:761-766.

Pelletier RP, Elkhammas EA, Henry ML, et al.(1996) Update on the status of pancreas-kidney transplantation. Curr Opin Nephrol Hypertens 1996; 5:504-507.

Piehlmeier W, Bullinger M, Kirchberger I, et al.(1994) Prospective study of the quality of life in Type I diabetic patients before and after organ transplantation. Trans Proc 1994; 26:522-523.

Pirsch JD, Andrews C, Hricik DE, et al.(1996) Pancreas transplantation for diabetes mellitus. Am J Kidney Dis 1996; 27:444-450.

Rickels MR, Kong SM, Fuller C et al.(2013) Improvement in insulin sensitivity after human islet transplantation for type 1 diabetes. J Clin Endocrinol Metab 2013; 98(11):E1780-5.

Roberson RP, Latsen J, Davis C, et al.(2001) Pancreas transplantation for patients with type 1 diabetes. American Diabetes Association: Clinical Practice Recommendations. Diabetes Care 2001; 24 (sup 1).

Robertson RP, Davis C, Larsen J, et al.(2000) Pancreas and islet transplantation for patients with diabetes mellitus. Diabetes Care 2000; 23:112-116.

Robertson RP, Sutherland DE, Kendall DM, et al.(1996) Metabolic characterization of long-term successful pancreas transplants in Type I diabetes. J Invest Med 1996; 44:549-555.

Ryan EA, Paty BW, Senior PA, et al.(2005) Five year follow-up after clinical islet transplantation. Diabetes, 2005; 54:2060-2069.

Schenker P, Vonend O, Kruger B et al.(2011) Long-term results of pancreas transplantation in patients older than 50 years. Transplant Int 2011; 24(2):136-42.

Schulack JA, Mayes JT, Hricik DE.(1992) Kidney transplantation in diabetic patients undergoing combined kidney-pancreas or kidney-only transplantation. Transplantation 1992; 53:685-687.

Seal J, Selzner M, Laurence J, et al.(2014) Outcomes of Pancreas Retransplantation After Simultaneous Kidney-Pancreas Transplantation Are Comparable to Pancreas After Kidney Transplantation Alone. Transplantation. Aug 21 2014. PMID 25148379

Shapiro AJM, Ricordi C, Hering BJ, et al.(2006) International trial of the Edmonton protocol for islet transplantation. New Engl J Med, 2006;355:1318-1330.

Siskind E, Maloney C, Akerman M, et al.(2014) An analysis of pancreas transplantation outcomes based on age groupings--an update of the UNOS database. Clin Transplant. Sep 2014;28(9):990-994. PMID 24954160

Solders G, Tyden G, Persson A, et al.(1992) Improvement of nerve conduction in diabetic neuropathy: a follow-up study 4 yr after combined pancreatic and renal transplantation. Diabetes 1992; 41:946-51.

Sponsored by Vancouver Coastal Health.(2013) A comparison of strict glucose control with usual care at the time of islet cell transplantation. NCT01123122. Sponsored by Vancouver Coastal Health. Available online at: www.clinicaltrials.gov. Last accessed April, 2013.

Stegall MD, Ploeg RJ, Pirsch JD, et al.(1993) Living related kidney transplant or simultaneous pancreas-kidney for diabetic renal failure. Trans Proc 1993; 25:230-232.

Stratta RJ, Lowell JA, Sudan D, et al.(1997) Retransplantation in the diabetic patient with a pancreas allograft. Am J Surg 1997; 174:759-763.

Stratta RJ, Taylor RJ, Bynon JS, et al.(1994) Surgical treatment of diabetes mellitus with pancreas transplantation. Ann Surg 1994; 220:809-817.

Stratta RJ, Taylor RJ, Ozaki CF, et al.(1993) Combined pancreas-kidney transplantation versus kidney transplantation alone: analysis of benefit and risk. Trans Proc 1993; 25:1298-1301.

Stratta RJ, Taylor RJ, Sindhi R, et al.(1996) Analysis of early readmissions after combined pancreas kidney transplantation. Am J Kidney Dis 1996; 28:867-877.

Stratta RJ, Weide LG, Sindhi R, et al.(1997) Solitary pancreas transplantation: Experience with 62 consecutive cases. Diabetes Care 1997;20:362-368.

Sutherland DE, Gruessner AC, Moudry-Munns KC, et al.(1993) Tabulation of cases from the International Pancreas Transplant Registry and analysis of United Network for Organ Sharing United States Pancreas Transplant Registry data according to multiple variables. Trans Proc 1993; 25:1707.

Sutherland DE.(1994) Present status of pancreas transplantation alone in nonuremic diabetic patients. Trans Proc 1994; 26:379-383.

Sutherland DER, Goren PF, Farney AC, et al.(1993) Evolution of kidney, pancreas, and islet transplantation for patients with diabetes at the University of Minnesota. Am J Surg 1993; 166:456-91.

Sutherland DER, Rainer WG, Dunn DL, et al.(2001) Lessons learned from more than 1,000 pancreas transplants at a single institution. Ann Surg 2001; 233:463-50.

Thompson DM, Meloche M, Ao Z et al.(2011) Reduced progression of diabetic microvascular complications with islet cell transplantation compared with intensive medical therapy. Transplantation 2011; 91(3):373-8.

Tibell A, Solders G, Larsson M, et al.(1997) Superior survival after simultaneous pancreas and kidney transplantation compared with transplantation of a kidney alone in diabetic recipients followed for 8 years. Trans Proc 1997; 29:668.

Troppmann C, Gruessner AC, Benedetti E, et al.(1996) Vascular graft thrombosis after pancreatic transplantation: Univariate and multivariate operative and nonoperative risk factor analysis. J Am Col Surg 1996; 182:285-316.

Tyden G, Reinholt FP, Sundkvist G, et al.(1996) Recurrence of autoimmune diabetes mellitus in recipients of cadaveric pancreatic grafts. NEJM 1996; 335:888-890.

Vantyghem MC, Raverdy V, Balavoine AS et al.(2012) Continuous glucose monitoring after islet transplantation in type 1 diabetes: an excellent graft function (beta-score greater than 7) Is required to abrogate hyperglycemia, whereas a minimal function is necessary to suppress severe hypoglycemia (beta-score greater than 3). J Clin Endocrinol Metab 2012; 97(11):E2078-83.

Zehrer CL, Gross CR.(1994) Patient perceptions of benefits and concerns following pancreas transplantation. Diabetes Educ 1994; 20:216-220.


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.
CPT Codes Copyright © 2019 American Medical Association.