Medical Policy: 07.03.09
Original Effective Date: November 2009
Reviewed: October 2018
Revised: October 2018
Benefit determinations are based on the applicable contract language in effect at the time the services were rendered. Exclusions, limitations or exceptions may apply. Benefits may vary based on contract, and individual member benefits must be verified. Wellmark determines medical necessity only if the benefit exists and no contract exclusions are applicable. This medical policy may not apply to FEP. Benefits are determined by the Federal Employee Program.
This Medical Policy document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy will be reviewed regularly and be updated as scientific and medical literature becomes available.
Achievement of insulin dependence with resultant decreased morbidity and increased quality of life is the primary health outcome of pancreas transplantation. Transplantation of the pancreas is a treatment method for patients with insulin dependent diabetes mellitus. Pancreas transplantation can restore glucose control and is intended to prevent, halt or reverse the secondary complications from diabetes mellitus. While pancreas transplantation is generally not considered a life-saving treatment, in a small subset of patients who experience life-threatening complications from diabetes, pancreas transplantation could be considered life-saving.
Pancreas transplantation occurs in several different scenarios such as:
The pancreas transplant may involve either the whole pancreas or a pancreas segment. Whole organ transplantation are far more common but a segmental transplant is possible. Segmental transplants are done if a living donor is involved (Organ Procurement and Transplantation Network 2018).
Most patients undergoing pancreas transplant alone (PTA) are those with either hypoglycemic unawareness or labile diabetes. However, other exceptional circumstances may exist where nonuremic type I diabetes patients have significant morbidity risks due to secondary complications of diabetes that exceed those of the transplant surgery and subsequent chronic immunosuppression. Because virtually no published evidence addresses outcomes of medical management in this very small group of diabetic patients, is not possible to generalize about which circumstances represent appropriate indications for PTA. Case-by-case consideration of each patient’s clinical situation may be the best option for determining the balance of risks and benefits. The purpose of PTA is to restore glucose control and is intended to prevent, halt or reverse the secondary complications from diabetes such as retinopathy, neuropathy, or end-stage renal disease.
Pancreas transplant is not typically used for the treatment of individuals with type II diabetes mellitus. However, according to the International Pancreas Transplant Registry data the proportion of pancreas transplant recipients worldwide who have type II diabetes has increased over time.
Pancreas transplantation has been proposed to achieve insulin independence in persons with type II diabetes mellitus. Although the evidence in the peer reviewed medical literature is limited pancreas transplantation is an alternative treatment for insulin dependent individuals with type II diabetes mellitus.
For individuals who have insulin dependent diabetes and severe complications who receive pancreas transplant alone (PTA), the evidence includes registry studies. Data from international and national registries have found that graft and patient survival rates after pancreas transplant alone have improved over time (e.g. 3 year survival rate of 95%). The evidence is sufficient to determine that pancreas transplant alone (PTA) results in meaningful improvements in net health outcomes.
Pancreas transplant after kidney (PAK) transplantation permits uremic patients to benefit from a living-related kidney graft, if available, and to benefit from a subsequent pancreas transplant that is likely to improve quality of life compared with 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.
The purpose of a pancreas transplant after kidney (PAK) transplant in patients who have insulin-dependent diabetes is to provide a treatment option that is an alternative to or an improvement on existing therapies.
Bazarbachi et. al. (2013) reviewed a single center’s experience with pancreas after kidney (PAK) transplant and simultaneous-kidney pancreas (SPK) transplant. Between 2002 and 2010, 172 pancreas transplant were performed in diabetic patients (123 SPK, 49 PAK). The median length of time between kidney transplant and pancreas transplant in the PAK group was 4.8 years. Graft and patient survival rates were similar for both groups. Death-censored pancreas graft survival rates for SPK and PAK were 94% and 90% at 1 year, 92% and 90% at 3 years, and 85% and 85% at 5 years (p=0.93), all respectively. Patient survival rates (calculated from the time of pancreas transplantation) in the SPK and PAK groups were respectively 98% and 100% after 1 year, 96% and 100% after 3 eyars, and 94% to 100% after 5 years (p=0.09).
For individuals who have insulin dependent diabetes who receive a pancreas transplant after a kidney (PAK) transplant, the evidence includes case series and registry studies. Data from national and international registries have found relatively high patient survival rates after pancreas transplant after kidney (PAK), a 3 year survival rate of 93%. A 2013 analysis of data from a single center found similar patient survival and death-censored pancreas graft survival rates after PAK and SPK transplants. The evidence is sufficient to determine the technology results in a meaningful improvement in the net health outcome.
The kidney is frequently transplanted with the pancreas. Many people suffering from pancreas failure also have renal failure. In most cases a kidney-pancreas transplant is performed from a cadaveric donor. The purpose of simultaneous pancreas-kidney (SPK) transplant in patients who have insulin dependent diabetes with uremia is to provide a treatment option that is an alternative to or an improvement on existing therapies.
Analysis of a U.K. registry data by Barlow et. al. (2017) compared outcomes in patients with type I diabetes and end stage renal disease who had simultaneous pancreas-kidney (SPK) transplants (n=1739) with live donor transplants (n=370). In multivariate analysis, there was no significant association between type of transplant and patient survival (hazard ratio 0.71;95% CI, 0.47 to 1.06; p=0.095). Simultaneous pancreas-kidney recipients with a functioning pancreas graft and significantly better overall survival than those with a living donor kidney transplant (p<0.001).
Simultaneous pancreas-kidney (SPK) transplants have been found to reduce mortality in patients with type I diabetes. Van Dellen et. al. (2013) reported on a retrospective analysis of data for 148 SPK patients and a wait-list control group of 120 patients. All patients had type I insulin dependent diabetes. The study also included 33 patients who had pancreas after kidney (PAK) transplant and 11 patients who had pancreas transplant alone (PTA). Overall mortality (mortality at any time point) was 30% (30/120) for the waiting list and 9% (20/193) for transplanted patients; the difference between groups was statistically significant (p<0.001). The 1 year mortality rate was 13% (n=16) for the waiting list and 4% (n=8) for the transplant group (p<0.001).
There is some data on outcomes in patients with type II compared with type I diabetes. In 2011, Sampaio et. al. published an analysis of date from the United Network for Organ Sharing (UNOS) database. The investigators compared outcomes in 6141 patients with type I diabetes and 582 patients with type II diabetes who underwent SPK between 2000 and 2007. In adjusted analyses, outcomes were similar between the two groups. After adjusting for other factors such as body weight, dialysis time, and cardiovascular comorbidities, type II diabetes was not associated with an increased risk of pancreas or kidney graft failure or mortality compared with type I diabetes.
For individuals who have insulin-dependent diabetes with uremia who receive simultaneous pancreas-kidney (SPK) transplant, the evidence includes registry studies. Data from national and international registries have found relatively high patient survival rates with simultaneous pancreas-kidney (SPK) transplants, a 3 year survival rate of 95%. A retrospective analysis found a higher survival rate in patients with type I diabetes who had an SPK transplant than in those on a waiting list. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcomes.
The last four decades have seen a significant and progressive improvement in outcomes for pancreas transplantation. Improvements in immunosuppression, surgical technique and post-transplant management have all contributed to better graft survival. However, despite refinements in surgical technique, technical failure is defined by the International Pancreas Transplant Registry as graft loss secondary to vascular thrombosis, bleeding, anastomotic leaks or infection/pancreatitis and is responsible for more than 50% of all pancreas grafts lost in the first 6 months following transplantation. Thrombosis accounts for more than one-half of these technical failures, and may be influenced by donor and recipient factors, preservation and ischemic injury, immunological issues and surgical technique.
The decision to retransplant the pancreas after an early graft failure is complex. Prior to proceeding with retransplantation, a careful analysis of the factors contributing to the technical failure must be undertaken and reversible risk factors must be addressed. Surgical issues leading to thrombosis such as improper suturing of the vascular anastomosis, poor positioning of the allograft or inadequate hemostasis may be the primary cause of graft thrombosis. However, there may be no obvious surgical cause for graft loss identified. Reconfirming the tissue typing with the original donor and evaluating the patient for hypercoagulable state should be considered prior to attempting retransplantation in order to guide anticoagulation and immunosuppression management for the second graft.
Following appropriate evaluation for the causes of graft failure, repeat pancreas transplantation may be considered, although the optimal timing for retransplantation remains somewhat controversial. From a surgical perspective, retransplanting in the early post-pancreatectomy period may be preferable because extensive adhesions have not yet formed, this facilitates placing the new graft in the same anatomic site as the prior transplant. Some previous studies suggest that immediate retransplantation is associated with similar graft and patient survival as primary transplants, others indicate that this approach is associated with higher incidence of post-operative complications and rejection leading to premature loss of the second graft.
Several centers have published outcomes after pancreas retransplantation and generally reported comparable graft and patient survival rates after initial transplants and retransplants. For example, Fridell et. al. (2015) reported on 441 initial transplants and 20 late transplants. One year graft survival rates were 92% after initial transplant and 90% after retransplant (p=0.48). Similarly, 1 year patient survival rates were 96% after initial transplant and 95% after retransplant (p=0.53). However, Rudolph et. al. (2015) who assessed the largest number of patients, reported higher graft survival rates but not patient survival rates, after primary transplant. A total of 2145 pancreas transplants were performed, 415 (19%) of which were retransplants. The death-censored graft survival rate at 1 year was 88.2% in initial transplants and 75% in retransplants (p<0.001). Patient survival rates at 1 year were 91% after initial transplant and 88% after retransplant (p=0.06).
For individuals who have had a prior pancreas transplant who still meet criteria for a pancreas transplant who receive pancreas retransplantation, the evidence includes national and international data reported form specific transplant centers that have generally reported similar graft and patient survival rates after pancreas retransplantation compared with initial tarnsplantation. Although there are no standard guidelines regarding multiple pancreas transplants, each transplant center has its own guidelines based on experience. The evidence is sufficient to determine that pancreas retransplantation in patients who still meet criteria for transplant results in meaningful improvement in net health outcomes.
In 2014, the American Diabetes Association issued a position statement regarding type I diabetes through the life span, which included recommendations regarding pancreas transplants.
Successful pancreas transplantation has been demonstrated to be efficacious in significantly improving the quality of life of people with diabetes, primarily by eliminating the need for exogenous insulin, frequent daily blood glucose measurements, and many of the dietary restrictions improved by the disorder. Transplantation can also eliminate the acute complications of diabetes.
Recommendations
In 2018 the following is the allocation policies of the Organ Procurement and Transplantation Network for the Allocation of Pancreas and Kidney-Pancreas:
Each candidate registered on the pancreas waiting list must meet one of the following requirements:
Each candidate registered on the kidney-pancreas waiting list must be diagnosed with diabetes or have pancreatic exocrine insufficiency with renal insufficiency.
Prior approval is required.
See related medical policy 07.03.01 Pancreatic Islet Cell Transplant
Pancreas transplant alone (PTA) may be considered medically necessary in patients who have insulin-dependent diabetes mellitus with severe disabling and life threatening hypoblycemic unawareness due to labile diabetes despite optimal medical management (also, see policy guidelines below).
Pancreas transplant after a prior kidney (PAK) transplant may be considered medically necessary in patients with insulin-dependent diabetes.
Simultaneous pancreas-kidney (SPK) transplant may be considered medically necessary in insulin-dependent diabetics with impending or established renal failure.
Pancreas transplant alone (PTA), pancreas transplant after prior kidney transplant (PAK), or simultaneous pancreas-kidney transplant (SPK) performed for any other conditions not listed above will be considered not medically necessary.
Pancreas transplant alone (PTA), pancreas after kidney (PAK) or simultaneous pancreas-kidney (SPK) retransplantation after a failure of the primary graft may be considered medically necessary provided the individual meets the transplant criteria above.
Candidates for pancreas transplant alone (PTA) should additionally meet 1 of the following severity of illness criteria:
In addition, most pancreas transplant patients will have type I diabetes mellitus. Those transplant candidates with type II diabetes mellitus, in addition to being insulin dependent, should also not be obese (body mass index (BMI) should be 32 kg/m2 or less).
Although there are no standard guidelines regarding multiple pancreas transplants (retransplantations), the following information may aid in case review:
Wellmark medical policies address the complex issue of technology assessment of new and emerging treatments, devices, drugs, etc. They are developed to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. Wellmark medical policies contain only a partial, general description of plan or program benefits and do not constitute a contract. Wellmark does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Wellmark or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. Our medical policies may be updated and therefore are subject to change without notice.
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