Medical Policy
Policy Num: 07.003.005
Policy Name: Allogeneic Pancreas Transplant
Policy ID: [07.003.005] [Ac / B / M+ / P+] [7.03.02]
Last Review: September 08, 2023
Next Review: September 20, 2024
Related Policies:
01.001.024 - Artificial Pancreas Device Systems
07.003.014 - Kidney Transplant
07.003.011 - Islet Transplantation
Allogeneic Pancreas Transplant
Population Reference No. |
Populations |
Interventions |
Comparators |
Outcomes |
1 |
Individuals: · With insulin-dependent diabetes |
Interventions of interest are: · Pancreas transplant after a kidney transplant |
Comparators of interest are: · Insulin therapy |
Relevant outcomes include: · Overall survival · Change in disease status · Treatment-related mortality · Treatment-related morbidity |
2 |
Individuals: · With insulin-dependent diabetes with uremia |
Interventions of interest are: · Simultaneous pancreas and kidney transplants |
Comparators of interest are: · Insulin therapy |
Relevant outcomes include: · Overall survival · Change in disease status · Treatment-related mortality · Treatment-related morbidity |
3 |
Individuals: · With insulin-dependent diabetes and severe complications |
Interventions of interest are: · Pancreas transplant alone |
Comparators of interest are: · Insulin therapy |
Relevant outcomes include: · Overall survival · Change in disease status · Treatment-related mortality · Treatment-related morbidity |
4 |
Individuals: · With a prior pancreas transplant who still meet criteria for a pancreas transplant |
Interventions of interest are: · Pancreas retransplant |
Comparators of interest are: · Insulin therapy |
Relevant outcomes include: · Overall survival · Change in disease status · Treatment-related mortality · Treatment-related morbidity |
Transplantation of a healthy pancreas is a treatment for patients with insulin-dependent diabetes. Pancreas transplantation can restore glucose control and prevent, halt, or reverse the secondary complications from diabetes.
For individuals who have insulin-dependent diabetes who receive a pancreas transplant after a kidney transplant, the evidence includes retrospective studies and registry studies. Relevant outcomes are overall survival (OS), change in disease status, and treatment-related mortality and morbidity. Data from national and international registries have found relatively high patient survival rates with a pancreas transplant after a kidney transplant (eg, a 3-year survival rate of 94.5%). Single-center retrospective studies have found similar patient survival and death-censored pancreas graft survival rates with a pancreas transplant after a kidney transplant or a simultaneous pancreas and kidney (SPK) transplant. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.
For individuals who have insulin-dependent diabetes with uremia who receive SPK transplants, the evidence includes retrospective studies and registry studies. Relevant outcomes are OS, change in disease status, and treatment-related mortality and morbidity. Data from national and international registries have found relatively high patient survival rates after SPK transplant. A retrospective analysis found a higher survival rate in patients with type 1 diabetes who had an SPK transplant versus those on a waiting list. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.
For individuals who have insulin-dependent diabetes and severe complications who receive a pancreas transplant alone, the evidence includes registry studies. Relevant outcomes are OS, change in disease status, and treatment-related mortality and morbidity. Data from international and national registries have found that graft and patient survival rates after pancreas transplant alone have improved over time (eg, 3-year survival of 94.9%). The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.
For individuals who have had a prior pancreas transplant who still meet criteria for a pancreas transplant who receive pancreas retransplantation, the evidence includes retrospective studies and registry studies. Relevant outcomes are OS, change in disease status, and treatment-related mortality and morbidity. National data and specific transplant center data have generally found similar graft and patient survival rates after pancreas retransplantation compared with initial transplantation. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.
Not applicable.
The objective of this evidence review is to determine whether pancreas transplantation or retransplantation improves the net health outcome in patients with insulin-dependent diabetes compared with standard management without transplantation.
Pancreas transplant after a prior kidney transplant may be considered medically necessary in patients with insulin-dependent diabetes.
A combined pancreas and kidney transplant may be considered medically necessary in insulin-dependent diabetic patients with uremia.
Pancreas transplant alone may be considered medically necessary in patients with severely disabling and potentially life-threatening complications due to hypoglycemia unawareness and labile insulin-dependent diabetes that persists despite optimal medical management.
Pancreas retransplant after a failed primary pancreas transplant may be considered medically necessary in patients who meet criteria for pancreas transplantation.
Pancreas transplant is considered investigational in all other situations.
Potential contraindications for solid organ transplant that are subject to the judgment of the transplant center include the following:
Known current malignancy, including metastatic cancer
Recent malignancy with high risk of recurrence
Untreated systemic infection making immunosuppression unsafe, including chronic infection
Other irreversible end-stage diseases not attributed to kidney disease
History of cancer with a moderate risk of recurrence
Systemic disease that could be exacerbated by immunosuppression
Psychosocial conditions or chemical dependency affecting the ability to adhere to therapy.
Candidates for pancreas transplant alone should also meet one of the following severity of illness criteria:
Documented severe hypoglycemia unawareness as evidenced by chart notes or emergency department visits or
Documented potentially life-threatening labile diabetes, as evidenced by chart notes or hospitalization for diabetic ketoacidosis.
Additionally, most pancreas transplant individuals will have type 1 diabetes. Those transplant candidates with type 2 diabetes, in addition to being insulin-dependent, should also not be obese (body mass index should be ≤32 kg/m2). In 2018, individuals with type 2 diabetes accounted for 14.8% of all pancreas transplants, according to data from the Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients.1,
Although there are no standard guidelines for multiple pancreas transplants, the following information may aid in case review:
If there is early graft loss resulting from technical factors (eg, venous thrombosis), a retransplant may generally be performed without substantial additional risk.
Long-term graft losses may result from chronic rejection, which is associated with increased risk of infection following long-term immunosuppression, and sensitization, which increases the difficulty of finding a negative cross-match. Some transplant centers may wait to allow reconstitution of the immune system before initiating retransplant with an augmented immunosuppression protocol.
See the Codes table for details.
Transplants, such as a pancreas transplant, should be considered for coverage under the transplant benefit and should be evaluated for a charge in accordance with traditional transplant benefits.
Which expenses are incurred during the evaluation and procurement of organs and tissues should be compared with the scope of human organ transplant benefits for coverage determination. Typically, the following are considered human organ transplant benefits:
hospitalization of the recipient for medically recognized transplants from a donor to a transplant recipient;
evaluation tests requiring hospitalization to determine the suitability of both potential and actual donors, when such tests cannot be safely and effectively performed on an outpatient basis;
hospital room, board, and general nursing in semiprivate rooms;
special care units, such as coronary and intensive care;
hospital ancillary services;
physicians' services for surgery, technical assistance, administration of anesthetics, and medical care;
acquisition, preparation, transportation, and storage of organ;
diagnostic services;
drugs that require a prescription by federal law.
Other examples of benefits include specific charges or participation with registries for organ procurement, operating rooms, supplies, use of hospital equipment, and transportation of the tissue or organ to be evaluated.
Administration of products with a specific transplant benefit needs to be defined as to:
when the benefit begins (at the time of admission for the transplant or once the patient is determined eligible for a transplant, which may include tests or office visits before transplant);
when the benefit ends (at the time of discharge from the hospital or at the end of the required follow-up, including the immunosuppressive drugs administered on an outpatient basis).
Coverage usually is not provided for:
human organ transplant services, for which the cost is covered or funded by governmental, foundational, or charitable grants;
organs sold rather than donated to the recipient;
an artificial organ.
Benefits are determined by the group contract, member benefit booklet, and/or individual subscriber certificate in effect at the time services were rendered. Benefit products or negotiated coverages may have all or some of the services discussed in this medical policy excluded from their coverage.
Solid organ transplantation offers a treatment option for patients with different types of end-stage organ failure that can be lifesaving or provide significant improvements to a patient’s quality of life.2, Many advances have been made in the last several decades to reduce perioperative complications. Available data supports improvement in long-term survival as well as improved quality of life particularly for liver, kidney, pancreas, heart, and lung transplants. Allograft rejection remains a key early and late complication risk for any organ transplantation. Transplant recipients require life-long immunosuppression to prevent rejection. Patients are prioritized for transplant by mortality risk and severity of illness criteria developed by the Organ Procurement and Transplantation Network and United Network of Organ Sharing.
In 2022 , 42,889 transplants were performed in the United States procured from more than 36,400 deceased donors and 6400 living donors.3, Pancreas-kidney transplants were the fifth most common procedure, with 810 transplants performed in 2022. Pancreas-alone transplants were the sixth most common procedure, with 108 transplants performed in 2022.
Pancreas transplantation occurs in several different scenarios such as (1) a diabetic patient with renal failure who may receive a simultaneous cadaveric pancreas plus kidney transplant; (2) a diabetic patient who may receive a cadaveric or living-related pancreas transplant after a kidney transplantation (pancreas after kidney); or (3) a nonuremic diabetic patient with specific severely disabling and potentially life-threatening diabetic problems who may receive a pancreas transplant alone.
Data from the United Network for Organ Sharing and the International Pancreas Transplant Registry indicate that the proportion of simultaneous pancreas plus kidney transplant recipients worldwide who have type 2 diabetes has increased over time, from 6% of transplants between 2005 and 2009 to 9% of transplants between 2010 and 2014.4, Between 2010 and 2014, approximately 4% of pancreas after kidney transplants and 4% of pancreas alone transplants were performed in patients with type 2 diabetes. In 2019, patients with type 2 diabetes accounted for 20.6% of all pancreas transplants, according to data from the Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients.5, Patients with type 2 diabetes accounted for 6.2%, 1%, and 22.4% of pancreas alone, pancreas after kidney, and simultaneous pancreas plus kidney transplants, respectively.
Solid organ transplants are a surgical procedure and, as such, are not subject to regulation by the U.S. Food and Drug Administration (FDA).
The FDA regulates human cells and tissues intended for implantation, transplantation, or infusion through the Center for Biologics Evaluation and Research, under Code of Federal Regulation Title 21, parts 1270 and 1271. Solid organs used for transplantation are subject to these regulations.
This evidence review was created in December 1996 and has been updated regularly with searches of the PubMed database. The most recent literature update was performed through June 30, 2023.
This evidence review was informed in part by a TEC Assessment (1998), which focused on pancreas graft survival and health outcomes associated with both pancreas transplant alone (PTA) and pancreas after kidney (PAK) transplants.6, A TEC Assessment (2001) focused on pancreas retransplant also informed this evidence review.7,These assessments and subsequent evidence offer the following observations and conclusions.
Evidence reviews assess the clinical evidence to determine whether the use of a technology improves the net health outcome. Broadly defined, health outcomes are the length of life, quality of life, and ability to function-including benefits and harms. Every clinical condition has specific outcomes that are important to patients and managing the course of that condition. Validated outcome measures are necessary to ascertain whether a condition improves or worsens; and whether the magnitude of that change is clinically significant. The net health outcome is a balance of benefits and harms.
To assess whether the evidence is sufficient to draw conclusions about the net health outcome of a technology, 2 domains are examined: the relevance, and quality and credibility. To be relevant, studies must represent 1 or more intended clinical use of the technology in the intended population and compare an effective and appropriate alternative at a comparable intensity. For some conditions, the alternative will be supportive care or surveillance. The quality and credibility of the evidence depend on study design and conduct, minimizing bias and confounding that can generate incorrect findings. The randomized controlled trial (RCT) is preferred to assess efficacy; however, in some circumstances, nonrandomized studies may be adequate. Randomized controlled trials are rarely large enough or long enough to capture less common adverse events and long-term effects. Other types of studies can be used for these purposes and to assess generalizability to broader clinical populations and settings of clinical practice.
Promotion of greater diversity and inclusion in clinical research of historically marginalized groups (e.g., People of Color [African-American, Asian, Black, Latino and Native American]; LGBTQIA (Lesbian, Gay, Bisexual, Transgender, Queer, Intersex, Asexual); Women; and People with Disabilities [Physical and Invisible]) allows policy populations to be more reflective of and findings more applicable to our diverse members. While we also strive to use inclusive language related to these groups in our policies, use of gender-specific nouns (e.g., women, men, sisters, etc.) will continue when reflective of language used in publications describing study populations.
Much of the published literature consists of retrospective data reported by single centers and registry data. The extant RCTs compare immunosuppression regimens and surgical techniques and therefore do not compare pancreas transplantation with insulin therapy, or simultaneous pancreas and kidney (SPK) transplant with insulin therapy and hemodialysis.
The purpose of a pancreas after kidney (PAK) transplant in individuals who have insulin-dependent diabetes is to provide a treatment option that is an alternative to or an improvement on existing therapies.
The following PICO was used to select literature to inform this review.
The relevant population of interest is individuals with insulin-dependent diabetes.
The therapy being considered is a PAK transplant.
Pancreas after kidney transplantation permits patients with insulin-dependent diabetes 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. Patients with insulin-dependent diabetes for whom a cadaveric kidney graft is available, but a pancreas graft is not simultaneously available, benefit similarly from a later pancreas transplant.
The following therapy is currently being used to make decisions about insulin-dependent diabetes: insulin therapy.
The general outcomes of interest are overall survival (OS), disease progression, graft failure, and adverse events. In the short-term (post-surgery), follow-up monitors for graft failure. Long-term follow-up has extended to 10 years as survival improves.
Methodologically credible studies were selected using the following principles:
To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs;
In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.
To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.
Within each category of study design, studies with larger sample sizes and longer duration were preferred.
Studies with duplicative or overlapping populations were excluded.
As reported by Gruessner and Gruessner (2016), according to United Network for Organ Sharing (UNOS) and International Pancreas Transplant Registry data, patient survival rates after PAK conducted from 2010 to 2014 were 97.9% after 1 year and 94.5% after 3 years.4, This compares with 1-year (96.4%) and 3-year (93.1%) patient survival rates for transplants conducted from 2005 to 2009.
Parajuli et al (2019) described a single center's experience with 635 pancreas and kidney transplant patients (611 SPK, 24 PAK).8, Transplants were performed between 2000 and 2016. The mean length of time between kidney transplant and pancreas transplant was 23.8 months in the PAK group. Pancreas rejection rates at 1 year post-transplant were 4% and 9% with PAK and SPK respectively (p=.39). During the entire study period, PAK patients were more likely to experience pancreas rejection (38% vs. 16%; p=.005). Kidney and pancreas graft survival rates did not differ between groups at 1 year or at last follow-up. Pancreas graft survival rates for PAK and SPK at 1 year were 100% and 89%, respectively (p=.09). Death-censored pancreas graft failure rates for PAK and SPK at last follow-up were 13% and 25%, respectively (p=.17). Patient survival at last follow-up was similar between groups (71% with PAK vs. 68% with SPK; p=.79).
Bazarbachi et al (2013) reviewed a single center's experience with PAK and SPK.9, Between 2002 and 2010, 172 pancreas transplants 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=.93), all respectively. Patient survival rates (calculated from the time of pancreas transplantation) in the SPK and PAK groups were 98% and 100% after 1 year, 96% and 100% after 3 years, and 94% and 100% after 5 years (p=.09), respectively.
Fridell et al (2009) reported on a retrospective review of a single center's experience with PAK and SPK since 2003, when current induction or tacrolimus immunosuppressive strategies became standard.10, Of the 203 cases studied, 61 (30%) were PAK and 142 (70%) were SPK. One-year patient survival rates were 98% PAK and 95% SPK (p=.44). Pancreas graft survival rates at 1 year were 95% and 90%, respectively (p=.28). The authors concluded that in the modern immunosuppressive era, PAK should be considered as an acceptable alternative to SPK in candidates with an available living kidney donor.
Kleinclauss et al (2009) retrospectively reviewed data from 307 diabetic kidney transplant recipients from a single center and compared renal graft survival rates in those who subsequently received a pancreatic transplant with those who did not.11, The comparative group was analyzed separately based on whether patients were medically eligible for pancreas transplant, but chose not to proceed for financial or personal reasons, or were ineligible for medical reasons. The ineligible (n=57) group differed significantly at baseline from both the PAK group (n=175) and the eligible group (n=75) with respect to age, type of diabetes, and dialysis experience; kidney graft survival rates at 1, 5, and 10 years were lower in the ineligible group (75%, 54%, and 22%, respectively; p<.001) than in the other groups (for the PAK group, 98%, 82%, and 67% vs. for the eligible group, 100%, 84%, and 62%). The authors concluded that the subsequent transplant of a pancreas after a living donor kidney transplant does not adversely affect patient or kidney graft survival rates.
Data from national and international registries have found relatively high patient survival rates after PAK (eg, a 3-year survival rate of 94.5%). Single-center retrospective analyses have found similar patient survival and death-censored pancreas graft survival rates after PAK and SPK transplants.
For individuals who have insulin-dependent diabetes who receive a pancreas transplant after a kidney transplant, the evidence includes retrospective studies and registry studies. Relevant outcomes are overall survival (OS) , change in disease status, and treatment-related mortality and morbidity. Data from national and international registries have found relatively high patient survival rates with a pancreas transplant after a kidney transplant (eg, a 3-year survival rate of 94.5%). Single-center retrospective studies have found similar patient survival and death-censored pancreas graft survival rates with a pancreas transplant after a kidney transplant or a simultaneous pancreas and kidney (SPK) transplant. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.
Population Reference No. 1 Policy Statement |
[X] Medically Necessary | [ ] Investigational |
The purpose of a SPK transplant in individuals who have insulin-dependent diabetes with uremia is to provide a treatment option that is an alternative to or an improvement on existing therapies.
The following PICO was used to select literature to inform this review.
The relevant population of interest is individuals who have insulin-dependent diabetes with uremia.
The therapy being considered is an SPK transplant.
The following therapy is currently being used to make decisions about insulin-dependent diabetes with uremia: insulin therapy.
The general outcomes of interest are OS, disease progression, graft failure, and adverse events. In the short-term (post-surgery), follow-up monitors for graft failure. Long-term follow-up has extended to 10 years as survival improves.
Methodologically credible studies were selected using the following principles:
To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs;
In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.
To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.
Within each category of study design, studies with larger sample sizes and longer duration were preferred.
Studies with duplicative or overlapping populations were excluded.
The U.S.-based Organ Procurement and Transplant Network (OPTN) has reported a 1-year patient survival rate of 97.5% (95% confidence interval [CI], 96.9% to 98.0%) for primary SPK procedures performed between 2008 and 2015.12, Three- and 5-year patient survival rates were 94.8% (95% CI, 93.9% to 95.5%) and 88.9% (95% CI, 87.8% to 89.9% ), respectively.
An analysis of U.K. registry data by Barlow et al (2017) compared outcomes in patients with type 1 diabetes and end-stage renal disease who had SPK transplants (n=1739) versus live donor kidney transplants (n=370).13, 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=.095). Simulaneous pancreas plus kidney recipients with a functioning pancreas graft had significantly better OS than those with a living donor kidney transplant (p<.001).
Simultaneous pancreas plus kidney transplants have been found to reduce mortality in patients with type 1 diabetes. Van Dellen et al (2013) in the U.K. reported on a retrospective analysis of data for 148 SPK patients and a wait-list control group of 120 patients.14, All patients had type 1 (insulin-dependent) diabetes. (The study also included 33 patients who had PAK and 11 patients who had 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<.001). The 1-year mortality rate was 13% (n=16) for the waiting list and 4% (n=8) for the transplant group (p<.001).
Sampaio et al (2011) published an analysis of data from the UNOS database.15, Outcomes for 6141 patients with type 1 diabetes and 582 patients with type 2 diabetes who underwent SPK were similar for both groups in adjusted analyses. After adjusting for other factors (eg, body weight; dialysis time; cardiovascular comorbidities), type 2 diabetes was not associated with an increased risk of pancreas or kidney graft failure or mortality compared with type 1 diabetes.
Data from national and international registries have found relatively high patient survival rates after SPK transplants (eg, a 3-year survival rate of 94.8% and a 5-year survival rate of 88.9% ). A retrospective analysis found a higher survival rate in patients with type 1 diabetes who had an SPK transplant than in those on a waiting list.
For individuals who have insulin-dependent diabetes with uremia who receive SPK transplants, the evidence includes retrospective studies and registry studies. Relevant outcomes are OS, change in disease status, and treatment-related mortality and morbidity. Data from national and international registries have found relatively high patient survival rates after SPK transplant. A retrospective analysis found a higher survival rate in patients with type 1 diabetes who had an SPK transplant versus those on a waiting list. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.
Population Reference No. 2 Policy Statement |
[X] Medically Necessary | [ ] Investigational |
The purpose of a pancreas transplant in individuals who have insulin-dependent diabetes with severe diabetic complications is to provide a treatment option that is an alternative to or an improvement on existing therapies.
The following PICO was used to select literature to inform this review.
The relevant population of interest is individuals who have insulin-dependent diabetes with severe diabetic complications.
Although pancreas transplantation is generally not considered a life-saving treatment for individuals with insulin-dependent diabetes, in a small subset of patients who experience life-threatening complications from diabetes, pancreas transplantation could be considered life-saving. Pancreas transplant alone has also been investigated in patients following total pancreatectomy for chronic pancreatitis. In addition to the immune rejection issues common to all allograft transplants, autoimmune destruction of beta cells has been observed in the transplanted pancreas, presumably from the same mechanism responsible for type 1 diabetes. 16,
Most patients undergoing PTA are those with either hypoglycemic unawareness or labile diabetes. However, other exceptional circumstances may exist where patients with nonuremic type 1 diabetes have significant morbidity risks due to secondary complications of diabetes (eg, peripheral neuropathy) 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 exceptional diabetic patients, it 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 therapy being considered is PTA.
The following therapy is currently being used to make decisions about insulin-dependent diabetes with severe diabetic complications: insulin therapy.
The general outcomes of interest are OS, disease progression (eg, end-stage renal disease), graft failure, and adverse events (eg, hypoglycemia, labile diabetes). In the short-term (post-surgery), follow-up monitors for graft failure. Long-term follow-up has extended to 5 years as survival improves.
Methodologically credible studies were selected using the following principles:
To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs;
In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.
To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.
Within each category of study design, studies with larger sample sizes and longer duration were preferred.
Studies with duplicative or overlapping populations were excluded.
Pancreas transplant graft survival has improved over time. According to International Pancreas Transplant Registry data, 1-year graft function increased from 51.5% for 1987 to 1993 to 77.8% for 2006 to 2010 (p<.001).17, One-year immunologic graft loss remained higher (6.0%) after PTA than after PAK (3.7%) or SPK (1.8%). According to UNOS and the International Pancreas Transplant Registry data, for the period from 2010 to 2014, the patient survival rate for PTA was 96.3% after 1 year and 94.9% after 3 years.4, This compares with 1-year and 3-year patient survival rates of 97.5% and 93.3% for 2005 to 2009, respectively. According to Gruessner (2011), in carefully selected patients with type 1 diabetes and severely disabling and potentially life-threatening complications due to hypoglycemia unawareness and persistent labile diabetes despite optimal medical management, the benefits of PTA were judged to outweigh the risk of performing pancreas transplantation with subsequent immunosuppression.17,
Boggi et al (2021) reported results of a single-center cohort study of 66 patients with type 1 diabetes who received PTA.18, After 10 years of follow-up, patient survival was 92.4%. Of these patients surviving to 10 years, 57.4% had optimal graft function (defined as normoglycemia and insulin independence) and 3.2% had good graft function (defined as HbA1c <7%, no severe hypoglycemia, >50% reduction in insulin requirements, and restoration of clinically significant C-peptide production). Four patients (6.0%) developed end-stage renal failure (stage 5, estimated glomerular filtration rate [eGFR] < 15 ml/min/1.73 m2), and 2 additional patients (3.0%) showed stage 4 kidney failure (eGFR 15 to 30 ml/min/1.73 m2) at the 10-year posttransplant assessment.
Noting that nephrotoxic immunosuppression may exacerbate diabetic renal injury after PTA, Scalea et al (2008) reported on a single institutional review of 123 patients who received 131 PTA for the development of renal failure.19, Mean graft survival was 3.3 years (range, 0 to 11.3 years), and 21 patients were lost to follow-up. At a mean follow-up of 3.7 years, the mean eGFR was 88.9 mL/min/1.73 m2 pretransplantation and 55.6 mL/min/1.73 m2 posttransplantation. All but 16 patients had a decrease in eGFR. Thirteen developed end-stage renal disease, which required kidney transplantation at a mean of 4.4 years. The authors suggested that patients should be made aware of the risk and only the most appropriate patients should be offered PTA.
Data from international and national registries have found that graft and patient survival rates after PTA have improved over time. For the period of 2010 to 2014, 1- and 3-year survival rates had improved to 96.3% and 94.9%, respectively.
For individuals who have insulin-dependent diabetes and severe complications who receive pancreas transplant alone, the evidence includes registry studies. Relevant outcomes are OS, change in disease status, and treatment-related mortality and morbidity. Data from international and national registries have found that graft and patient survival rates after pancreas transplant alone have improved over time (eg, 3-year survival of 94.9%). The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.
Population Reference No. 3 Policy Statement |
[X] Medically Necessary | [ ] Investigational |
The purpose of a pancreas retransplant in individuals who have had a prior pancreas transplant and still meet criteria for a pancreas transplant is to provide a treatment option that is an alternative to or an improvement on existing therapies.
The following PICO was used to select literature to inform this review.
The relevant population of interest is individuals who have had a prior pancreas transplant and still meet criteria for a pancreas transplant.
The therapy being considered is a pancreas retransplant.
The approach to retransplantation varies by cause of failure. Surgical and technical complications such as venous thrombosis are the leading cause of pancreatic graft loss among diabetic patients. Graft loss from chronic rejection may result in sensitization, increasing both the difficulty of finding a cross-matched donor and the risk of rejection of a subsequent transplant. Each transplant center has guidelines based on experience; some centers may wait to allow reconstitution of the immune system before initiating retransplant with an augmented immunosuppression protocol.
The following therapy is currently being used to make decisions about a failed pancreas transplant: insulin therapy.
The general outcomes of interest are OS, graft progression, transplant failure, and adverse events. In the short-term (post-surgery), follow-up monitors for graft failure. Long-term follow-up has extended over time to 5 years as survival improves.
Methodologically credible studies were selected using the following principles:
To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs;
In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.
To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.
Within each category of study design, studies with larger sample sizes and longer duration were preferred.
Studies with duplicative or overlapping populations were excluded.
Parajuli et al (2019) compared outcomes among SPK patients who did or did not receive pancreas retransplantation after isolated pancreas graft failure.20, Among 109 SPK patients with pancreas graft failure, 25 underwent pancreas retransplantation and 84 did not. The mean follow-up time after pancreas graft failure was longer among patients who underwent pancreas retransplantation (7.6 years vs. 4.6 years). Rates of death-censored kidney graft failure at last follow-up were lower among patients who underwent pancreas retransplantation (24% vs. 48%; p=.04). However, given the retrospective nature of the study, selection bias may have influenced the observed outcomes. Patient survival was not significantly different between groups. Among patients who underwent retransplantation, 1-year pancreas graft survival was 84%.
The retrospective observational study by Gasteiger at al (2018) assessed the outcomes of pancreas retransplantation for patients with pancreas graft failure (defined as a return to insulin dependence).21, The study evaluated pancreas retransplantations performed between 1997 and 2013 at a single Austrian medical university. Fifty-two pancreas retransplantations were identified, and the median follow-up was 65.0 (range, 0.8 to 174.3) months. At 5 years, the overall patient survival rate was 89%; the survival rate for patients who underwent SPK retransplantation was 90% (18/20), and the survival rate for those who received only a pancreas retransplantation was 88% (28/32). Graft survival rates were 79% at 1 year and 69% at 5 years. The 5-year graft survival rate was higher following SPK retransplantation than pancreas retransplantation alone: 80% for SPK (16/20) versus 63% (20/32) for pancreas alone (p=.226). During the entire follow-up, 42% (22/52) of the grafts were lost. Two factors significantly associated with long-term graft survival were early surgical complications (odds ratio, 3.29; 95% CI, 1.09 to 9.99; p=.035) and acute rejection (odds ratio, 4.49; 95% CI, 1.59 to 12.68; p=.005). The authors note that because pancreas transplantation is not a life-saving operation, the risks and benefits of the procedure must be carefully considered.
The OPTN has reported data on transplants performed between 2008 and 2015.12, Patient survival rates after repeat PTA were similar to survival rates after primary transplants. For example, the 1-year survival rate was 91.0% (95% CI, 88.7% to 92.8%) after a primary pancreas transplant and 96.4% (95% CI, 92.1% to 98.4% ) after a repeat pancreas transplant. The numbers of patients transplanted were not reported, but OPTN data stated that 668 patients were alive 1 year after primary transplant and 157 after repeat transplants. The 3-year patient survival rate was 87.5% (95% CI, 85.1% to 89.6% ) after primary transplants and 91.2% (95% CI, 86.2% to 94.4% ) after repeat transplants. The 5-year patient survival rate was 79.9% (95% CI, 77.4% to 82.2% ) after primary transplants and 83.7% (95% CI, 78.2% to 88.0% ) after repeat transplants. The 1-year graft survival rate was 81.8% (95% CI, 78.9% to 84.3%) after primary pancreas transplant and 77.7% (95% CI, 70.8% to 83.1%) after repeat transplant.
Data are similar for patients receiving SPK transplants, but follow-up data are only available on a small number of patients who had repeat SPK transplants, so estimates of survival rates in this group are imprecise. Three-year patient survival rate was 94.8% (95% CI, 93.9% to 95.5%) after primary SPK transplant and 87.9% (95% CI, 73.4% to 94.8% ) after a repeat SPK transplant. The number of patients living 3 years after transplant was 2871 after a primary combined procedure and 36 after a repeat combined procedure.
Several centers have published outcomes after pancreas retransplantation and generally reported comparable graft and patient survival rates after initial transplants and retransplants.22,23,24,25, The largest and most recent studies are further described here. Fridell et al (2015) reported on 441 initial transplants and 20 late transplants.23, One-year graft survival rates were 92% after initial transplant and 90% after retransplant (p=.48). Similarly, 1-year patient survival rates were 96% after initial transplants and 95% after retransplants (p=.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.25, A total of 2145 pancreas transplants were performed, 415 (19.3%) of which were retransplants. The death-censored graft survival rate at 1 year was 88.2% in initial transplants and 75.0% in retransplants (p<.001). Patient survival rates at 1 year were 91.3% after initial transplants and 88.2% after retransplants (p=.06).
National and international data reported from specific transplant centers have generally reported similar graft and patient survival rates after pancreas retransplantation compared with initial transplantation.
For individuals who have had a prior pancreas transplant who still meet criteria for a pancreas transplant who receive pancreas retransplantation, the evidence includes retrospective studies and registry studies. Relevant outcomes are OS, change in disease status, and treatment-related mortality and morbidity. National data and specific transplant center data have generally found similar graft and patient survival rates after pancreas retransplantation compared with initial transplantation. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.
Population Reference No. 4 Policy Statement |
[X] Medically Necessary | [ ] Investigational |
Current OPTN policy permits human immunodeficiency virus (HIV) -positive transplant candidates.26,
The American Society of Transplantation (2019) published a guideline on solid organ transplantation in HIV-infected patients.27, For kidney-pancreas transplants, the following criteria for transplantation are suggested:
Cluster of differentiation 4 count >200 cells/mL for at least 3 months (insufficient data to recommend for or against transplantation in patients with counts >100 cells/mL and no history of opportunistic infection)
Undetectable HIV viral load while receiving antiretroviral therapy
Documented compliance with a stable antiretroviral therapy regimen
Absence of active opportunistic infection and malignancy
Absence of chronic wasting or severe malnutrition
The guideline authors note that patients with a previous history of progressive multifocal leukoencephalopathy, chronic interstitial cryptosporidiosis, primary central nervous system lymphoma, or visceral Kaposi's sarcoma were excluded from studies of solid organ transplantation in HIV-infected patients. Patients with HIV and concomitant controlled hepatitis B infection may be considered for transplant. Caution is recommended in hepatitis C-coinfected patients who have not been initiated on direct acting antiviral therapy.
Recipient age older than 50 years has been considered a relative contraindication for a pancreas transplant. Several analyses of outcomes by patient age group have prompted general agreement among experts that age should not be a contraindication; however, age-related comorbidities must be considered when selecting patients for transplantation.
In the largest study of pancreas outcomes by recipient age, Siskind et al (2014) assessed data from the UNOS database.28, Investigators included all adults who received SPK or PTA transplants between 1996 and 2012 (N=20,854). This included 3160 patients between the ages of 50 and 59 years, and 280 patients aged 60 years or older. Overall, Kaplan-Meier survival analysis found statistically significant differences in patient survival (p<.001) and graft survival (p<.001) by age category. 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 immunologic graft rejection as a result of 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 patients age, they are more likely to die from other causes. Still, patient survival rates at 5 and 10 years are relatively high, as shown in Table 1.
Years After Transplant | Age 18 to 29, % | Age 30 to 39, % | Age 40 to 49, % | Age 50 to 59, % | Age 60+, % |
1 year | 95.4 | 96.0 | 94.9 | 93.3 | 91.0 |
5 years | 86.3 | 87.8 | 85.7 | 81.6 | 71.4 |
10 years | 73.5 | 76.8 | 71.8 | 61.5 | 42.5 |
Adapted from Siskind et al (2014).28,
Among previous studies on pancreas outcomes in older patients, Shah et al (2013) reviewed data on 405 patients who underwent PTA transplants between 2003 and 2011.29, One-year patient survival was 100% for patients younger than age 30 years, 98% for patients aged 30 to 39 years, 94% for patients aged 40 to 49 years, 95% for patients aged 50 to 59 years, and 93% for patients aged 60 years or older. There was no statistically significant difference in patient survival by age group (p=.38). Findings were similar for 1-year graft survival; there was no statistically significant difference in outcomes by age of transplant recipients (p=.10).
A study by Afaneh et al (2011) reviewed data on 17 individuals at least 50 years old and 119 individuals younger than 50 years who had a pancreas transplant at a single institution in the U.S.30, The 2 groups had similar rates of surgical complications, acute rejection, and nonsurgical infections. Overall patient survival was similar. Three- and 5-year survival rates were 93% and 90%, respectively, in the younger group, and 92% and 82%, respectively, in the older group. Schenker et al (2011) compared outcomes in 69 individuals at least 50 years old with 329 individuals younger than 50 years who had received pancreas transplants.31, Mean duration of follow-up was 7.7 years. One-, 5-, and 10-year patient and graft survival rates were similar for the groups. For example, the 5-year patient survival rate was 89% in both groups. The 5-year pancreas graft 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 et al (2011) article,32, agreed that individuals age 50 years and older are suitable candidates for pancreas transplantation.
Population Reference No. 4 Policy Statement |
[X] Medically Necessary | [ ] Investigational |
The purpose of the following information is to provide reference material. Inclusion does not imply endorsement or alignment with the evidence review conclusions.
Guidelines or position statements will be considered for inclusion in ‘Supplemental Information’ if they were issued by, or jointly by, a US professional society, an international society with US representation, or National Institute for Health and Care Excellence (NICE). Priority will be given to guidelines that are informed by a systematic review, include strength of evidence ratings, and include a description of management of conflict of interest.
The Organ Procurement and Transplantation Network updated its comprehensive list of transplant-related policies, most recently in June 2023.26,
For pancreas registration:
"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."
For combined kidney plus pancreas registration: "Each candidate registered on the kidney-pancreas waiting list must be diagnosed with diabetes or have pancreatic exocrine insufficiency with renal insufficiency."
Not applicable.
An allogeneic pancreas transplant is covered under Medicare when performed in a facility approved by Medicare as meeting institutional coverage criteria.33, The Centers for Medicare & Medicaid Services made the following national coverage decision on pancreas transplant for Medicare recipients.34,
"A. General
Pancreas transplantation is performed to induce an insulin-independent, euglycemic state in diabetic patients. The procedure is generally limited to those patients with severe secondary complications of diabetes, including kidney failure. However, pancreas transplantation is sometimes performed on patients with labile diabetes and hypoglycemic unawareness.
B. Nationally Covered Indications
Effective … 1999, whole organ pancreas transplantation is nationally covered by Medicare when performed simultaneously with or after a kidney transplant. If the pancreas transplant occurs after the kidney transplant, immunosuppressive therapy begins with the date of discharge from the inpatient stay for the pancreas transplant.
Effective … 2006, pancreas transplants alone (PA) are reasonable and necessary for Medicare beneficiaries in the following limited circumstances:
PA will be limited to those facilities that are Medicare-approved for kidney transplantation.
Patients must have a diagnosis of type I diabetes:
Patient with diabetes must be beta-cell autoantibody-positive; or
Patient must demonstrate insulinopenia defined as a fasting C-peptide level that is less than or equal to 110% of the lower limit of normal of the laboratory's measurement method. Fasting C-peptide levels will only be considered valid with a concurrently obtained fasting glucose ≤225 mg/dL;
Patients must have a history of medically uncontrollable labile (brittle) insulin-dependent diabetes mellitus with documented recurrent, severe, acutely life-threatening metabolic complications that require hospitalization. Aforementioned complications include frequent hypoglycemia unawareness or recurring severe ketoacidosis, or recurring severe hypoglycemic attacks;
Patients must have been optimally and intensively managed by an endocrinologist for at least 12 months with the most medically recognized advanced insulin formulations and delivery systems;
Patients must have the emotional and mental capacity to understand the significant risks associated with surgery and to effectively manage the lifelong need for immunosuppression; and,
Patients must otherwise be a suitable candidate for transplantation."
Nationally noncovered indications include "Transplantation of partial pancreatic tissue or islet cells (except in the context of a clinical trial)."
Some currently ongoing and unpublished trials that might influence this review are listed in Table 2.
NCT No. | Trial Name | Planned Enrollment | Completion Date |
Ongoing | |||
NCT01047865 | Recurrence of T1D in Pancreas Transplantation | 400 | May 2024 |
NCT01957696 | A Prospective, Observational Study in Pancreatic Allograft Recipients: The Effect of Risk Factors, Immunosuppressive Level and the Benefits of Scheduled Biopsies - on Surgical Complications, Rejections and Graft Survival | 80 | Oct 2028 |
Unpublished | |||
NCT00238693 | Transplant Registry: Patients Who May Require Transplantation and Those Who Have Undergone Transplantation of Liver, Kidney and/or Pancreas | 13,767 | Aug 2018 |
NCT03921593 | Prospective Longitudinal Observational Study on Insulin Dependent Diabetic Patients Undergoing Any Form of Solid Organ Pancreas Transplantation Aimed to Clarify Quality of Life Changes After Pancreas Transplantation | 110 | Mar 2022 |
NCT: national clinical trial.
Codes
|
Number
|
Description
|
CPT
|
48550
|
Donor pancreatectomy (including cold preservation), with or without duodenal segment for transplantation
|
|
48551
|
Backbench standard preservation of cadaver donor
pancreas allograft prior to transplantation, including dissection of allograft from surrounding tissues, splenectomy, duodenotomy, ligation of bile duct, ligation of mesenteric vessels, and Y-graft arterial anastomoses from iliac artery to superior mesenteric artery and to splenic artery
|
|
48552
|
Backbench reconstruction of cadaver donor pancreas allograft prior to transplantation, venous anastomosis, each
|
|
48554
|
Transplantation of pancreatic allograft
|
HCPCS
|
S2065
|
Simultaneous pancreas kidney transplantation
|
ICD-10-CM
|
E10.10-E10.11
|
Type I diabetes mellitus with ketoacidosis, code range
|
|
E10.21-E10.29
|
Type I diabetes mellitus with kidney complications, code range
|
|
E10.641-E10.649
|
Type I diabetes mellitus with hypoglycemia, code range
|
|
E10.69
|
Type I diabetes mellitus other specified complications
|
|
E10.8
|
Type I diabetes mellitus with unspecified complications
|
|
T86.890-T86.899
|
Complications of other transplanted tissue, code range
|
|
Z90.5
|
Acquired absence of kidney
|
ICD-10-PCS
|
0FYG0Z0, 0FYG0Z1
|
Surgical, hepatobiliary system & pancreas, transplantation, open, code by qualifier (allogeneic or syngeneic)
|
|
0FSG0ZZ, 0FSG4ZZ
|
Surgical, hepatobiliary system & pancreas, reposition, code by approach (open or percutaneous endoscopic)
|
Type of service
|
Surgery
|
|
Place of service
|
Inpatient
|
|
Date
|
Action
|
Description
|
09/08/23
|
Annual Review
|
Policy updated with literature review through June 30, 2023; no references added. Policy statements unchanged.
|
09/06/22
|
Annual review
|
Policy updated with literature review through June 21, 2022; no references added. Minor editorial refinements to policy statements; intent unchanged.
|
09/09/21
|
Annual review
|
Policy updated with literature review through June 22, 2021; references added; Policy statements unchanged.
|
09/09/20
|
Annual review
|
Policy updated with literature review through June 24, 2020; references added; Policy statements unchanged.
|
09/05/19
|
Annual review
|
Policy updated with literature review through June 10, 2019; references added. Policy statements unchanged.
|
09/01/17
|
|
|
09/20/16
|
|
|
02/12/15
|
|
|
02/13/14
|
|
|
03/01/13
|
|
|
05/02/12
|
|
|
02/09/12
|
|
|
05/06/09
|
|
iCES
|
04/09/08
|
|
|
02/16/07
|
|
|
11/03/06
|
|
|
01/22/04
|
Created
|
New policy
|