Medical Policy: 07.03.01 
Original Effective Date: October 2004 
Reviewed: October 2016 
Revised: December 2014 


Benefit Application:

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.


Description:

Autologous islet cell transplantation performed in conjunction with pancreatectomy, is proposed to reduce the likelihood of insulin-dependent diabetes. Allogeneic islet cell transplantation is being investigated as a treatment or cure for patients with type 1 diabetes.

The islet cells come from the patient (autologous transplant) or from a cadaveric donor (allogeneic transplant). Islet cell transplantation may benefit an individual who is without a functioning pancreas. Currently, only individuals with either chronic pancreatitis or type 1 diabetes mellitus have been subject to clinical investigations. 

 

Chronic Pancreatitis

Chronic pancreatitis is inflammation of the pancreas that does not heal or improve, it gets worse over time and leads to permanent damage. Chronic pancreatitis eventually impairs an individual’s ability to digest food and make pancreatic hormones. Individuals with chronic pancreatitis can experience intractable pain that can only be relieved with a total or near total pancreatectomy. However, the pain relief must be balanced against the certainty that the individual will be rendered an insulin-dependent diabetic.

 

Autologous islet cell transplantation has been investigated as a technique to prevent this serious morbidity of surgically induced diabetes due to the removal of the individual’s pancreas. The transplant is generally performed during the pancreatectomy procedure, and the islet cells are isolated from the resected pancreas using enzymes, and a suspension of the cells is injected into the portal vein of the patient’s liver. Once implanted, the beta cells in these islets begin to make and release insulin. Because the body recognizes these islet cells as its own, there is no rejection of these cells by the patient’s body.

  

Although the published literature regarding autologous islet cell transplant is limited, the procedure appears to significantly decrease the occurrence of surgically induced diabetes after total or near total pancreatectomy in patients with chronic pancreatitis. Also, this procedure is not associated with serious complications itself and is performed in patients who are already undergoing a pancreatectomy procedure. Autologous islet cell transplantation may be considered medically necessary and a adjunct to a total or near total pancreatectomy in patients with chronic pancreatitis. The evidence is insufficient to demonstrate the efficacy of autologous islet cell transplantation performed for any other indication.

 

Type 1 Diabetes Mellitus

Type 1 diabetes is a chronic illness characterized by the body’s inability to produce insulin due to the autoimmune destruction of the beta cells in the pancreas. Islet cell autoantibodies (ICAs) are theorized to cause the individual to reject their own islet cells, leading to insulin deficiency. Individuals with type 1 diabetes do not have viable beta cells and therefore, cannot receive an autologous islet cell transplant.

 

Allogeneic islet cell transplant has been proposed as a treatment for patients with type 1 diabetes to restore normoglycemia (normal glucose levels) and ultimately to reduce or eliminate the long-term complications of diabetes such as retinopathy, neuropathy, nephropathy, and cardiovascular disease. Islet cell transplantation potentially offers an alternative to whole-organ pancreas transplantation.  Therefore, islet transplantation has generally been reserved for patients with frequent and severe metabolic complications who have consistently failed to achieve control with insulin-based management.

 

Allogeneic islet cell transplant is a procedure in which islets are obtained from deceased organ donor and are purified, processed and transferred into the transplant patient. A limitation of allogeneic islet cell transplantation is that 2 or more donor organs are usually required for successful transplantation. A pancreas that is rejected for whole-organ transplant is typically used for islet transplantation. Transplant patients typically receive two infusions with an average of 400,000 to 500,000 islets per infusion. Once implanted in the liver, the beta cells in these islets begin to make and release insulin. The patient will be started on immuosuppressive therapy to prevent allograft rejection. 

 

The techniques for allogeneic islet cell transplants are evolving, and the impact on the net health outcome for patients with type 1 diabetes, not otherwise undergoing surgery, is still uncertain. Longer follow up with larger numbers of patients is needed before conclusions can be drawn about the long-term safety of allogeneic islet cell transplantation and its impact on diabetes mellitus. and associated complications.  Therefore, allogeneic islet cell transplantation is considered investigational for all indications. 

 

Practice Guidelines and Position Statements

American Diabetes Association

In 2004, the American Diabetes Association issued a position statement on pancreas transplantation in patients with type 1 diabetes which included the following recommendation: Pancreatic islet cell transplants hold significant potential advantagese over whole gland transplants. However, at this time, islet cell transplantation is an experimental procedure, also requiring systemic immunosuppression, and should be performed only within the setting of controlled research studies.

 

National Institute for Health and Clinical Excellence (NICE)

In 2008 the National Institute for Health and Clinical Excellence issued guidance on allogeneic pancreatic islet cell transplantation for type 1 diabetes mellitus which states: The evidence on allogeneic pancreatic islet cell transplantation for type 1 diabetes mellitus shows short-term efficacy with some evidence of long-term efficacy. The evidence on safety shows that serious complications may occur as a result of this procedure. The long-term immunosuppression required is also associated with a risk of adverse events.

During consent, clinicians should ensure that patients understand the potential complications of the procedure and uncertainty about is efficacy in the long term.

Further audit and research should address the effect ot the procedure on quality of life and its long term efficacy, particularly in relation to the complications of diabetes.  

In 2008 the National Institute for Health and Clinical Excellence issued guidance on autologous pancreatic islet cell transplantation for improved glycemic control after pancreatectomy which states: The current evidence on autologous pancreatic islet cell transplantation for improved glycemic control after pancreatectomy shows some short term efficacy, although most patients require insulin therapy in the long term. The reported complications result mainly from the major surgery involved in the pancreatectomy (rather than from the islet cell transplantation).

During consent, clinicians should ensure that patients understand that they may require insulin therapy in the long term. 

 

American Society of Transplantation

In 2013 the American Society of Transplantation issued a 3rd edition guideline on the transplantation infectious diseases that includes criteria for transplantation for HIV infected individuals. The criteria for transplantation for HIV infected individuals for kidney/pancreas transplants includes the following:

  • Meet center specific inclusion criteria
  • CDC count >200 cells/uL during 3 months before transplantation
  • Undetectable HIV viral load while receiving antiretroviral therapy
  • Documented compliance with a stable antiretroviral regimen
  • Absence of active opportunistic infection and malignancy
  • Absence of chronic wasting or severe malnutrition
  • History of hepatitis B or C with lack of evidence of advanced fibrosis or cirrhosis
  • Acceptance of life-long pneumocystis prophylaxis
  • Donor free of hepatitis C
  • Appropriate follow up with providers experienced in the management of HIV
  • Ready access to immunosuppressive medication therapeutic drug monitoring

Organ Procurement and Transplantation Network (OPTN)

Islet Registration Status Effective October 2016

A transplant hospital may register an islet candidate on the waiting list with an active status if the candidate meets either of the following requirements:

  • Is insulin dependent
  • Has a hemoglobin A1c (HcA1c) value greater than 6.5%

An islet candidate that does not meet either of these requirements must have an inactive status on the waiting list. If the transplant hospital changes a candidate’s status from inactive to active, the transplant hospital must document that the candidate met one of the above requirements.  

If the candidate is active and is insulin dependent, then the transplant hospital must document in the candidate’s medical record that the candidate’s insulin status and HbA1c value. The transplant hospital must use the most recent HbA1c test performed within the last six months when determining whether the candidate meets criteria for active status.

 

Regulatory Status

Islet cells are subject to regulation by the U.S. Food and Drug Administration (FDA), which classifies allogeneic islet cells transplantation as somatic cell therapy requiring pre-market approval. Islet cells also meet the definition of a drug under the Federal Food, Drug and Cosmetic Act. Clinical studies to determine safety and effectiveness outcomes of allogeneic islet transplantation must be conducted under FDA investigational new drug regulation. At least 35 investigational new drug applications have been submitted to the FDA, no center has submitted a biologics license application.


Prior Approval:

 

Not applicable


Policy:

  • See also Medical Policy 07.03.09 Pancreas Transplants (including simultaneous pancreas-kidney), pancreas alone, and pancreas after kidney)
  • See also Medical Policy 01.01.26 Artificial Pancreas Device System 

 

Autologous Pancreas Islet Cell Transplantation

Autologous pancreas islet cell transplantation may be considered medically necessary as an adjunct to a total or near-total pancreatectomy in patients with chronic pancreatitis.

 

Autologous pancreas islet cell transplantation is considered investigational when the above criteria is not met and for all other indications because the safety and/or effectiveness of this procedure for all other indications can not be established based on available peer reviewed literature. 

 

Allogeneic Pancreas Islet Cell Transplantation

Allogeneic pancreas islet cell transplantation is considered investigational for all indications including the treatment of type 1 diabetes.

 

The techniques for allogeneic islet cell transplants are evolving; the impact on net health outcomes is still uncertain. 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 complications of diabetes mellitus, thus the procedure is considered investigational



Procedure Codes and Billing Guidelines:

  • To report provider services, use appropriate CPT* codes, Modifiers, Alpha Numeric (HCPCS level 2) codes, Revenue codes, and/or diagnosis codes.
  • 48160 Pancreatectomy, total or subtotal, with autologous transplantation of pancreas or pancreatic islet cells.
  • 48999 Unlisted procedure, pancreas (when specified as pancreatic islet cell transplantation)
  • G0341 Percutaneous islet cell transplant, includes portal vein catheterization and infu
  • G0342 Laparoscopy for islet cell transplant, includes portal vein catheterization and infusion
  • G0343 Laparotomy for islet cell transplant, includes portal vein catheterization and infusion
  • S2102 Islet cell tissue transplant from pancreas; allogeneic  

Selected References:

  • Piper MA, Seidenfeld J, Aronson N. Islet Transplantation in Type 1 Diabetes Mellitus. Evidence Report/Technology Assessment No. 98 (Prepared by the Blue Cross and Blue Shield Association Technology Evaluation Center Evidence-based Practice Center). AHRQ Publication No. 04-E017-2. Rockville, MD: Agency for Healthcare Research and Quality. April 2004.
  • Wahoff DC, Papalois BE, Najarian JS, et al. Autologous islet transplantation to prevent diabetes after pancreatic resection. Ann Surg 1995; 222(4):562-79.
  • Robertson RP, Lanz KJ, Sutherland DE, et al. Prevention of diabetes for up to 13 years by auto islet transplantation after pancreatectomy for chronic pancreatitis. Diabetes 2001; 50(1):47-50.
  • TARGET [database online]. Plymouth Meeting (PA): ECRI; 2005 March. Islet cell transplantation for type 1 diabetes.
  • Frank A, Deng S, Huang X et al. Transplantation for type 1 diabetes: comparison of vascularized whole-organ pancreas with isolated pancreatic islets. Ann Surg 2004 Oct; 240(4):631-40.
  • Robertson RP. Islet transplantation as a treatment for diabetes-a work in progress. NEJM. 2004; 350(7):694-705.
  • TARGET [database online]. Plymouth Meeting (PA): ECRI; 2005 March. (Updated 2005 June 27) Islet cell transplantation for type 1 diabetes.
  • Frank A, Deng S, Huang X et al. Transplantation for type 1 diabetes: comparison of vascularized whole-organ pancreas with isolated pancreatic islets. Ann Surg 2004 Oct; 240(4):631-40.
  • Robertson RP. Islet transplantation as a treatment for diabetes-a work in progress. NEJM. 2004; 350(7):694-705.
  • ECRI. Islet cell transplantation for the treatment of Type 1 diabetes. Plymouth Meeting (PA): ECRI Health Technology Assessment Information Service; 2005 Oct. 80 p. (Windows on medical technology; no. 130).
  • Robertson RP, Davis C, Larsen J, Stratta R, Sutherland DE, American Diabetes Association.  Position statements: Pancreas and islet transplantation in type 1 diabetes. Diabetes Care. 2006 Apr;29(4):935.
  • National Institutes of Health (US). Collaborative Islet Transplant Registry: Annual Report. Bethesda, MD: National Institute of Diabetes and Digestive Kidney Diseases External SiteSeptember 2008. Accessed March 16, 2009.
  • Jindal RM, Ricordi C, Shriver CD. Autologous pancreatic islet transplantation for severe trauma. N Engl J Med. 2010 Apr 22;362(16):1550.
  • Halban PA, German MS Kahn SE et al. Current status of islet cell replacement and regeneration therapy. J Clin Endocrinol Metab. 2010 Mar;95(3):1034-43. Epub 2010 Jan 8.
  • Gremizzi C, Vergani A, Paloschi V et al. Impact of pancreas transplantation of type 1 diabetes-related complications. Curr Opin Organ Transplant. 2010 Feb; 15(1):119-23.
  • Thompson DM, Meloche M, Ao Z et al. Reduced progression of diabetic microvascular complications with islet cell transplantation compared with intensive medical therapy. Transplantation. 2011 Feb 15;91(3):373-8.
  • Posselt AM, Szot GL, Frassetto LA et al. Islet transplantation in type 1 diabetic patients using calcineurin inhibitor-free immunosuppressive protocols based on R-cell adhesion or costimulation blockade. Transplantation. 2010 Dec 27;90(12):1595-601.
  • Posselt AM, Bellin MD, Tavakol M et al. Islet transplantation in type 1 diabetes using an immunosuppressive protocol based on the anti-LFA-1 antibody efalizumab. Am J Transplant. 2010 Aug;10(8):1870-80.
  • Aguayo-Mazzucato C, Bonner-Weir S. Stem cell therapy for type 1 diabetes mellitus. Nat Rev Endocrinol. 2010 Mar;6(3):139-48.
  • de Vos P, Spasojevic M, Faas MM. Treatment of diabetes with encapsulated islets. Adv Exp Med Biol. 2010; 670:38-53.
  • Bramis K, Gordon-Weeks AN, Friend PJ et al. Systematic review of total pancreatectomy and islet autotransplantation for chronic pancreatitis. Br J Surg. 2012 Jun;99(6):761-6. doi: 10.1002/bjs.8713. Epub 2012 Mar 20.
  • Dong M, Parsaik AK, Erwin PJ et al. Systematic review and meta-analysis: islet autotransplantation after pancreatectomy for minimizing diabetes. Clin Endocrinol (Oxf). 2011 Dec;75(6):771-9. doi: 10.1111/j.1365-2265.2011.04121.x.
  • Sutherland DE, Radosevich DM, Bellin MD et al. Total pancreatectomy and islet transplantation for chronic pancreatitis. J AM Coll Surg. 2012 Apr;214(4):409-24. Epub 2012 Mar 6.
  • Desai CS, Stephenson DA, Khan KM et al. Novel techniques of total pancreatectomy before autologous islet transplants in chronic pancreatitis patients. J AM Coll Surg. 2011 Dec;213(6):e29-34. Epub 2011 Oct 13.
  • Matsumoto S. Clinical allogeneic and autologous islet cell transplantation: update. Diabetes Metab J. 2011 Jun;35(3):199-206. Epub 2011 Jun 30.
  • Jamiolkowski RM, Guo LY, Li YR et al. Islet transplantation in type 1 diabetes mellitus. Yale J Biol Med. 2012 Mar;85(1):37-43. Epub 2012 Mar 29.
  • ECRI Hotline response: Indications and contraindications for Islet Cell Transplantation for Treating Type 1 Diabetes ECRI Institute 2012 Nov.
  • National Institute for Health and Clinical Excellence (NICE) External Site Autologous Pancreatic Islet Cell Transplantation for Improved Glycaemic Control after Pancreatectomy. September 2008.
  • National Institute for Health and Clinical Excellence (NICE) External Site Allogeneic Pancreatic Islet Cell Transplantation for Type 1 Diabetes Mellitus. April 2008.
  • National Diabetes Information Clearinghouse External Site(NDIC). Pancreatic Islet Transplantation.
  • UNOS Pancreas Allocation Policy. September 1, 2013.
  • CMS External SiteNational Coverage Determination for Pancreas Transplants (260.3).
  • UpToDate External SitePancreas and Islet Transplantation in Diabetes Mellitus. R. Paul Robertson, M.D.. Topic last updated March 7, 2016.
  • UpToDate External SiteTreatment of Chronic Pancreatitis. Steven D. Freedman, M.D., PhD. Topic last updated October 8, 2013.
  • American Diabetes Association External SiteIslet Transplantation.
  • ECRI External SiteHotline Response: Islet Cell Transplantation for Treating Type 1 Diabetes. Updated May 27, 2015.
  • Medscape External SiteType 1 Diabetes Mellitus, updated October 21, 2014. 
  • National Institute for Health and Clinical Excellence (NICE) External Site Type 1 Diabetes in Adults: Diagnosis and Management (NG17), August 2015.
  • Al-Adra. Gill RS, et. al. Single Donor Islet Transplantation and Long Term Insulin Dependence in Select Patients with Type 1 Diabetes Mellitus. Transplantation 2014 Nov 15:98(9):1007-12
  • Anazawa T, Saito T, et. al. Long Term Outcomes of Clinical Transplantation of Pancreatic Islets with Uncontrolled Donors after Cardiac Death: A Multicenter Experience in Japan. Transplant Proc. 2014 Jul-Aug:46(6):1980-4
  • Brooks AM, Oram R, et. al. Demonstration of an Intrinsic Relationship Between Endogenous C-Peptide Concentration and Determinats of Glycemic Control in Type 1 Diabetes Following Islet Transplantation. Diabetes Care 2015 Jan;38(1):105-12
  • Byrne ML, Hopkins D, et. al. Outcomes for Adults with Type 1 Diabetes Referred with Severe Hypoglycaemia and/or Referred for Islet Transplantation to a Specialist Hypoclycaemia Service. Horm Metab Res 2015 Jan;47(1):9-15
  • Caiazzo R, Vantyghem MC, et. al. Impact of Procedure-Related Complications on Long-Term Islet Transplantation Outcome. Transplantation 2015 May:99(5):979-84
  • Colling KP, Blondet JJ, et. al. Positive Sterility Cultures of Transplant Solutions During Pancreatic Islet Autotransplantation are Associated Infrequently with Clinical Infection. Surg Infect (Larchmt). 2015 Apr;16(2):115-23
  • Georgiey G, Beltran Del Rio M, et. al. Patient Quality of Life and Pain Improve after Autologous Islet Transplantation (AIT) for Treatment of Chronic Pancreatitis: 53 Patient Series at the University of Arizona. Pancreatology 2015 Jan-Feb;15(1):40-5
  • Qi M, Kinzer K, et. al. Five Year Follow-Up of Patients with Type 1 Diabetes Transplanted with Allogeneic Islets: The UIC Experience. Acta Diabetol. 2014 Oct;51(5):833-43
  • Tai Ds, Shen N, et. al. Autologous Islet Transplantation with Remote Islet Isolation after Pancreas Resection for Chronic Pancreatitis. Jama Surg 2015 Feb;150(2):118-24
  • Thakor AS, Sangha BS. et. al. Percutaneous Autologous Pancreatic Islet Cell Transplantation for Traumatic Pancreatic Injury. J Clin Endocrinol Metab 2015 Apr;100(4):1230-3
  • American Diabetes Association External Site Pancreas Transplantation Diabetes Care 2004 Jan;27:s105-S105.
  • Rickels MR, Kong SM, Fuller C, et. al. Improvement in insulin sensitivity after human islet transplantation for type 1 diabetes. J Clin Endocrinol Metab 2013 Nov;98(11):E1780-5. PMID 24085506
  • Wilson GC, Sutton JM, Abbott DE, et. al. Long-term outcomes after total pancreatectomy and islet cell autotransplantation: is it durable operation? Ann Surg 2014 Oct;260(4):659-65. PMID 25203883 
  • Organ Procurement and Transplant Network (OPTN) External Site Allocation of Kidney-Pancreas and Islets. October 2016.
  • Blumberg E.A., Rogers C.C., The American Society of Transplantation Infectious Diseases Guidelines 3rd Edition, Human Immunodeficiency Virus in Solid Organ Transplantation. American Journal of Transplantation Volume 13, Issue s4 March 2013 Pages 169-178
  • ECRI External Site Health Technology Forecast News Brief. Islet cell transplantation may improve hypoglycemia awareness in patients with type 1 diabetes, Published April 26, 2016.
  • Centers for Medicare and Medicaid Services (CMS) External Site National Coverage Determination (NCD) for pancreas transplants (260.3). Effective April 26, 2006.
  • UpToDate External Site Total Pancreatectomy. Michael D. Kluger M.D., MPH, James Less, M.D., John Chabot M.D., Topic last updated April 26, 2016.
  • Wu Q, Zhang M, Qin Y, et. al. Systematic review and meta-analysis of islet autotransplantation after total pancreatectomy in chronic pancreatitis patients, Endocr J 2015;62(3):227-34. PMID 25735805
  • Chinnakotla S, Radosevich DM, Dunn TB, et. al. Long-term outcomes of total pancreatectomy and islet auto transplantation for hereditary/genetic pancreatitis. J Am Coll Surg 2014 Apr;218(4):530-43. PMID 24655839

Policy History:

  • October 2016 - Annual Review, Policy Renewed 
  • November 2015 - Annual Review, Policy Renewed
  • December 2014 - Annual Review, Policy Revised
  • February 2014 - Annual Review, Policy Revised
  • March 2013 - Annual Review, Policy Renewed
  • July 2012 - Annual Review, Policy Renewed
  • August 2011 - Annual Review, Policy Renewed

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.

*Current Procedural Terminology © 2012 American Medical Association. All Rights Reserved.