KEY POINTS:

The most recent literature review was performed through July 30, 2024.

Summary of Evidence

For individuals with chronic pancreatitis undergoing total or near total pancreatectomy who receive autologous pancreas islet transplantation, the evidence includes nonrandomized studies and systematic reviews. Relevant outcomes are overall survival (OS), change in disease status, medication use, resource utilization, and treatment-related morbidity. Autologous islet transplants are performed in the context of total or near total pancreatectomies to treat intractable pain for chronic pancreatitis. The procedure appears to significantly decrease the incidence of diabetes after total or near total pancreatectomy in individuals with chronic pancreatitis. Also, this islet procedure itself is not associated with serious complications and is performed in patients who are already undergoing a pancreatectomy procedure. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.

For individuals with type 1 diabetes who receive allogeneic pancreas islet transplantation, the evidence includes a randomized controlled trial, registry studies, and systematic reviews. Relevant outcomes are overall survival, change in disease status, medication use, resource utilization, and treatment-related morbidity. Results of a 2018 randomized trial have suggested some reduction in the number of severe hypoglycemic incidence annually, but limited follow-up and other trial limitations reduce the certainty in conclusions drawn. A wide range of insulin independence has been reported in case series. There is conflicting evidence whether allogeneic islet transplantation reduces long-term diabetic complications. Long-term comparative studies are required to determine the effects of allogeneic islet transplantation in type 1 diabetics. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Practice Guidelines and Position Statements

National Institute for Health and Care Excellence

In 2008, National Institute for Clinical Excellence published guidance indicating the evidence on allogeneic pancreatic islet cell transplantation for type I diabetes has shown that serious procedure-related complications may occur, and the long term immunosuppression required is associated with risk of adverse events. A related 2008 guidance addressed autologous islet cell transplantation for improved glycemic control after pancreatectomy and stated that studies have shown “some short-term efficacy, although most patients require insulin therapy in the long term… complications result mainly from the major surgery involved in pancreatectomy (rather than from the islet cell transplantation).”

American Diabetes Association

In 2024, the American Diabetes Association standards of medical care recommended autologous islet cell transplantation be considered in individuals undergoing total pancreatectomy for chronic pancreatitis to prevent post-surgical diabetes.  The standards of care note that islet cell transplantation may have a role in type 1 diabetes. Because of the need for immunosuppressive agents post-transplantation, the guideline notes that transplantation in type 1 diabetes should be reserved for individuals also undergoing renal transplantation or experiencing recurrent ketoacidosis with severe hypoglycemia despite intensive management.

International Consensus Guidelines for Chronic Pancreatitis

In 2020, the International Consensus Guidelines for Chronic Pancreatitis panel released a statement on the role of total pancreatectomy and islet transplant in individuals with chronic pancreatitis. The panel stated that islet transplant should be considered for individuals undergoing total pancreatectomy due to the potential for insulin independence and better long-term glycemic outcomes compared to pancreatectomy alone (weak recommendation based on low quality evidence). However, there is not enough information to definitively conclude when transplant should be performed relative to other interventions. Major indications for pancreatectomy with islet transplant include debilitating pain or recurrent pancreatitis episodes that diminish quality of life (strong recommendation based on low quality evidence). Contraindications to pancreatectomy with islet transplant include active alcoholism, pancreatic cancer, end-stage systemic illness, or psychiatric illness or socioeconomic status that would hinder either the procedure itself or posttransplant care (strong recommendation based on low quality evidence). Pancreatectomy with islet transplant improves quality of life, opioid use, and pancreatic pain in this population, but evidence about the effect on healthcare utilization is limited.

U.S Preventive Services Task Force Recommendations

Not Applicable

KEY WORDS:

Allogeneic islet cell transplantation, islet cell transplantation, pancreas, autologous islet cell transplantation, auto islet transplantation

APPROVED BY GOVERNING BODIES:

The U.S. Food and Drug Administration (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.

Allogeneic islet cells are included in these regulations. No allogeneic islet cell product is currently approved in the United States, but a biologic license application is currently under consideration by the FDA, and the Cellular, Tissue and Gene Therapies Advisory Committee voted in favor of approving the product (donislecel, purified allogeneic deceased donor pancreatic islet cells) in April 2021.

BENEFIT APPLICATION:

Coverage is subject to member’s specific benefits.  Group-specific policy will supersede this policy when applicable.

ITS: Home Policy provisions apply

FEP: Special benefit consideration may apply. Refer to member’s benefit plan.

CURRENT CODING: 

CPT Codes:  

HCPCS Codes:

REFERENCES:

1. Abu-El-Haija M, Anazawa T, Beilman GJ, et al. The role of total pancreatectomy with islet autotransplantation in the treatment of chronic pancreatitis: A report from the International Consensus Guidelines in chronic pancreatitis. Pancreatology. Jun 2020; 20(4): 762-771.
2. Ahmad SA, Lowy AM, Wray CJ, et al. Factors associated with insulin and narcotic independence after islet autotransplantation in patients with severe chronic pancreatitis. J Am Coll Surg. Nov 2005; 201(5): 680-7.
3. American Diabetes Association. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes-2021 .Diabetes Care. Jan 2021; 44(Suppl 1): S111-S124.
4. American Diabetes Association. 4. Comprehensive Medical Evaluation and Assessment of Comorbidities: Standards of Medical Care inDiabetes-2021 . Diabetes Care. Jan 2021; 44(Suppl 1): S40-S52.
5. Argo JL, Contreras JL, Wesley MM, et al. Pancreatic resection with islet cell autotransplant for the treatment of severe chronic pancreatitis. Am Surg. Jun 2008; 74(6): 530-6; discussion 536-7.
6. Barton FB, Rickels MR, Alejandro R et al. Improvement in outcomes of clinical islet transplantation: 1999-2010. Diabetes Care 2012; 35(7):1436-1445.
7. Berney T, Mathe Z, Bucher P, et al. Islet autotransplantation for the prevention of surgical diabetes after extended pancreatectomy for the resection of benign tumors of the pancreas. Transplant Proc. May 2004; 36(4): 1123-4.
8. Cameron JL, Mehigan DG, Broe PJ, et al. Distal pancreatectomy and islet autotransplantation for chronic pancreatitis. Ann Surg. Mar 1981; 193(3): 312-7.
9. 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. Apr 2014; 218(4):530-543.
10. Chinnakotla S, Beilman GJ, Dunn TB, et al. Factors Predicting Outcomes After a Total Pancreatectomy and Islet Autotransplantation Lessons Learned From Over 500 Cases. Ann Surg. Oct 2015; 262(4): 610-22.
11. Dixon J, DeLegge M, Morgan KA, et al. Impact of total pancreatectomy with islet cell transplant on chronic pancreatitis management at a disease-based center. Am Surg. Aug 2008; 74(8): 735-8.
12. Dong M, Parsaik AK, Erwin PJ et al. Systematic review and meta-analysis: islet autotransplantation after pancreatectomy for minimizing diabetes. Clin Endocrinol (Oxf). Dec 2011; 75(6):771-779.
13. ElSayed NA, Aleppo G, Aroda VR, et al. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes-2023.Diabetes Care. Jan 01 2023; 46(Suppl 1): S140-S157.
14. ElSayed NA, Aleppo G, Aroda VR, et al. 4. Comprehensive Medical Evaluation and Assessment of Comorbidities: Standards of Care inDiabetes-2023. Diabetes Care. Jan 01 2023; 46(Suppl 1): S49-S67.
15. Fan CJ, Hirose K, Walsh CM, et al. Laparoscopic Total Pancreatectomy With Islet Auto transplantation and Intraoperative Islet Separation as a Treatment for Patients With Chronic Pancreatitis. JAMA Surg. Jun 01 2017; 152(6): 550-556.
16. Fontana I, Arcuri V, Tommasi GV, et al. Long-term follow-up of human islet autotransplantation. Transplant Proc. Apr 1994; 26(2):581.
17. Food and Drug Administration (FDA). Guidance for Industry: Considerations for Allogeneic Pancreatic Islet Cell Products. 2009; www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/ CellularandGeneTherapy/UCM182441.pdf.
18. Food and Drug Administration Center for Biologics Evaluation and Research. Cellular, Tissue and Gene Therapies Advisory Committee meeting minutes. April 15, 2021. www.fda.gov/media/148461/download.
19. Gangemi A, Salehi P, Hatipoglu B, et al. Islet transplantation for brittle type 1 diabetes: the UIC protocol. Am J Transplant. Jun 2008;8(6): 1250-61.
20. Garcea G, Pollard CA, Illouz S, et al. Patient satisfaction and cost-effectiveness following total pancreatectomy with islet cell transplantation for chronic pancreatitis. Pancreas. Mar 2013; 42(2): 322-8.
21. Georgiev G, Beltran del Rio M, Gruessner A, 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; 15(1): 40-5.
22. Gruessner RW, Cercone R, Galvani C, et al. Results of open and robot-assisted pancreatectomies with autologous islet transplantations: treating chronic pancreatitis and preventing surgically induced diabetes. Transplant Proc. Jul-Aug 2014; 46(6):1978-9.
23. Health Quality Ontario. Pancreas islet transplantation for patients with type 1 diabetes mellitus: a clinical evidence review. Ont Health Technol Assess Ser. 2015; 15(16):1-84.
24. Hering BJ, Clarke WR, Bridges ND, et al. Phase 3 Trial of Transplantation of Human Islets in Type 1 Diabetes Complicated by Severe Hypoglycemia. Diabetes Care. Jul 2016; 39(7): 1230-40.
25. Hinshaw DB, Jolley WB, Hinshaw DB, et al. Islet autotransplantation after pancreatectomy for chronic pancreatitis with a new method of islet preparation. Am J Surg. Jul 1981; 142(1): 118-22.
26. Jindal RM, Fineberg SE, Sherman S, et al. Clinical experience with autologous and allogeneic pancreatic islet transplantation. Transplantation. Dec 27 1998; 66(12): 1836-41. 
27. Jung HS, Choi SH, Kim SJ, et al. Delayed improvement of insulin secretion after autologous islet transplantation in partially pancreatectomized patients. Metabolism. Nov 2009; 58(11): 1629-35.
28. Kempeneers MA, Scholten L, Verkade CR, et al. Efficacy of total pancreatectomy with islet autotransplantation on opioid and insulin requirement in painful chronic pancreatitis: A systematic review and meta-analysis. Surgery. Sep 2019; 166(3): 263-270.
29. Markmann JF, Rickels MR, Eggerman TL, et al. Phase 3 trial of human islet-after-kidney transplantation in type 1 diabetes. Am J Transplant. Apr 2021; 21(4): 1477-1492.
30. Mokadem M, Noureddine L, Howard T, et al. Total pancreatectomy with islet cell transplantation vs intrathecal narcotic pump infusion for pain control in chronic pancreatitis. World J Gastroenterol. Apr 28 2016; 22(16): 4160-7.
31. Morgan KA, Lancaster WP, Owczarski SM, et al. Patient Selection for Total Pancreatectomy with Islet Autotransplantation in the Surgical Management of Chronic Pancreatitis. J Am Coll Surg. Apr 2018; 226(4): 446-451.
32. National Institute for Health and Care Excellence (NICE). Allogenic pancreatic islet cell transplantation for type 1 diabetes mellitus [IPG257]. 2008; www.nice.org.uk/Guidance/IPG257.
33. National Institute for Health and Care Excellence (NICE). Autologous pancreatic islet cell transplantation for improved glycemic control after pancreatectomy [IPG274]. 2008; www.nice.org.uk/Guidance/IPG274.
34. Oberholzer J, Triponez F, Mage R, et al. Human islet transplantation: lessons from 13 autologous and 13 allogeneic transplantations. Transplantation. Mar 27 2000; 69(6): 1115-23. 
35. Qi M, Kinzer K, Danielson KK, et al. Five-year follow-up of patients with type 1 diabetes transplanted with allogeneic islets: the UIC experience. Acta Diabetol. Oct 2014; 51(5): 833-43
36. Quartuccio M, Hall E, Singh V, et al. Glycemic Predictors of Insulin Independence After Total Pancreatectomy With Islet Autotransplantation. J Clin Endocrinol Metab. Mar 01 2017; 102(3): 801-809.
37. Rabkin JM, Olyaei AJ, Orloff SL, et al. Distant processing of pancreas islets for autotransplantation following total pancreatectomy. Am J Surg. May 1999; 177(5): 423-7.
38. Rastellini C, Shapiro R, Corry R, et al. Treatment of isolated pancreatic islets to reverse pancreatectomy-induced and insulin dependent type I diabetes in humans: a 6-year experience. Transplant Proc. Feb-Mar 1997; 29(1-2): 746-7.
39. Shahbazov R, Yoshimatsu G, Haque WZ, et al. Clinical effectiveness of a pylorus-preserving procedure on total pancreatectomy with islet autotransplantation. Am J Surg. Jun 2017; 213(6): 1065-1071.
40. Solomina J, Gołębiewska J, Kijek MR, et al. Pain Control, Glucose Control, and Quality of Life in Patients With Chronic Pancreatitis After Total Pancreatectomy With Islet Autotransplantation: A Preliminary Report. Transplant Proc. Dec 2017;49(10): 2333-2339.
41. Sutherland DE, Gruessner AC, Carlson AM et al. Islet autotransplant outcomes after total pancreatectomy: a contrast to islet allograft outcomes. Transplantation 2008; 86(12):1799-1802.
42. Sutherland DE, Radosevich DM, Bellin MD et al. Total pancreatectomy and islet autotransplantation for chronic pancreatitis. J Am Coll Surg 2012; 214(4):409-424.
43. Tai DS, Shen N, Szot GL, et al. Autologous islet transplantation with remote islet isolation after pancreas resection for chronicpancreatitis. JAMA Surg. Feb 2015; 150(2):
44. Takita M, Lara LF, Naziruddin B, et al. Effect of the Duration of Chronic Pancreatitis on Pancreas Islet Yield and Metabolic Outcome Following Islet Autotransplantation. J Gastrointest Surg. Jul 2015; 19(7): 1236-46. 
45. Takita M, Naziruddin B, Matsumoto S, et al. Variables associated with islet yield in autologous islet cell transplantation for chronic pancreatitis. Proc (Bayl Univ Med Cent). Apr 2010; 23(2): 115-20.
46. 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; 91(3): 373-378.
47. Tillou JD, Tatum JA, Jolissaint JS, et al. Operative management of chronic pancreatitis: A review. Am J Surg. Aug 2017;214(2): 347-357.
48. Toledo-Pereyra LH. Islet cell autotransplantation after subtotal pancreatectomy. Arch Surg. Jul 1983; 118(7): 851-8. 
49. U.S. Food & Drug Administration (FDA). FDA Approves First Cellular Therapy to Treat Patients with Type 1 Diabetes. June 28, 2023. www.fda.gov/news-events/press-announcements/fda-approves-first-cellular-therapy-treat-patients-type1-diabetes
50. Vantyghem MC, de Koning EJP, Pattou F, et al. Advances in β-cell replacement therapy for the treatment of type 1 diabetes. Lancet. Oct 05 2019; 394(10205): 1274-1285.
51. Walsh RM, Saavedra JR, Lentz G, et al. Improved quality of life following total pancreatectomy and auto-islet transplantation for chronic pancreatitis. J Gastrointest Surg. Aug 2012; 16(8): 1469-77.
52. Webb Ma, Illouz SC, Pollard CA et al. Islet auto transplantation following total pancreatectomy: a long-term assessment of graft function. Pancreas 2008; 37(3):282-287.
53. Wilson GC, Sutton JM, Abbott DE, et al. Long-term outcomes after total pancreatectomy and islet cell autotransplantation: is it a durable operation? Ann Surg. Oct 2014; 260(4):659-665; discussion 665-657.
54. Wilson GC, Sutton JM, Smith MT, et al. Completion pancreatectomy and islet cell autotransplantation as salvage therapy for patients failing previous operative interventions for chronic pancreatitis. Surgery. Oct 2015; 158(4): 872-8; discussion 879-80.
55. Wu Q, Zhang M, Qin Y, et al. Systematic review and meta-analysis of islet autotransplantation after total pancreatectomy in chronic pancreatitis patients [Review]. Endocr J. Mar 30 2015; 62(3):227-234.
56. Zhang YJ, Duan DD, Yuan H. Efficacy and safety of islet autotransplantation after total pancreatectomy in chronic pancreatitis: A systematic review and meta-analysis including 17 studies. Clin Res Hepatol Gastroenterol. Sep 2020; 44(4): 598-608.

POLICY HISTORY:

Medical Policy Group, February 2007 (3)

Medical Policy Administration Committee, February 2007

Available for comment March 1-April 14, 2007

Medical Policy Group, January 2009 (1)

Medical Policy Panel, June 2010

Medical Policy Group, June 2010 (2)

Medical Policy Group, June 2011 (1): Update to Description, Key Points and References

Medical Policy Group, December 2011 (1): 2012 Coding Updates; deleted 0141T, 0142T, 0143T and replaced all with unlisted code 48999

Medical Policy Group, June 2012 (3): 2012 Updates – Key Points & References

Medical Policy Panel, June 2013

Medical Policy Group, June 2013 (3):  2013 Updates to Description, Key Points and References; no change in policy statement

Medical Policy Group, October 2013 (3): Removed ICD-9 Procedure codes; no change to policy statement.

Medical Policy Panel, May 2014

Medical Policy Group, June 2014 (3): 2014 Updates to Description, Key Points & References; added clarification to policy statement “Islet transplantation in all other situations is considered not medically necessary and investigational” – no change in content.

Medical Policy Panel, May 2015

Medical Policy Group, June 2015 (2): 2015 Updates to Key Points and References; no change to policy statement.

Medical Policy Panel, August 2017

Medical Policy Group, September 2017 (7): Updates to Key Points, Approved by Governing Bodies and References. Removed “Previous Coding” section- codes (deleted effective January 1, 2012) 0141T, 0142T, 0143T. No change in Policy Statement.

Medical Policy Panel, August 2018

Medical Policy Group, August 2018 (3): Updates to Description, Key Points and References; No change to policy statement.

Medical Policy Panel, August 2019

Medical Policy Group, September 2019 (3): 2019 Updates to Description, Key Points, and Practice Guidelines and Position Statements. No changes to policy statement or intent.

Medical Policy Group, November 2019:  2020 Annual Coding Update.  Added CPT codes 0584T, 0585T, and 0586T to the Current Coding section.

Medical Policy Panel, August 2020

Medical Policy Group, September 2020 (3): 2020 Updates to Description, Key Points, Practice Guidelines and Position Statements, and References. No changes to policy statement or intent.

Medical Policy Panel, August 2021

Medical Policy Group, August 2021 (3): 2021 Updates to Key Points, Practice Guidelines and Position Statements and References. Policy statement updated to remove “not medically necessary”, no other changes to policy statement.

Medical Policy Panel, August 2022

Medical Policy Group, September 2022 (3): 2022 Updates to Key Points, Practice Guidelines and Position Statements, Approved By Governing Bodies, and References. No changes to policy statement or intent.

Medical Policy Panel, September 2023

Medical Policy Group, September 2023 (3): 2023 Updates to Key Points, Practice Guidelines and Position Statements, Benefit Applications, and References. No changes to policy statement or intent.

Medical Policy Panel, September 2024

Medical Policy Group, September 2024 (3): Updates to Description, Keyp Points, and References. No changes to policy statement or intent.

This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

3. The technology must improve the net health outcome;

4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.

Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and

4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.