CurrentBlue Cross Blue Shield - South DakotaPolicy N/A

Pancreatic Islet Cell Transplant

Defines coverage stance for autologous and allogeneic pancreatic islet cell transplantation for members of Wellmark/Blue Cross Blue Shield - South Dakota; addresses use with total or near-total pancreatectomy for chronic pancreatitis and use in type 1 diabetes.

Policy Summary

PayerBlue Cross Blue Shield - South Dakota

PolicyPancreatic Islet Cell Transplant

Policy CodePolicy N/A

Change TypeNo material clinical or coverage changes

Effective DateOctober 2014

Next Review DateOctober 2025

Key ActionVerify member benefits and document OPTN active listing criteria including insulin status and recent HbA1c; obtain prior authorization where payer rules apply.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

Medically necessaryAutologous stance

InvestigationalAllogeneic stance

2018 RCTRCT cited

33%1‑yr pooled insulin‑independence

Coverage Determinations and Evidence Summary

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Candidate selection and listing criteria

Covered when ALL of the following are met:

ALL of the following

Patient is undergoing total or near-total pancreatectomy for chronic pancreatitis or other benign pancreatic disease (not for pancreatic malignancy).
Per International Consensus, major indications include debilitating pain or recurrent pancreatitis diminishing quality of life.
Autologous (recipient-derived) islet cell transplantation will be performed as an adjunct to the total or near-total pancreatectomy (i.e., islet autotransplantation at the time of pancreatectomy).
There is documentation that the patient has failed or is not a candidate for less invasive therapies aimed at pain control or management of chronic pancreatitis (e.g., endoscopic and operative therapies), and disease is refractory and significantly impairs quality of life.
No contraindications to pancreatectomy with islet transplant are present (examples include active alcoholism, pancreatic cancer, end-stage systemic organ dysfunction, psychiatric illness or socioeconomic factors precluding posttransplant care).
Contraindications per International Consensus.
The procedure is performed at a center with appropriate surgical, islet isolation, and posttransplant care capabilities and documentation of multidisciplinary evaluation and informed consent.

Candidate Selection and Listing Criteria

Candidate selection

Candidate population described

Chronic pancreatitis candidates: Individuals with chronic pancreatitis undergoing total or near‑total pancreatectomy for intractable pain; decision must balance expected pain relief against the certainty of postoperative insulin‑dependent diabetes.

Primary risk factors for chronic pancreatitis (TIGAR‑O) may apply; pain must be intractable and balanced against diabetes risk.

Candidate Criteria

Candidate selection informed by trial populations

Age and indication: Adults (trial ranges generally 18–65) with type 1 diabetes and severe hypoglycemia or unstable glycemic control; may include patients post‑kidney transplant in trial protocols.

Eligibility ranges and indications derived from TRIMECO and CIT protocols.

Prior therapy: Failed or inadequate control with intensive medical therapy (daily insulin, diet, and lifestyle) or continued severe hypoglycemia despite optimized care.

Comparator arms in randomized and single‑arm trials required intensive medical therapy prior to transplantation.

Islet transplant candidate criteria

Criteria drawn from OPTN and professional guidelines where provided in document

Active listing: Candidate is insulin dependent OR has HbA1c > 6.5%.HbA1c >6.5%

OPTN allocation policy for active islet candidate registration; document insulin status and most recent HbA1c within 6 months when applicable.

Reserved indications for allogeneic islet transplant: Allogeneic islet transplantation generally reserved for patients undergoing renal transplantation or those with recurrent ketoacidosis or severe hypoglycemia despite intensive management.

Reflects ADA guidance noting immunosuppression risks and restricted indications.

Procedure and Billing Codes

Codes table referencedmixed

No codes listed

CPT CodesCPT

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).
0584T	Islet cell transplant, includes portal vein catheterization and infusion, including all imaging, including guidance, and radiological supervision and interpretation, when performed; percutaneous.
0585T	Islet cell transplant, includes portal vein catheterization and infusion, including all imaging, including guidance, and radiological supervision and interpretation, when performed; laparoscopic.
0586T	Islet cell transplant, includes portal vein catheterization and infusion, including all imaging, including guidance, and radiological supervision and interpretation, when performed; open.

HCPCS/G-codes and S-codeHCPCS

G0341	Percutaneous islet cell transplant, includes portal vein catheterization and infusion.
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	Transplant, islet cell tissue, allogeneic.

Covered CPT CodesCPT

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).
0584T	Islet cell transplant, includes portal vein catheterization and infusion, including all imaging, including guidance, and radiological supervision and interpretation, when performed; percutaneous.
0585T	Islet cell transplant, includes portal vein catheterization and infusion, including all imaging, including guidance, and radiological supervision and interpretation, when performed; laparoscopic.
0586T	Islet cell transplant, includes portal vein catheterization and infusion, including all imaging, including guidance, and radiological supervision and interpretation, when performed; open.

HCPCS and other codesHCPCS

G0341	Percutaneous islet cell transplant, includes portal vein catheterization and infusion.
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	Transplant, islet cell tissue, allogeneic.

Primary endpoint timing

Primary endpoint timingMeasured at 12 months after the final infusion to assess durability of glycemic control and primary outcomes

Short-term safety window30-day follow-up required to monitor transplant-related complications

Long-term surveillanceLifelong follow-up recommended to monitor durability and immunosuppression effects

Islet dose used in TRIMECO trial

Islet dose (TRIMECO RCT)11,000 islet equivalents per kg body weight delivered in one to three infusions

Infusion scheduleDose could be administered across one to three separate infusions as reported in the trial

Trial population contextUsed in adult patients (aged 18–65) with type 1 diabetes and severe hypoglycemia or poor glycemic control post-kidney transplant

OPTN HbA1c threshold for active listing

OPTN active-listing HbA1c threshold> 6.5% (candidate qualifies as active if insulin dependent OR HbA1c > 6.5%)

Documentation timingMost recent HbA1c must be within the prior 6 months when determining active status

Reporting requirementChanges in candidate active/inactive status must be reported to OPTN within 72 hours of knowledge

Authorization, Documentation, and Operational Guidance

Prior Authorization

Prior Authorization Required

Prior approval is required per payer rules: prior authorization is required for pancreatectomy with autologous islet transplantation and for islet transplant procedures listed below. Verify member benefits and contract exclusions prior to scheduling; benefit determinations depend on the member's contract.

Prior authorization required for listed CPT and HCPCS codes related to islet transplantation and pancreatectomy with autologous islet transplant.
Verify member benefits and contract language; exclusions or limitations may apply.

Documentation Required

Specialized Center and Indication Documentation

Islet transplantation (autologous or allogeneic) is performed in specialized hospital settings with staff and facilities capable of islet cell isolation, processing, and portal vein infusion and to manage peri-procedural and post-transplant care. Documentation should justify that the procedure is being performed in an appropriately equipped center and explain the clinical indication for specialty care.

Document availability of cell isolation and re-infusion capability at the facility.
Document rationale for performing islet transplantation at a specialized center.

Billing Rule

Procedure Coding and Authorization

Report procedures using the specified CPT and HCPCS codes for islet transplantation and pancreatectomy with autologous islet transplant. Use the unlisted pancreatic code only when a specified code is not appropriate; use of unlisted code 48999 instead of the specified CPT/HCPCS codes may increase risk of claim denial.

Covered/Reported CPT codes include 48160 (pancreatectomy with autologous transplantation), 0584T, 0585T, 0586T (islet cell transplant percutaneous/laparoscopic/open) and unlisted 48999 when specified.
HCPCS codes: G0341, G0342, G0343, S2102 (allogeneic islet transplant).
Avoid use of 48999 when a specific CPT/HCPCS code applies; incorrect coding may increase denial risk.

Note

Trial Limitations Affecting Candidate Selection

Clinical trials and studies in this area have limitations that affect candidate selection and evidence interpretation: many trials are open-label, have small sample sizes, short follow-up, or lack randomized controls. These limitations should be considered when assessing candidacy and counseling patients about expected outcomes and durability of benefit.

Randomized trials (e.g., TRIMECO) had limited follow-up and open-label designs.
Single-arm or small studies may not establish long-term durability; primary endpoints often measured at 12 months after final infusion.

Documentation Required

Follow-up and Endpoint Documentation

Follow-up requirements and endpoint documentation must be recorded: short-term follow-up (≈30 days) to monitor transplant-related complications and longer-term follow-up (1–3, 5, and up to 10 years; for allogeneic transplantation, lifelong monitoring for immunosuppression) to assess durability of glucose control, insulin independence, HbA1c, and hypoglycemia outcomes. For protocols using primary endpoints, document timing (e.g., 12 months after final infusion) and relevant measures (HbA1c, insulin use, hypoglycemia events).

Document 30-day post-procedure complication assessment.
Document primary endpoint assessments at 12 months after final infusion (HbA1c, insulin independence, hypoglycemia elimination).
Document longer-term follow-up plans (1–3, 5, 10 years; lifelong for immunosuppressed allogeneic recipients).

Documentation Required

OPTN Reporting and Documentation

OPTN registration and reporting requirements must be documented in the medical record. If registering a candidate as active, document that the candidate meets OPTN active-status criteria (insulin dependence OR HbA1c > 6.5%). If a candidate's status changes, report the change to the OPTN Contractor within 72 hours and document when the transplant program learned of the change. Use the most recent HbA1c within six months when determining active status.

Document insulin dependence or recent HbA1c (>6.5%) to justify active registration.
Report and document any change in candidate active/inactive status to OPTN within 72 hours of awareness.
Record the most recent HbA1c (within 6 months) when assessing active status.

Documentation Required

Conservative and Prior Medical Therapy Precedent

Conservative therapy and prior medical management must be documented before considering pancreatectomy with autologous islet transplant for chronic pancreatitis. Candidates are generally those who have failed intensive medical management (medications, endoscopy) and continue to have poorly controlled pain or complications warranting total/near-total pancreatectomy.

Document prior medical therapies attempted (medications, endoscopic interventions) and failure or inadequate control.
Document that conservative/medical management was optimized prior to referral for surgical pancreatectomy with islet autotransplantation.

Key Definitions

Autologous islet transplantation

DefinitionAutologous islet transplantation: isolation of islet cells from the patient's resected pancreas with infusion into the portal vein of the liver during pancreatectomy

Usual settingPerformed as part of total or near-total pancreatectomy for chronic pancreatitis to preserve endocrine function

RationaleAims to reduce the likelihood of postoperative insulin-dependent diabetes by reimplanting the patient's own beta cells

Allogeneic islet transplantation

DefinitionAllogeneic islet transplantation: islets harvested from a deceased donor pancreas, processed, and injected into the recipient's portal vein to restore insulin production

Clinical contextInvestigated as an alternative to whole-organ pancreas transplant for type 1 diabetes, typically reserved for patients with severe metabolic complications

Special requirementsUsually requires immunosuppression (e.g., protocols such as the Edmonton regimen) and specialized hospital-based cell isolation and infusion capabilities

Autologous pancreas islet transplantation (IAT)

Definition (IAT)Autologous pancreas islet transplantation (IAT): isolation and transplantation of a patient's own pancreatic islet cells at the time of total or near-total pancreatectomy

IndicationPerformed during pancreatectomy to preserve endocrine pancreatic function and reduce postsurgical diabetes risk in chronic pancreatitis patients

Procedure noteIslets are isolated using enzymatic digestion of the resected pancreas and infused into the portal vein of the liver during the same surgical episode

Allogeneic islet transplantation (note)

Definition (repeated)Allogeneic islet transplantation: donor (cadaveric) islets processed and injected into recipient portal vein, often requiring immunosuppression and specialized infusion procedures

Typical candidatesGenerally reserved for individuals with type 1 diabetes who have severe hypoglycemia or unstable glycemic control despite intensive therapy

SettingMay be performed in interventional radiology or hospital-based specialized centers with cell isolation and re-infusion capability

Primary endpoints — Insulin independence and glycemic control

Insulin independenceOutcome indicating the patient no longer requires exogenous insulin posttransplant (reported variably across trials; assessed at prespecified timepoints such as 12 months)

Glycemic control endpointsMeasures include HbA1c targets (e.g., ≤6.5% or ≤7% depending on protocol), reduction/elimination of severe hypoglycemia, and fasting plasma glucose or C-peptide measures

Timing for assessmentPrimary glycemic endpoints commonly assessed at 12 months after final infusion to evaluate durability

Active islet candidate (OPTN)

OPTN active candidate definitionA candidate may be registered as active if they are insulin dependent OR have HbA1c > 6.5%

Inactive statusCandidates not meeting either requirement must be registered as inactive

Documentation requirementIf active and insulin-independent, the hospital must document insulin status and most recent HbA1c (within 6 months) in the medical record

48160 — Pancreatectomy with autologous transplantation

Code 48160Pancreatectomy, total or subtotal, with autologous transplantation of pancreas or pancreatic islet cells

Typical useReported for surgical pancreatectomy procedures that include harvesting and autologous islet transplantation

Coding noteProvider must report appropriate CPT, HCPCS, revenue and ICD diagnosis codes as listed in the policy's code section

0584T-0586T — Category III islet transplant CPT codes

0584TIslet cell transplant, includes portal vein catheterization and infusion; percutaneous (includes imaging and guidance)

0585TIslet cell transplant, includes portal vein catheterization and infusion; laparoscopic

0586TIslet cell transplant, includes portal vein catheterization and infusion; open

Pre-Transplant Evaluation and Follow-up Requirements

Note

Perform standard surgical evaluation vs medical management

Evaluation for autologous IAT should follow standard surgical decision‑making comparing autologous IAT versus medical management for chronic pancreatitis; document the PICO rationale and prior conservative treatments.

Include clinical rationale comparing expected benefits versus standard medical/endoscopic management.

Documentation Required

Require 30‑day and long‑term follow‑up

Short‑term (30 days) and long‑term (1–10 years) follow‑up are required to monitor complications and durability of glucose control after islet transplantation; include follow‑up plan in the medical record.

Plan for 30‑day safety monitoring and longer‑term assessments at intervals such as 1, 3, 5, and up to 10 years.

Documentation Required

Include operational short‑ and long‑term monitoring

Operational monitoring should include both short‑term (30 days) and long‑term (1–10 years) follow‑up to assess complications and durability of glycemic control following transplant.

Documentation Required

Document ongoing follow‑up for outcomes and adverse events

Short‑term (30 days) and long‑term follow‑up are necessary and should be used for ongoing evaluation of outcomes and adverse events after islet transplantation.

Documentation Required

Maintain documented follow‑up for operational monitoring

Short‑term (30 days) and long‑term (1–10 years) follow‑up should be documented and used for operational monitoring of transplant outcomes and durability.

Post-Transplant Monitoring and Outcomes

Allogeneic islet transplantation follow-up — evidence summary

Long-term outcomes unclearLong-term outcomes for allogeneic islet transplantation are unclear; evidence is conflicting regarding reduction of diabetic complications

RCT limitations2018 RCT suggested reduced severe hypoglycemia but had limited follow-up and other limitations reducing certainty

Need for comparative studiesLong-term comparative studies are required to determine effects on net health outcomes

Clinical follow-up and outcome assessment

Required short-term monitoring30-day follow-up required to monitor for transplant-related complications

Longer interval assessmentsFollow-up assessments recommended at 1–3 years, 5 years, and up to 10 years to establish durability of glucose control

Endpoint documentationDocumentation should include intent to assess glycemic targets (e.g., HbA1c goals) with a 12-month assessment plan

Long-term monitoring and management

Short-term follow-up30-day posttransplant monitoring for complications is required

Long-term/lifelong follow-upLifelong follow-up recommended to assess durability of glycemic control and manage immunosuppression-related effects

Periodic outcome reportingOutcome data commonly reported at 1, 2, 3 years and longer; median graft function durations (e.g., 4.4 years) have been observed in series

Clinical follow-up, immunosuppression management

Follow-up outcome timepointsReported outcomes include assessments at 1, 2, and 3 years posttransplant and longer-term registry/case-series follow-up

Median graft function exampleMedian duration of graft function on immunosuppression reported as 4.4 years in a long-term case series

Immunosuppression impactFollow-up must monitor renal function and adverse events related to immunosuppression, which have been observed in multiple trials