CurrentBlue Cross Blue Shield - IowaPolicy 07.03.01

Pancreatic Islet Cell Transplant

Covers autologous and allogeneic pancreatic islet cell transplantation policy statements for members of the plan, focusing on use as adjunct to pancreatectomy for chronic pancreatitis and investigational indications including type 1 diabetes.

Policy Summary

PayerBlue Cross Blue Shield - Iowa

PolicyPancreatic Islet Cell Transplant

Policy CodePolicy 07.03.01

Change TypeNo material change

Effective DateOct 1, 2014

Next Review Date

Key ActionVerify member benefits and submit prior authorization documentation including indication, OPTN listing status, and baseline HbA1c/insulin status as applicable.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

autologous coveredAutologous coverage

allogeneic investigationalAllogeneic status

Sep 2025Evidence update

2 listedRelated policies

33%1‑yr insulin independence

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Coverage Criteria for Pancreatic Islet Cell Transplantation

inv-01: Autologous pancreas islet transplantation - Medical necessity

Covered when ALL of the following are met

Autologous islet transplant for chronic pancreatitis undergoing pancreatectomy: Autologous pancreas islet cell transplantation is considered medically necessary as an adjunct to a total or near-total pancreatectomy in individuals with chronic pancreatitis.

Performed to decrease incidence of post‑pancreatectomy diabetes; evidence sufficient for meaningful improvement in net health outcomes.

inv-02: Allogeneic pancreas islet transplantation - Investigational

Not covered / investigational

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

Evidence insufficient to determine improvement in net health outcomes; RCTs and prospective studies show mixed and limited durability.

inv-03: General coverage rationale

Coverage context and clinical rationale

IAT coverage context: Autologous islet transplantation is performed as an adjunct to total or near‑total pancreatectomies for chronic pancreatitis and reduces incidence of diabetes after pancreatectomy; evidence primarily from nonrandomized studies and systematic reviews supports effectiveness in selected patients.

Evidence summarized in systematic reviews and cohort studies; insulin‑independence rates vary and mortality is low but nonzero.

inv-04: Medical necessity criteria for islet transplantation

Covered when ALL of the following are met (evidence-based indications reflected in trials and registries):

Indications and patient selection

Autologous use: Autologous islet transplantation as adjunct to total or near-total pancreatectomy for chronic pancreatitis to reduce post-pancreatectomy diabetes
Supported by nonrandomized studies and systematic reviews

Outcome measurement and follow-up: Document baseline and follow-up HbA1c, severe hypoglycemia events, and stimulated C-peptide; primary endpoints assessed at 12 months after final infusion; short-term (30 day) follow-up for transplant complications and lifelong monitoring for immunosuppression.12 months primary endpoint

Per FDA guidance and trial protocols

Center capability: Procedure must be performed in a hospital setting with specialized staff and capability for islet isolation, infusion, and post-transplant care

inv-05: Coverage-relevant clinical criteria

Coverage considerations and clinical indications referenced in evidence and guidelines

Autologous transplant indication: Autologous islet transplantation is considered in patients undergoing total pancreatectomy for chronic pancreatitis to prevent postsurgical diabetes and improve glycemic outcomes; guideline statements support consideration of this approach.

Supported by ADA 2025 and International Consensus Guidelines 2020

Allogeneic transplant restrictive scenarios

Context: Reserved for patients undergoing renal transplantation or experiencing recurrent ketoacidosis with severe hypoglycemia despite intensive management.
See ADA guidance

OPTN listing criteria: OPTN allows active registration for islet candidates who are insulin dependent or have HbA1c > 6.5%; candidates not meeting those criteria must be inactive until they do.HbA1c > 6.5% or insulin dependent

Allogeneic pancreas islet cell transplantation is considered investigational for all indications, including the treatment of type 1 diabetes. Claims for allogeneic islet transplantation may be denied on this basis; see the related Lantidra policy for review of allogeneic islet cellular therapy products.

Methodology for study selection excluded studies with duplicative or overlapping populations; comparative controlled prospective trials were preferred and single-arm studies were used to assess long-term outcomes when necessary.

The evidence base for allogeneic islet transplantation is limited by generally low to very low quality studies, small sample sizes, few transplant centers, short follow-up, and inconsistent outcome reporting, which constrain conclusions about long-term durability and net health outcomes.

Systematic reviews and health technology assessments note increased adverse events with islet transplantation compared with intensive insulin therapy and call for additional long-term comparative studies to better understand persistence of graft function and the effects of immunosuppression.

The International Consensus Guidelines for Chronic Pancreatitis list contraindications to pancreatectomy with islet transplant including active alcoholism, pancreatic cancer, end-stage systemic illness, and psychiatric or socioeconomic barriers that would impede the procedure or posttransplant care.

Reiterating the policy stance: allogeneic islet cell transplantation is considered investigational (not medically necessary) for type 1 diabetes and for other indications outside the autologous post-pancreatectomy setting due to insufficient evidence of net health benefit.

There is concern about procedures performed outside specialized centers or without adequate follow-up and outcome reporting; many published series are single-center and adequate long-term data are critical to assess durability and safety.

NICE guidance noted that allogeneic pancreatic islet cell transplantation is associated with serious procedure-related complications and that long-term immunosuppression carries substantial risks; autologous reports showed short-term efficacy with many patients requiring insulin long term and most complications related to the pancreatectomy.

Coding and Administrative Identifiers

Codes table referencedmixed

No codes listed

Procedure 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 / Medicare 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.

inv-16: Literature search cutoff

Literature search cutoffMost recent literature update performed through September 2025.

Initial evidence review createdEvidence review originally created in October 2014.

Search databasePubMed database searches used for updates.

inv-17: Primary endpoint timing — Measured at 12 months after final infusion

Primary endpoint timingPrimary end points should be measured at 12 months after the final infusion.

Short-term follow-upShort-term (30 day) follow-up required to monitor transplant-related complications.

Long-term follow-upLong-term follow-up (1–3, 5, or 10 years) required to assess durability of glucose control.

inv-18: OPTN active listing HbA1c threshold — > 6.5% HbA1c

OPTN active listing HbA1c threshold> 6.5% HbA1c is required for active registration (or insulin dependence).

Active status documentation windowUse the most recent HbA1c test performed within the last 6 months to determine active status.

Reporting requirementChanges in candidate status must be reported to OPTN within 72 hours of knowledge.

Provider Actions, Prior Authorization, and Documentation

Billing Rule

Prior Authorization and Coding Note

Prior authorization is not applicable for this policy section. Providers must use the Codes table when submitting claims to ensure correct CPT/HCPCS and diagnosis coding for islet transplantation and related pancreatectomy procedures.

Verify member benefits and contract exclusions before authorization determinations.
Use listed CPT/HCPCS codes or appropriate unlisted procedure code (e.g., 48999) with supporting documentation when coding islet transplantation services.

Prior Authorization

Prior Authorization for Islet Transplantation

Allogeneic islet transplantation is considered investigational for all indications; claims for allogeneic (donor-derived) islet procedures may be denied. Prior authorization for autologous islet transplantation should confirm the indication and planned islet dosing/infusion strategy when applicable.

Allogeneic/transplantable tissue products (e.g., Lantidra/donislecel) are reviewed under separate drug/device policies.
For autologous procedures, prior authorization should document intended islet equivalents per kg and number/timing of infusions when available.

Note

Study Selection — Duplication and Overlap

Studies with duplicative or overlapping populations were excluded during evidence selection to avoid double-counting outcomes and bias in effectiveness assessments. This exclusion criterion applies to registry analyses and single-arm studies where patient cohorts overlap across reports.

When submitting evidence or peer-reviewed publications for medical necessity review, indicate whether study cohorts overlap with other cited studies.

Documentation Required

Follow-up and Outcome Documentation

Short-term (30 day) follow-up is required to monitor for transplant-related complications. Primary endpoints should be measured at 12 months after the final infusion to assess durability. Long-term follow-up (1–3, 5, and up to 10 years) — and lifelong monitoring for immunosuppression-related issues in allogeneic cases — is expected to document outcomes such as insulin independence, HbA1c, severe hypoglycemia events, and stimulated C-peptide.

Document baseline and follow-up HbA1c (most recent within 6 months for OPTN active listing), insulin use/status, episodes of severe hypoglycemia, and stimulated C‑peptide results.
Primary efficacy outcomes should be reported at 12 months post-final infusion; additional reporting at 1–3, 5, and 10 years is recommended when available.

Documentation Required

OPTN Listing Requirements for Islet Candidates

OPTN allocation and listing rules require that a transplant hospital may list an islet candidate as active only if the candidate is insulin dependent or has HbA1c > 6.5%. If a candidate does not meet these criteria, the hospital must list the candidate as inactive. Changes in candidate status must be reported and documented per OPTN timelines.

If activating an inactive candidate, document which criterion (insulin dependence or HbA1c > 6.5%) is met.
Report any change from active to inactive status to the OPTN within 72 hours of the transplant hospital's knowledge and document the timing in the medical record.
When determining active status, use the most recent HbA1c test performed within the last 6 months.

Documentation Required

OPTN Documentation and Reporting

For OPTN reporting when a candidate is active and insulin independent, the transplant hospital must document the candidate’s insulin status and most recent HbA1c (within 6 months) in the medical record.

Maintain documentation of insulin independence and HbA1c in the candidate’s chart for audit and reporting purposes.
Ensure HbA1c values used for active status determination are from tests performed within the prior 6 months.

Step Therapy

No formal step therapy requirements are specified in this policy. For type 1 diabetes, transplantation is generally reserved for high-risk patients (for example, those undergoing renal transplantation or with recurrent ketoacidosis and severe hypoglycemia despite intensive management).

Document prior intensive medical management in type 1 diabetic candidates when relevant (e.g., intensive insulin therapy, education, and hypoglycemia management interventions).

Note

Conservative Therapy Context and Comparator Requirement

Conservative therapy comparators include medical management for chronic pancreatitis (medications, endoscopy) and intensive medical management for type 1 diabetes (daily insulin, diet, lifestyle). Documentation should show failure or inadequacy of conservative/nonoperative management when relevant to justify surgical/interventional approaches.

For chronic pancreatitis candidates, include prior nonoperative therapies such as endoscopic interventions or optimized medical therapy in the record.
For type 1 diabetes candidates, document prior intensive insulin therapy and measures attempted to manage severe hypoglycemia or glycemic instability.

Prior Authorization

Step Therapy / Prior Treatment Guidance

Transplantation for type 1 diabetes should generally be reserved for specific high-risk groups and after documentation of failure or inadequacy of intensive medical management when applicable. No explicit stepwise prior-treatment sequence is mandated by this policy, but reviewers will consider prior therapies in assessing medical necessity.

When applicable, provide evidence of prior intensive management (insulin regimens, education, hypoglycemia protocols) and justification for transplantation.
For chronic pancreatitis with planned autologous islet transplant, document indication (e.g., severe/refractory pain, total/near-total pancreatectomy planned) and prior conservative management.

Candidate Selection Criteria

inv-43: Autologous candidate criteria

Candidate population for autologous procedure

Candidate criteria: Individuals with chronic pancreatitis undergoing total or near-total pancreatectomy for intractable pain who are at risk of becoming insulin-dependent post-pancreatectomy.

Primary risk factors categorized by TIGAR-O; procedure intended to reduce incidence of diabetes after pancreatectomy.

inv-44: Candidates

Patient population for candidate consideration

Candidate selection: Individuals with chronic pancreatitis undergoing total or near‑total pancreatectomy; typically those with painful, treatment‑refractory disease where pancreatectomy is planned.

Evidence demonstrates pain control benefits in ~2/3 of selected patients; insulin‑independence rates are modest and decline over time.

inv-45: Islet transplant candidate criteria

Candidate selection reflected in trials and consortium protocols:

Primary candidate criteria: Adults with type 1 diabetes experiencing severe hypoglycemia or hypoglycemia unawareness or metabolically unstable diabetes despite optimal medical therapy; some protocols included patients post-kidney transplantage 18-65 in TRIMECO trial

TRIMECO RCT and CIT protocols

inv-46: Islet candidate active status criteria

OPTN allocation/listing criteria for islet candidates

Active listing criteria: Candidate must be insulin dependent OR have HbA1c > 6.5% to be listed as active.HbA1c > 6.5%

OPTN allocation policy (2022) requires documentation of insulin status and most recent HbA1c within 6 months for active listing.

Contraindications and Procedural Risks

This section does not list specific absolute or relative contraindications within the policy text; however, readers should recognize the significant risks associated with maintenance immunosuppression and surgical complications when considering islet transplantation.

Surgical complication rates and short-term mortality are reported in the literature and should be considered alongside immunosuppression‑related risks such as renal function decline and infectious complications.

The document does not enumerate explicit absolute contraindications here, but notes procedural risks including surgical complications and nonzero short‑term mortality (reported 30‑day mortality estimates in systematic reviews and series), which should inform clinical decision making and candidate selection.

Again, no specific absolute or relative contraindications are listed in this portion of the policy; nevertheless, providers must weigh the risks of immunosuppression and procedure‑related harms given the limited and variable quality of evidence for many indications.

No additional specific absolute or relative contraindications are provided in this section of the policy; refer to guideline statements (e.g., International Consensus Guidelines) for recommended exclusions such as active alcoholism, pancreatic malignancy, or conditions that would impair postoperative care.

Post-Transplant Coverage and Follow-Up

inv-62: Autologous islet cell isolation and portal vein infusion at time of pancreatectomy — Considered part of surgical management rather than separate long-term coverage

Procedure contextIsolation of autologous islets and infusion into the portal vein is performed during the pancreatectomy procedure as part of surgical care.

Coverage stanceAutologous islet cell isolation and portal vein infusion at time of pancreatectomy are considered part of the operative management rather than a separately billed long-term transplant service.

RationaleProcedure is performed in individuals already undergoing pancreatectomy and is not associated with additional serious complications beyond the index surgery.

inv-63: Clinical follow-up and outcome reporting — Short-term (30 day) and long-term follow-up at intervals up to 1, 3, 5, and 10 years

Follow-up schedule (short-term)30-day follow-up required to monitor for transplant-related complications.

Long-term follow-up intervalsRecommended follow-up intervals include assessments at 1, 3, 5, and 10 years to monitor durability and outcomes.

Outcome reportingDocumentation should include baseline and follow-up measures such as HbA1c, severe hypoglycemia events, and C-peptide to support outcome reporting.

inv-64: Follow-up testing and monitoring — Follow-up visits, HbA1c and C-peptide testing, renal function monitoring, management of immunosuppression adverse effects

Required testingFollow-up visits should include measurement of HbA1c and stimulated C-peptide as part of outcome assessment.

Renal monitoringMonitor renal function (e.g., GFR) because immunosuppression can decrease glomerular filtration rate.

Immunosuppression adverse effectsOngoing management and monitoring for immunosuppression-related adverse events (infections, cytopenias) are required.

inv-65: Long-term monitoring — Follow-up monitoring and management of immunosuppression and graft function; median graft durations and follow-up durations noted

Long-term monitoring necessityLifelong follow-up is recommended to assess durability of glucose control and manage immunosuppression and graft function.

Reported graft durationsMedian graft function durations reported (example: median 4.4 years on immunosuppression in Lemos et al. series).

Follow-up duration in studiesSome series report long median follow-up (e.g., 13.8 years) with survival and graft function outcomes reported up to 20 years.

Background and Definitions

Background: Islet cells may be autologous (harvested from the patient’s own resected pancreas) or allogeneic (from a deceased donor). Autologous islet transplantation is typically performed at the time of total or near‑total pancreatectomy to preserve β-cell function and reduce the likelihood of insulin‑dependent diabetes after surgery.

inv-36: Definition — Autologous islet transplantation: isolation from patient's resected pancreas and infusion into portal vein

Definition (autologous IAT)Autologous islet transplantation: islet cells are isolated from the patient's resected pancreas using enzymes and the cell suspension is injected into the recipient's portal vein during pancreatectomy.

PurposePerformed to preserve beta-cell insulin production and reduce incidence of post-pancreatectomy diabetes.

Typical settingProcedure is performed at the time of total or near‑total pancreatectomy and the implanted islets engraft in the liver.

inv-37: Definition — Allogeneic islet transplantation: donor islets from deceased donor, experimental for type 1 diabetes

Definition (allogeneic)Allogeneic islet transplantation: islets are harvested from a deceased donor's pancreas, processed, and injected into the recipient's portal vein; typically requires maintenance immunosuppression.

Clinical contextInvestigational for treatment of type 1 diabetes due to variable outcomes and need for long‑term immunosuppression.

Procedure locationAllogeneic transplantation may be performed in settings such as the radiology department for percutaneous infusion.

inv-38: Definition — Autologous islet transplantation (IAT) shorthand

Shorthand termAutologous islet transplantation is commonly abbreviated as IAT when performed at time of pancreatectomy.

Use caseIAT is used as an adjunct to total or near‑total pancreatectomy for chronic pancreatitis to reduce post‑surgical diabetes.

Distinct from allogeneicIAT uses the patient's own islets and therefore does not require maintenance immunosuppression.

inv-39: Definition — Insulin independence outcome definition and variability across studies

Insulin independence outcomeInsulin independence denotes not requiring exogenous insulin post‑transplant; definitions vary across studies but registry reports often use short durations (e.g., ≥2 weeks) or sustained independence at specified follow-up intervals.

Variation in ratesReported insulin‑independence rates vary widely across studies and time points (e.g., 52.1% at 1 year in CIT07; lower rates in longer follow-up cohorts).

Related endpointsOther key metabolic endpoints include attainment of HbA1c ≤7% and elimination of severe hypoglycemia.

inv-40: Definition — Metabolically unstable / 'brittle' type 1 diabetes definition

Definition (metabolically unstable)Metabolically unstable or 'brittle' type 1 diabetes refers to individuals with highly labile blood glucose, severe or recurrent hypoglycemia, or hypoglycemia unawareness despite intensive medical therapy.

Endpoints relevanceFDA guidance accepts attainment of normal HbA1c (<6.5%) and elimination of hypoglycemia as acceptable primary end points for these patients.

Candidate considerationAllogeneic islet transplantation trials have focused on this population, but durability and long‑term benefits remain uncertain.

inv-41: Definition repeat — Autologous islet transplantation described

Autologous islet transplantation describedIslet cells are isolated from the patient's resected pancreas and infused into the portal vein during the pancreatectomy to produce insulin post-implantation.

MechanismOnce implanted, beta cells in the islets begin to make and release insulin in the liver environment.

Clinical intentPerformed to preserve beta-cell function and reduce post‑pancreatectomy insulin dependence.

inv-42: Definition repeat — Allogeneic islet transplantation described

Allogeneic islet transplantation describedDonor islets from a deceased donor are processed and injected into the recipient's portal vein; maintenance immunosuppression is typically required.

Research statusAllogeneic transplantation remains investigational for type 1 diabetes due to mixed evidence and immunosuppression risks.

Key protocolThe 'Edmonton protocol' (sirolimus, tacrolimus, daclizumab) is a historically referenced immunosuppression regimen to improve outcomes.

OpenPayer

Pancreatic Islet Cell Transplant

Coverage Criteria for Pancreatic Islet Cell Transplantation

Coding and Administrative Identifiers

Provider Actions, Prior Authorization, and Documentation

Candidate Selection Criteria

Contraindications and Procedural Risks

Evaluation and Outcome Measurement Requirements

Center and Program Requirements

Post-Transplant Coverage and Follow-Up

Background and Definitions

Revision History and Related Policies