CurrentBlue Cross Blue Shield - Rhode IslandPolicy N/A

Immune cell function assays for transplant monitoring

This policy governs coverage determinations for laboratory immune cell function assays (eg, ImmuKnow, Pleximmune) used to monitor or predict immune function in solid organ and hematopoietic stem-cell transplant recipients for Blue Cross Blue Shield - Rhode Island members.

Policy Summary

PayerBlue Cross Blue Shield - Rhode Island

PolicyImmune cell function assays for transplant monitoring

Policy CodePolicy N/A

Change TypeNo material change

Effective DateJan 10, 2015

Next Review DateN/A

Key ActionDo not submit claims for immune cell function assays (CPT 86352, 81560) for Medicare Advantage members; for Commercial members these tests are considered not medically necessary.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

Not coveredMedicare Advantage stance

Not medically necessaryCommercial stance

86352, 81560Not covered codes

InsufficientEvidence conclusion

FDA cleared/approvedRegulatory status

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Coverage Determinations

General coverage

Coverage determination

Overall coverage stance: Use of immune cell function assays to monitor and predict immune function after solid organ transplantation, hematopoietic stem-cell transplantation, and all other indications is not covered for Medicare Advantage plans and considered not medically necessary for Commercial products because the evidence is insufficient to determine effects on health outcomes.

Supported by regulatory summaries and evidence review for ImmuKnow and Pleximmune in the policy.

The following services are explicitly listed as not covered or not medically necessary: CPT 86352 — Cellular function assay involving stimulation (eg, mitogen or antigen) and detection of biomarker (eg, ATP); and CPT 81560 — Transplantation medicine (allograft rejection, pediatric liver and small bowel), measurement of donor and third party-induced CD154+ T‑cytotoxic memory cells, utilizing whole peripheral blood, algorithm reported as a rejection risk score (Effective 1/1/2022).

For Commercial Products, use of immune cell function assays to monitor and predict immune function after solid organ transplantation, hematopoietic stem‑cell transplantation, and all other indications is considered not medically necessary because the evidence is insufficient to determine the effects of the technology on health outcomes.

Coding and Billing

Not Covered / Not Medically NecessaryCPTNot Covered

86352

Cellular function assay involving stimulation (eg, mitogen or antigen) and detection of biomarker (eg, ATP)

Not Covered / Not Medically Necessary (Effective 1/1/2022)CPTNot Covered

81560

Transplantation medicine (allograft rejection, pediatric liver and small bowel), measurement of donor and third party-induced cd154+t-cytotoxic memory cells, utilizing whole peripheral blood, algorithm reported as a rejection risk score (Effective 1/1/2022)

Provider Responsibilities & Billing Impact

Prior Authorization

No prior authorization is applicable for these tests per the policy.

Note

Benefit Verification

Benefits and eligibility are determined by the member's subscriber agreement, Evidence of Coverage, or employer agreement and may vary by contract. For member-specific benefits and eligibility, providers must contact the provider call center.

Denial Risk

Member Responsibility & Denial Risk

Providers should confirm member responsibility before providing services. If a service is determined to be not medically necessary or is a non-covered benefit, the provider may not bill the member unless the member was informed in advance and agreed in writing to accept financial responsibility.

Background and Rationale

Monitoring immunosuppression after solid organ or hematopoietic cell transplantation requires balancing the competing risks of allograft rejection and infection. Therapeutic drug levels do not fully capture overall immune responsiveness, so assays that measure cellular immune function (for example, ATP production in stimulated CD4+ cells or donor‑induced CD154 expression with an Immunoreactivity Index) have been proposed to individualize immunosuppression. However, regulatory clearance or approval (eg, ImmuKnow 510(k); Pleximmune HDE) does not by itself establish clinical utility, and the policy finds the published evidence insufficient and inconsistent to demonstrate improved health outcomes from routine use of these immune function assays for transplant monitoring.

Test Definitions and Terms

ImmuKnow — assay description

Test nameImmuKnow (Cylex) cellular immune function assay

What it measuresIntracellular adenosine triphosphate (ATP) concentration in immunoselected CD4+ T lymphocytes after mitogenic stimulation (15–18 hour incubation with phytohemagglutinin)

Method summaryCD4+ cells are immunoselected, lysed to release intracellular ATP, and luminescence produced from ATP is measured by a luminometer proportional to ATP concentration.

InterpretationATP concentration is compared with fixed ATP production ranges to characterize cellular immune response.

Clinical contextProposed for monitoring immunosuppression to help manage risk of infection and rejection after solid organ or hematopoietic cell transplantation.

Pleximmune / Immunoreactivity Index (IR)

Evidence and Evaluation Context

Note

Test evaluation context and evidence summary

Evaluation context: assays are described for pretransplant and posttransplant use to assess rejection and infection risk, and Pleximmune has FDA HDE approval for predicting rejection within 60 days in pediatric liver and small bowel patients, but the policy concludes evidence is insufficient to support coverage.

ImmuKnow and Pleximmune are described as assays measuring immune response (ATP production for ImmuKnow; CD154/IR for Pleximmune).
Clinical utility is judged insufficient in the policy despite available regulatory clearances/approvals.

Post-Transplant Testing Context

Immune cell function assay testing — Pleximmune regulatory & policy context

FDA statusPleximmune has an FDA Humanitarian Device Exemption (HDE) approval for predicting rejection within 60 days in pediatric liver and small bowel patients.

Policy conclusionDespite the HDE, the policy finds evidence insufficient to support broader clinical utility or coverage for other transplant populations or indications.

Evidence summaryRegulatory documents and small studies show correlation with rejection and survival but are limited by small sample sizes and uncertain clinical validity; no direct clinical‑utility studies identified.

Coverage stance implicationPleximmune’s HDE status does not change the overall policy determination that immune cell function assays are not covered/not medically necessary for general transplant monitoring.

Policy Summary

PayerBlue Cross Blue Shield - Rhode Island

PolicyImmune cell function assays for transplant monitoring

Policy CodePolicy N/A

Change TypeNo material change

Effective DateJan 10, 2015

Next Review DateN/A

Key ActionDo not submit claims for immune cell function assays (CPT 86352, 81560) for Medicare Advantage members; for Commercial members these tests are considered not medically necessary.

SourceLink

On This Page

Step Therapy

No step therapy requirements are specified in this policy.

Billing Rule

Denial Triggers / Billing Impact

Claims for immune cell function assays (e.g., CPT 86352; CPT 81560 for the Pleximmune algorithm) are not covered for Medicare Advantage Plans and are considered not medically necessary for Commercial products; such claims may be denied.

CPT 86352 — Cellular function assay involving stimulation and detection of biomarker (eg, ATP)
CPT 81560 — Transplantation medicine (allograft rejection...), algorithm reported as a rejection risk score (Effective 1/1/2022)

Test namePleximmune (Immunoreactivity Index, IR)

What it measuresDonor-induced CD154 expression on T‑cytotoxic memory cells reported as an Immunoreactivity Index (IR)

IR thresholdsPosttransplant: IR > 1.1 indicates increased rejection risk; Pretransplant: IR threshold = 1.23.

Method summaryPatient peripheral blood lymphocytes are cultured with donor and third‑party cells; cells expressing CD154 are identified by fluorochrome‑stained antibodies and the donor/third‑party response ratio is calculated as the IR.

Regulatory notePleximmune has limited FDA approval documented in regulatory materials; clinical validity conclusions are uncertain due to limited evidence.

Immune function assay / ImmuKnow — general definition

DefinitionImmune function assays measure cell‑mediated immunity, commonly by quantifying ATP production in activated lymphocytes (example: Cylex ImmuKnow).

PurposeIntended to assess overall immune responsiveness to guide management of immunosuppression and estimate risk of infection or rejection in transplant recipients.

Typical methodologyAssays stimulate lymphocytes (eg, with mitogen or donor/third‑party cells), measure a biomarker of activation (eg, intracellular ATP, CD154 expression), and report results against thresholds or ranges.

LimitationsEvidence for clinical utility is limited and inconsistent; tests are proposed adjuncts rather than established standards of care.