CurrentCignaPolicy 0561

Thymus Tissue Transplantation (Rethymic) Coverage Policy

Coverage policy for a single administration of cultured thymus tissue (thymus tissue transplantation, e.g., Rethymic) for pediatric patients with congenital athymia; describes medical necessity criteria, coding guidance, and supporting clinical background.

Policy Summary

PayerCigna

PolicyThymus Tissue Transplantation (Rethymic) Coverage Policy

Policy CodePolicy 0561

Change TypeAnnual review — no clinical policy statement changes

Effective DateAug 15, 2025

Next Review DateAug 15, 2026

Key ActionA single administration of thymus tissue transplantation is covered when policy criteria are met; bill using the listed unlisted CPT/HCPCS and diagnosis codes as applicable.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

singleallowed treatment frequency when medically necessary

≤17patient age limited to pediatrics

<50/mm3T-cell threshold used in eligibility

105clinical evidence base (patients treated)

FDA BLAregulatory status

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

Coverage Criteria — Thymus Tissue Transplantation

Initial therapy — single administration

Covered when ALL of the following are met:

Eligibility for single administration of thymus tissue transplantation: 1) Pediatric individual (age 17 and under). 2) Diagnosis of congenital athymia, including complete DiGeorge anomaly (cDGA) or FOXN1 deficiency. 3) T-cell count lower than 50/mm3 OR naive T-cell (CD3+CD4+CD45RA+CD62L+ or CD3+CD8+CD45RA+CD62L+) count lower than 50/mm3 (study protocols required two separate flow cytometry analyses: one within 3 months and one within 1 month before administration). 4) Absence of genetic defects associated with severe combined immunodeficiency (SCID).naive T-cell (CD3+CD4+CD45RA+CD62L+ or CD3+CD8+CD45RA+CD62L+) count < 50/mm3 (or circulating CD3+CD45RA+CD62L+ < 50/mm3 on two separate analyses)

Patients enrolled under expanded access protocols could have naive T-cell counts >50/mm3 per study descriptions.

Not medically necessary

Not covered indications: Thymus tissue transplantation is considered not medically necessary for all other indications, including but not limited to immune reconstitution in individuals with severe combined immunodeficiency (SCID).

Use of thymus tissue transplantation for indications other than pediatric congenital athymia is explicitly not medically necessary. This includes, but is not limited to, use for immune reconstitution in individuals with severe combined immunodeficiency (SCID).

Annual review notes for this policy indicate No clinical policy statement changes for the listed review dates (including 08/15/2024 and 08/15/2025), and therefore no new clinical policy statement changes were made during those reviews.

Thymus tissue transplantation is considered not medically necessary for all indications other than the specified pediatric congenital athymia criteria. Specifically, use for conditions such as severe combined immunodeficiency (SCID) is not covered under this policy.

Coding and Diagnostic Criteria

Considered Medically Necessary when criteria met (codes listed)mixed

27599	Unlisted procedure, femur or knee
60699	Unlisted procedure, endocrine system
C9399	Unclassified drugs or biologicals
J3490	Unclassified drugs
J3590	Unclassified biologics
D82.1	Di George's syndrome
Q89.2	Congenital malformations of other endocrine glands

Naive T-cell count threshold — numeric threshold and definition of cell subsets

Threshold valueNaive T-cell count < 50/mm3

Cell subset definitionsCD3+CD4+CD45RA+CD62L+ or CD3+CD8+CD45RA+CD62L+ naive T cells

Alternative measurementCirculating CD3+CD45RA+CD62L+ < 50/mm3 on two separate flow cytometry analyses (one within 3 months and one within 1 month before administration)

Study inclusion noteExpanded access protocols allowed some patients to have naive T-cell counts >50/mm3

Provider Actions, Billing & Authorization

Prior Authorization

Prior authorization: None specified for thymus tissue transplantation under this policy.

Denial Risk

Claims & Coding Requirements

Claims for services that are not accompanied by a covered diagnosis or appropriate procedure code will be denied as not covered. Ensure claims include a covered diagnosis (e.g., D82.1, Q89.2) and appropriate procedure coding or unlisted procedure codes as applicable.

Covered diagnosis examples: D82.1 (Di George's syndrome); Q89.2 (Congenital malformations of other endocrine glands)
Procedure coding: 27599 (Unlisted procedure, femur or knee); 60699 (Unlisted procedure, endocrine system)
Drug/biologic coding: C9399, J3490, J3590

Clinical Background

Congenital athymia is a rare, life‑threatening condition characterized by absence of a functioning thymus that results in profound T‑cell deficiency. Affected infants typically present with very low circulating T‑cell and naive T‑cell counts and are at high risk of severe infections and early mortality without immune reconstitution.

Key Definitions

Congenital athymia — definition and related conditions

DefinitionAbsence of a functioning thymus causing profound T-cell immunodeficiency; associated with complete DiGeorge anomaly (cDGA) and other genetic defects

Associated genetic causes22q11.2 deletion (DiGeorge syndrome), FOXN1 deficiency, PAX1 and others

Clinical consequencesProfound T-cell deficiency with high early mortality without intervention; may include conotruncal cardiac anomalies and hypocalcemia

Rethymic (cultured thymus tissue, CTT) — product definition and FDA status

Product descriptionHuman allogeneic processed and cultured postnatal thymus tissue (cultured thymus tissue, CTT; thymus tissue-agdc) implanted into the recipient to reconstitute thymic function

Administration

Revision History & References

2025-08-15Annual reviewLatest

Annual review completed; no clinical policy statement changes noted.

2024-08-15Annual review

Annual review completed; no clinical policy statement changes noted.

References: 13 sources total, including regulatory and clinical literature. Key citations include the FDA Biologics License Application approval documentation: FDA BLA STN BL 125685/0 (BLA approval, October 8, 2021) and related FDA and manufacturer materials listed in the reference section.

Policy Summary

PayerCigna

PolicyThymus Tissue Transplantation (Rethymic) Coverage Policy

Policy CodePolicy 0561

Change TypeAnnual review — no clinical policy statement changes

Effective DateAug 15, 2025

Next Review DateAug 15, 2026

Key ActionA single administration of thymus tissue transplantation is covered when policy criteria are met; bill using the listed unlisted CPT/HCPCS and diagnosis codes as applicable.

SourceLink

On This Page

Billing Rule

Billing Guidance

Billing guidance: Coverage requires meeting the policy clinical criteria and appropriate coding. When using unlisted procedure or drug/biologic codes, include detailed operative notes, pathology, and product information to support medical necessity and facilitate correct reimbursement.

When billing unlisted CPT codes (27599, 60699), include full operative report and rationale for unlisted code use
When billing unclassified drug/biologic codes (C9399, J3490, J3590), include manufacturer/product identification (RETHYMIC) and FDA documentation

Documentation Required

Documentation Requirements

Documentation requirements: Diagnostic testing and clinical documentation must support the diagnosis and eligibility criteria. Include flow cytometry results showing naive T-cell counts on two separate analyses (one within 3 months and one within 1 month prior to administration) unless enrolled under expanded access; genetic testing to document absence of SCID-associated defects; and surgical/anesthesia clearance when applicable.

Two separate flow cytometry analyses demonstrating CD3+CD45RA+CD62L+ (or equivalent naive T-cell subset) count <50/mm3 or <5% of total T cells (one within 3 months, one within 1 month before administration)
Genetic testing or documentation excluding SCID-associated defects
Operative/surgical candidacy documentation if procedure performed

Note

References & Supportive Materials

References: Include applicable regulatory and manufacturer materials with the clinical record when relevant. Key references include the FDA Biologics License Application (BLA) approval documentation and manufacturer information for RETHYMIC.

Note

Clinical Selection & Exclusions

Candidate selection considerations and exclusions from trial/registry: Follow clinical selection notes from the literature—congenital athymia (including complete DiGeorge anomaly or FOXN1 deficiency), required low T-cell/naive T-cell counts, and exclusion of SCID-associated genetic defects. Exclusions include recent or planned major cardiac surgery within 4 weeks prior to administration or within 3 months after, poor surgical candidacy, HIV infection, prior attempts at immune reconstitution (e.g., HSCT), ventilator dependence, and active CMV infection for patients requiring immunosuppression.

Step Therapy

No step therapy requirements or sequencing are specified in this policy.

Note

Policy Review

Annual review note: No clinical policy statement changes were made in the most recent annual reviews (08/15/2024 and 08/15/2025).

Surgical implant of cultured thymus tissue slices into quadriceps muscle pockets; dosing customized by tissue surface area and patient body surface area

FDA statusFDA Biologics License Application (BLA) approved (RETHYMIC) on 10/08/2021

Congenital athymia / DiGeorge syndrome — link to immunodeficiency cause

Link to immunodeficiency causeCongenital athymia can occur as complete DiGeorge anomaly (cDGA) often related to 22q11.2 deletion and leads to absence of thymic tissue and profound T-cell immunodeficiency

Protocol definitionsClinical study protocols defined congenital athymia as cDGA with athymia plus congenital heart defect or hypocalcemia/hypoparathyroidism, or FOXN1 deficiency

Overlap with SCIDComplete DGS (cDGA) may be a form of severe combined immunodeficiency (SCID); exclusion of genetic defects associated with SCID is required for CTT eligibility

RETHYMIC — trade name and one-time therapy note

Trade nameRETHYMIC

Regulatory characterizationOne-time regenerative tissue-based therapy (allogeneic processed thymus tissue-agdc) approved by the FDA for pediatric congenital athymia (BLA STN BL 125685/0)

Dosing/administration noteAdministered as a single administration of cultured thymus tissue slices implanted surgically; dosing customized by tissue surface area and patient body surface area