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Allogeneic Processed Thymus Tissue-agdc (Rethymic®)


The Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition.


Allogeneic processed thymus tissue-agdc (Rethymic​) is considered medically necessary and, therefore, covered for the treatment of congenital athymia when ALL of the following criteria are met: 
  • The individual is 3 years of age or younger; AND
  • The individual has a diagnosis of congenital athymia confirmed by flow cytometry demonstrating fewer than 50 naïve T-cells/mm3 (CD45RA+, CD62L+) in the peripheral blood or less than 05% of total T-cells being naïve in phenotype; AND
  • The individual has complete DiGeorge syndrome (cDGS) and at least one of the following:

a. Congenital heart defect; OR

b. Hypoparathyroidism or hypocalcemia requiring calcium replacement; OR

c. 22q11.2 deletion syndrome; OR

d. 10p13 hemizygosity; OR​

e. CHARGE (coloboma, heart defects, choanal atresia, growth and development retardation, genital hypoplasia, and ear anomalies including deafness) syndrome; OR

f. clinically-supported & estbalished pathogenic mutation(s)/variation(s) in CHD7, FOXN1, TBX1, TBX2, and/or the PAX1 genes leading to confirmed congenital athymia​; AND

  • The individual is NOT being treated for severe combined immunodeficiency (SCID); AND
  • The individual has been screened for anti-HLA antibodies prior to receiving treatment with the requested agent; AND
  • For individuals who received prior solid organ (e.g., thymus) or hematopoietic cell transplantation, the patient has undergone HLA matching of the requested agent to recipient alleles; AND
  • The requested quantity does NOT exceed the maximum units, (i.e. 22,000) allowed for the duration of approval (i.e. 180 days (one treatment course per lifetime); AND
  • Dosing is administered per the FDA-approval: 5,000 to 22,000 mm2 of Rethymic surface area/m2 recipient body surface area (BSA) administered by surgical procedure.

Allogeneic processed thymus tissue-agdc (Rethymic)  is considered experimental/investigational and, therefore, not covered because their safety and/or effectiveness cannot be established by review of the available published peer-reviewed literature.


The Company may conduct reviews and audits of services to our members regardless of the participation status of the provider. Medical record documentation must be maintained on file to reflect the medical necessity of the care and services provided. These medical records may include but are not limited to: records from the professional provider’s office, hospital, nursing home, home health agencies, therapies, and test reports.



Subject to the terms and conditions of the applicable benefit contract, allogeneic processed thymus tissue-agdc (Rethymic) is covered under the medical benefits of the Company’s products when the medical necessity criteria and the Company applicable precert/preapproval requirements listed in this medical policy are met.

However, services that are identified in this policy as experimental/investigational are not eligible for coverage or reimbursement by the Company.


On October 8, 2021, the U.S. Food and Drug Administration approved Rethymic for the treatment of pediatric indiviuals with congenital athymia. Rethymic is the first thymus tissue product approved in the United States of America. 

Limitations of Use: Allogeneic processed thymus tissue is not indicated for the treatment of individuals with severe combined immunodeficiency (SCID). 

Surgical implantation of Rethymic into the quadriceps muscle should be done by a qualified surgical team in a single surgical session at a qualified hospital. Refer to the product labeling for detailed administration instructions. As of February 2024, in the United States, Duke Children’s Hospital is the only medical center that performs this procedure.

The dosage is determined by the total surface area of the Rethymic slices and the recipient’s body surface area (BSA). A slice is defined as the contents on a single filter membrane (the slices are variable in size and shape). The recommended dose range is 5,000 to 22,000 mm2 of Rethymic surface area per m2 recipient BSA. The manufacturer calculates the dose in advance for the specific patient; the amount of product provided is adjusted at the manufacturing facility to ensure the maximum dose for the patient cannot be exceeded. Up to 42 cultured slices will be provided for each patient. At the time of surgery, the manufacturing personnel communicate to the surgical team the portion of the product that represents the minimum dose.


Following will be confirmed during the Company's applicable precert/preapproval requirements:

1.) The indivual’s congenital athymia diagnosis has been confirmed by and the individual’s treatment plan (including Rethymic implantation) and follow-up care will be under the supervision of a pediatric immunologist or other specialist with expertise in the management of congenital athymia.

2.) The individual is currently receiving, and will continue to receive, standard of care supportive measures for congenital athymia until immune reconstitution is deemed sufficient (generally at least 9 to 12 months after Rethymic treatment) which should include the following (“a”, “b”, and “c”) - medical record documentation of the standard of care supportive measures implemented must be submitted: 

a. Antimicrobial prophylaxis to prevent bacterial, fungal, and viral infections [at a minimum, this must include Pneumocystis jiroveci pneumonia (PJP) prophylaxis, usually with trimethoprimsulfamethoxazole (TMP-SMX)] 
b. Immunoglobulin replacement therapy 
c. Strict infection control, sanitation, and isolation protocols to limit exposure to infectious pathogens 

3.) To decrease the risk of graft-versus-host disease (GVHD), the indiviual will receive immunosuppressive therapy, if needed, prior to and/or after Rethymic treatment based on their disease phenotype (i.e., typical vs. atypical complete DiGeorge syndrome) and pre-treatment phytohemagglutinin (PHA) response in accordance with the recommendations in the Rethymic product labeling. Immunosuppressive therapies most often include anti-thymocyte globulin [rabbit] (Thymoglobulin), methylprednisolone, and cyclosporine.



Congenital athymia is an ultra-rare condition in which children are born without a thymus, causing vulnerability to life-threatening infections and immune dysregulation. The estimated incidence of congenital athymia in the US is approximately 17 to 24 infants per 4 million live births annually. The thymus is responsible for the development of mature T cells and is the only organ where thymocytes can mature, be selected, and survive to become naive T cells. T cells originate in the bone marrow as progenitor cells; however, the bone marrow does not contain the specialized tissue required for T-cell maturation. Without a functioning thymus, the inability to produce immunocompetent T cells leads to immunodeficiency manifested as increased susceptibility to infection. With only supportive care, children with congenital athymia typically do not survive beyond 2 to 3 years of age. Congenital athymia is often associated with other conditions, such as DiGeorge syndrome (a.k.a., 22q11.2 deletion syndrome); mutations in the genes TBX1, CHD7 (CHARGE syndrome - coloboma, heart defects, choanal atresia, growth or mental retardation, genital hypoplasia, and ear anomalies and/or deafness), and FOXN1 (FOXN1 deficiency); and diabetic embryopathy. These systemic conditions make the complex treatment of congenital athymia even more complicated. Early detection of congenital athymia is critical, as the sooner it is identified, the sooner isolation, infection prevention measures, and prophylactic antimicrobials can be initiated. Newborn screening plays a crucial role in early detection. Congenital athymia is initially detected through T-cell receptor rearrangement excision circle (TREC) screening, also known as severe combined immunodeficiency (SCID) screening. TREC screening provides the first indication of an immunologic issue in an infant’s T-cell development, and it is a standard part of the newborn screening panel, required in all 50 US states as of 2018. Low or undetectable TREC levels (i.e., a positive screening result) indicate the need for further testing including flow cytometry and genetic testing to confirm a diagnosis of congenital athymia. 


Complete DiGeorge Syndrome (cDGS) is a rare disorder in which children have no detectable thymus (athymia). Some individuals have DiGeorge syndrome as part of a larger disorder, specifically chromosome 22q11.2 deletion syndrome or CHARGE syndrome. Both of these disorders have symptoms affecting multiple systems of the body. DiGeorge syndrome typically refers to individuals who have T cell counts less than the 10th percentile for age, plus they have heart defects and/or low calcium levels. Many but not all of infants with 22q11.2 deletion syndrome and CHARGE syndrome have T cell counts less than the 10th percentile for age and are often referred to as having DiGeorge syndrome. (Children with 22q11.2 deletion syndrome or CHARGE syndrome who have normal T cell counts are not considered as having DiGeorge syndrome).

Only about 1% of children with DiGeorge syndrome have absence of the thymus. To determine that a child had no thymus, blood testing must not detect T cells emerging from the thymus. Newly developed T cells emerging from the thymus have special proteins on the cell surface. Those T cells are called “naïve" T cells. Children with 22q11.2 deletion syndrome or CHARGE syndrome who have very low naïve T cells counts (less than 50 per mm3 in the blood) are said to have complete DiGeorge syndrome. Children with complete DiGeorge syndrome are all athymic by definition. For affected infants who are infants of diabetic mothers and other infants with no identifiable genetic defects or syndromes, the cause of athymia remains unknown.

Researchers have identified several genes that, when altered (mutated), can cause absence of the thymus. These genes include the FOXN1, TBX1, TBX2, and the PAX1 genes. 


Allogeneic processed thymus tissue–agdc (Rethymic) was approved by the US Food and Drug Administration (FDA) in October 2021 for immune reconstitution in pediatric patients with congenital athymia. It is the first treatment to be approved for this fatal condition. The thymus tissue is obtained from donors less than or equal to 9 months of age undergoing cardiac surgery. The manufacturing process preserves the thymic epithelial cells and tissue structure and depletes most of the donor thymocytes from the tissue. The proposed mechanism of action involves the migration of recipient T cell progenitors from the bone marrow to the implanted thymus tissue, where they develop into naïve immunocompetent recipient T cells. Evidence of thymic function will be observed by the development of naïve T cells in the peripheral blood occurring at least 6 months after treatment. 

The efficacy of Rethymic leading to FDA approval was evaluated in 10 prospective, single-center, open-label studies that enrolled a total of 105 individuals, including 95 individuals in the primary efficacy analysis. The demographics and baseline characteristics of the individuals enrolled in the clinical studies were similar across studies. Across the efficacy population, 59% were male; 70% were White, and 22% were Black. The median age at the time of treatment was 9 months (range of 1 to 36 months). The diagnosis of congenital athymic was based on flow cytometry documenting fewer than 50 naïve T cells/mm3 (CD45RA+, CD62L+) in the peripheral blood or less than 5% of total T cells being naïve in phenotype for most patients (91 of 95). In addition congenital athymia, individuals also had complete DiGeorge syndrome (cDGS; also referred to as complete DiGeorge anomaly (cDGA)) if they also met at least one of the following criteria: congenital heart defect, hypoparathyroidism (or hypocalcemia requiring calcium replacement), 22q11 hemizygosity, 10p13 hemizygosity, CHARGE syndrome, or CHD7 mutation. Across the efficacy population, 93 individuals (98%) were diagnosed with cDGS, and the most common DiGeorge gene mutations or syndromic associations were chromosome 22q11.2 deletion (36 individuals; 38%) and CHARGE syndrome (23 individuals; 24%). There were 35 individuals with missing or no identified genetic mutations. Two (2%) individuals had FOXN1 deficiency, and 1 individual (1%) had a TBX variant. There were 50 (53%) individuals with typical cDGS; these individuals had congenital athymia with the absence of a T cellrelated rash. There were 42 (44%) individuals diagnosed with atypical cDGS; these individuals may have had a rash, lymphadenopathy, or oligoclonal T cells. Individuals who did not have congenital athymia (e.g., SCID) and individuals with prior transplants, including thymus and HCT, were excluded from the efficacy analysis population. Individuals with heart surgery anticipated within 4 weeks prior to, or 3 months after, the planned Rethymic treatment date, individuals with human immunodeficiency virus (HIV) infection, and individuals who were not considered good surgical candidates were excluded from study participation. Individuals in the efficacy population received Rethymic in a single surgical procedure at a dose of 4,900 to 24,000 mm2 of Rethymic per recipient body surface area (BSA) in m2 . Patients were assigned to receive immunosuppressive therapy prior to and/or after treatment according to their disease phenotype and pre-Rethymic phytohemagglutinin (PHA) response. No individuals were retreated with Rethymic. 

The Kaplan-Meier estimated survival rates were 77% (95% CI [0.670, 0.841]) at 1 year and 76% (95% CI [0.658, 0.832]) at 2 years. For individuals who were alive at 1 year after treatment, the survival rate was 94% at a median follow-up of 10.7 years. Without treatment, congenital athymia is fatal in childhood. In a natural history population observed from 1991 through 2017, 49 individuals diagnosed with congenital athymia received supportive care only. The 2-year survival rate was 6%, with all individuals dying by 3 years of age. The most common cause of death was infection in 26 (53%) individuals. Other common causes (≥10%) included support withdrawn in 7 (14%) individuals, respiratory arrest in 5 (10%) individuals, and cardiac arrest in 5 (10%) individuals. Rethymic also significantly reduced the number of infections over time. In the first year after treatment, the number of individuals with an infection event onset 6 to ≤12 months after treatment decreased by 38% (from 63 to 39) relative to the number of individuals with an infection event onset in the first 6 months post-treatment. A two-year analysis showed a decrease in both the number of individuals with an infection event and the mean number of infection events per individual, with an onset in the first 12 months post-treatment as compared to 12 to ≤24 months after treatment. There was a mean difference of 2.9 events (p<0.001) per individual. Following Rethymic treatment., naïve CD4+ and CD8+ T cells reconstituted over the first year, with a durable increase through Year 2. Median (minimum, maximum) naïve CD4+ T cells/mm3 increased from a baseline of 1 (0, 38) to values of 42 (0, 653), 212 (1, 751), and 275 (33, 858) at 6, 12, and 24 months after treatment, respectively. Median naïve CD8+ T cells/mm3 increased from a baseline of 0 (0, 46) to values of 9 (0, 163), 58 (0, 304), and 86 (6, 275) at 6, 12, and 24 months after treatment, respectively. This was accompanied by functional improvements based on T cell proliferative responses to PHA.​


Elsevier's Clinical Pharmacology Compendium. Allogeneic Processed Thymus Tissue. 10/17/2021. [Clinical Key Web site]. Available at: [via subscription only]. Accessed February 8, 2024.

Collins C, Kim-Chang JJ, Hsieh E, Silber A, O'Hara M, Kulke S, Cooper MA. Economic burden of congenital athymia in the United States for patients receiving supportive care during the first 3 years

of life. J Med Econ. 2021 Jan-Dec;24(1):962-971.

Collins C, Sharpe E, Silber A, et al. Congenital Athymia: Genetic Etiologies, Clinical Manifestations, Diagnosis, and Treatment. J Clin Immunol. 2021 Jul;41(5):881-895. Epub 2021 May 13.

Gupton SE, McCarthy EA, Markert ML. Care of children with DiGeorge before and after cultured thymus tissue implantation. J Clin Immunol. 2021;41(5):896-905.

Hsieh EWY, Kim-Chang JJ, Kulke S, et al. Defining the clinical, emotional, social, and financial burden of congenital athymia. Adv Ther. 2021;38(8):4271-4288.

Markert ML, Gupton SE, McCarthy EA. Experience with cultured thymus tissue in 105 children. J Allergy Clin Immunol. 2021 Aug 3:S0091-6749(21)01056-3. Epub ahead of print.

Orphan Drug Designations and Approval [Internet]. Silver Spring (MD): US Food and Drug Administration; 2021. Available from: Search Orphan Drug Designations and Approvals ( February 8, 2024.

RETHYMIC (Allogeneic processed thymus tissue–agdc). [prescribing information]. Marlborough, MA: Sumitomo Pharma America, Inc.; 07/2023. Available at:  RETHYMIC® (allogeneic processed thymus tissue-agdc). Accessed February 8, 2024.

US Food and Drug Administration (FDA). Vaccines, Blood & Biologics: Rethymic Package Insert (10/2021) and Approval Letter. Site updated 11/04/2021. RETHYMIC | FDA. Accessed February 8, 2024. 


CPT Procedure Code Number(s)

ICD - 10 Procedure Code Number(s)

ICD - 10 Diagnosis Code Number(s)
Q89.8 Other specified congenital malformations

Q89.9 Congenital malformation, unspecified

HCPCS Level II Code Number(s)

C9399 Unclassified drugs or biologicals

J3590 Unclassified biologics​

Revenue Code Number(s)

Coding and Billing Requirements

Policy History

Medical Policy Bulletin