Allogeneic Processed Thymus Tissue

Allogeneic Processed Thymus Tissue is a prescription medication indicated for immune reconstitution in pediatric patients with congenital athymia.

• Allogeneic Processed Thymus Tissue is available under the following different brand names: Rethymic, allogeneic Processed Thymus Tissue-agdc.

Common side effects of Allogeneic Processed Thymus Tissue include:

• high blood pressure (hypertension)
• cytokine release syndrome
• rash
• low magnesium (hypomagnesemia)
• decreased kidney function/kidney failure
• low platelets (thrombocytopenia)
• graft versus host disease

Serious side effects of Allogeneic Processed Thymus Tissue include:

• not available

Rare side effects of Allogeneic Processed Thymus Tissue include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to the FDA at 1-800-FDA-1088.

Pediatric dosage

• Supplied as a single-dose unit, ready for use as slices of Processed Thymus Tissue, in sterile, polystyrene dishes (drug product dishes)
• Each drug product dish contains up to 4 slices, adhered to circular filter membranes on top of surgical sponges in 5 mL of medium containing fetal bovine serum
• Up to 42 slices are supplied according to the dosage calculated in advance by the manufacturer for the specific patient

Congenital athymia

Pediatric dosage

• Dosage determined by the surface area of the Allogeneic Processed Thymus Tissue slices and the recipient’s body surface area (BSA)
• The dose is calculated in advance by the manufacturer for the specific patient
• Recommended dose range: 5,000-22,000 mm2 of Allogeneic Processed Thymus Tissue surface area/m2 recipient BSA
• At the time of surgery, the manufacturing personnel communicate to the surgical team the portion of the product that represents the minimum dose
• Patients with evidence of maternal engraftment or elevated response to phytohemagglutinin (PHA) should also receive immunosuppressive medications

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Allogeneic Processed Thymus Tissue has severe interactions with no other drugs
• Allogeneic Processed Thymus Tissue has serious interactions with no other drugs
• Allogeneic Processed Thymus Tissue has moderate interactions with no other drugs
• Allogeneic Processed Thymus Tissue has minor interactions with no other drugs

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Allogeneic Processed Thymus Tissue?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Allogeneic Processed Thymus Tissue?”

Cautions

• Preexisting renal impairment is a risk factor for death
• Preexisting cytomegalovirus (CMV) infection may result in death before the development of thymic function; benefits/risks of treatment should be considered before treating patients with preexisting CMV infection
• Because of underlying immune deficiency, patients may be at risk of post-treatment lymphoproliferative disorder
• Monitoring
  • Monitor for development of autoimmune disorders, including complete blood cell counts with differential, liver enzymes, serum creatinine, urinalysis, and thyroid function
  • Monitor complete blood counts with differential weekly for the first 2 months post-treatment and then monthly through 12 months post-treatment
  • Liver enzymes including aspartate aminotransferase and alanine aminotransferase, serum creatinine levels, and urinalysis should be performed monthly for 3 months and then every 3 months through 12 months post-treatment
  • Thyroid function studies should be performed before treatment and then at 6 months and 12 months post-treatment; after 12 months, testing should be performed annually
  • Patients should be tested for Epstein-Barr virus (EBV) and CMV using PCR before and 3 months following treatment, or after any exposure to or suspected infection with CMV or EBV
  • If fever develops, assess the patient by blood and other cultures and treat with antimicrobials as clinically indicated
• Graft versus host disease
  • Monitor and treat patients at risk of developing graft versus host disease (GVHD); risk factors include atypical complete DiGeorge anomaly phenotype, prior hematopoietic cell transplant, and maternal engraftment
  • Patients with elevated baseline T-cell proliferative response to phytohemagglutinin (PHA) above 5,000 cpm or above 20-fold over background should receive immunosuppressive therapies to decrease the risk of GVHD; development of GVHD symptoms should be closely monitored and promptly treated
  • GVHD may manifest as fever, rash, lymphadenopathy, elevated bilirubin and liver enzymes, enteritis, and/or diarrhea
• Infection control and immunoprophylaxis
  • Immune reconstitution sufficient to protect from infection is unlikely to develop until 6-12 months after implantation; given the immunocompromised condition of athymic patients, follow infection control measures until the development of thymic function can be established
  • Maintain on immunoglobulin until all following criteria met
    • No longer on immunosuppression (greater than 10% of CD3+ T-cells are naïve in phenotype)
    • Greater than 9 months post-treatment
    • PHA response within normal limits
    • Normal serum IgA is desirable but not required
  • 2 months after stopping immunoglobulin, the IgG trough level should be checked
    • If the IgG trough level is normal range for age, the patient can remain off immunoglobulin replacement
    • If the IgG trough level is lower than the normal range for age, restart immunoglobulin replacement therapy and continue for a year before being retested using the above guidelines
• Before and after treatment, maintain the patient on Pneumocystis jirovecii pneumonia prophylaxis until all following criteria met
  • No longer on immunosuppression (greater than 10% of CD3+ T-cells are naïve in phenotype)
  • Greater than 9 months post-treatment
  • PHA response within normal limits
  • CD4+ T-cell count above 200 cells/mm3
• Transmission of serious infections and transmissible infections
  • Transmission of infectious disease may occur because the implants are derived from human tissue
  • Screen donors for increased risk of infection with HIV, human T-cell lymphotropic virus, HBV, HCV, Treponema pallidum, Trypanosoma cruzi, West Nile virus, transmissible spongiform encephalopathy agents, vaccinia, and Zika virus
  • Screen donors screened for clinical evidence of sepsis and communicable disease risks associated with xenotransplantation (eg, CMV)
• HLA
  • Anti-HLA antibodies
    • Screen for anti-HLA antibodies before treatment
    • Patients testing positive for anti-HLA antibodies should receive Allogeneic Processed Thymus Tissue from a donor who does not express those HLA alleles
  • HLA typing
    • HLA matching is required in patients who have received a prior hematopoietic cell transplantation (HCT) or a solid organ transplant
    • Patients who have received a prior HCT are at increased risk of developing GVHD after Allogeneic Processed Thymus Tissue if the HCT donor did not fully match the recipient
    • Minimize this risk by HLA matching to recipient alleles that were not expressed in the HCT donor
• Immunizations
  • Do not administer immunizations after implantation until immune-function criteria have been met
  • Inactivated vaccines: May administered once all of the criteria are met
    • Immunosuppressive therapies have been discontinued
    • IgG replacement therapy has been discontinued
    • Total CD4+ T-cell count above 200 cells/mm3 and there are more CD4+ T cells than CD8+ T cells (CD4+ above CD8+)
    • Limit inactivated vaccines to 2 vaccines/month
  • Live vaccines
    • Live virus vaccines should not be administered until patients have met the criteria for inactivated vaccines and received vaccinations with inactivated agents (eg, tetanus toxoid)
    • No additional vaccines (live or inactivated), except the inactivated influenza vaccine, should be given within 6 months after vaccination with a measles-containing vaccine or within 2 months after the varicella vaccine
    • Consider verifying response to vaccination with appropriate testing, in particular, varicella and measles

Pregnancy and Lactation

• Not available
• Lactation
  • Not available