Thymoglobulin

• Events surrounding the renal transplant procedure and initial hospitalization are important determinants of long-term allograft function.
  

• The initial immunosuppressive regimen may have a significant impact on these events although this is not predictable and is controversial. "Induction
  

• immunosuppressive therapy" generally refers to the use of anti-lymphocyte antibodies at the time of transplant which includes both monoclonal antibodies such as OKT3 or polyclonals such as ATGAM, ALG, or Thymoglobulin.
  
• The theoretical advantages with antibodies are to avoid the use of vasoconstrictive calcineurin inhibitors such as Neoral or Prograf in the immediate posttransplant period and to block immune interactions at the time of transplant.

• It is important to note that release of cytokines with antibodies may increase the risk of coagulation in some allografts. The combined immunological effects may improve early allograft function, delay or prevent rejection, and improve longterm allograft survival.
  

• Several studies have demonstrated that there are advantages of the use of antilymphocyte induction therapy in high-risk groups and perhaps in low-risk groups. Induction therapy, however, is associated with ncreased initial expense, increased risk for cytomegalovirus (CMV) disease, and posttransplant lymphoproliferative disease (PTLD). Also long term studies beyond 3 years suggest that long term survival is not predictably improved by induction therapy.
  

• Both monoclonal and polyclonal agents have been used for induction therapy. Polyclonal agents may have an advantage over monoclonal antilymphocyte therapy in the number of “target” that can be blocked.
  

• ATGAM (Pharmacia-UpJohn, Kalamazoo, MI) is available for induction immunosuppressive therapy and is obtained by immunization of horses with human thymocytes. It contains antibodies to a wide variety of human T-cell surface antigens including CD3, LFA-1, and CD45 as well as major histocompatibility complex (MHC) antigens. However some patients are sensitized to horse proteins prior to transplant, while others develop sensitization after exposure to Atgam.
  

• Thymoglobulin (SangStat Medical Corporation, Menlo Park, CA) is a polyclonal immunosuppressive agent similar to Atgam but is produced in the rabbit. Both Atgam and Thymoglobulin have been shown to reverse acute rejection as well as being useful in induction therapy. Unlike ATGAM, Thymoglobulin is pasteurized and is thought to have less batch-to-batch variability as well as being slightly less expensive at an equipotent dose. There is limited data that it may also have better effect in preventing rejection and for this reason we have adopted it for primary therapy in induction.
  

Indications:
• High risk immunological patients (previous severe rejections, high PRA
with historical T or B cell positivity)
• Delayed graft function in marginal or comprimised donors
• Steroid resistant rejection and unable to administer OKT3, ATGAM

Administration
Thymoglobulin is contraindicated in patients with a known allergy to rabbit
protein.
Thymoglobulin should be started in the operating room following vascular
anastamosis. This obviously requires communication with the anesthesist prior
to the patient going to the operating room. If it is not possible to give in the
operating room, administration should not be delayed beyond the recovery
room.
Infusion should occur into a central vein over 4-12 hrs. A 0.2-0.22 micron in-line
filter may be used, but is not absolutely required. Infusions prepared in saline
are stable for 20 hours from time of preparation.

Dose and Dose Adjustment
• The initial dose i s 1.5 mg/kg/day with a range of 1.25-2.5 mg/kg/day to
achieve a lymphocyte count of approximately 100/mm3. Thymoglobulin
should be diluted in 0.9% saline to a maximum concentration of 150 mg/500
ml (suggested dilution is 50 ml for each 25 mg vial). All infusions at University
Campus - LHSC should be ordered in 500 ml 0.9% saline.
•Pre-medication with diphenhydramine 25-50 mg and acetaminophen 30-60
minutes prior to infusion is advised. The usual daily dose of corticosteroid is
sufficient, and additional steroid is not required. The need for pre-medications
should be reviewed after the first 2 doses of Thymoglobulin.
• Dosage can be adjusted using absolute lymphocyte count from Hematology
or by CD2 counts using FACS. The latter is not necessary every day in most
patients.
• If the total WBC falls bel ow 2, 000 cells /mm3 or pl atelets fall below 50, 000
cells/mm3 , Thymoglobulin should be held
• If the total WBC is between 2,000 and 3,000, or the platelets are between
50,000 and 75,000, the next dose should be reduced by one-half
• CMV prophylaxis is absolutely required for CMV negative recipients of a
CMV positive kidney and highly suggested for if either the donor or recipient
are CMV positive recipients.
Thymoglobulin is available in vials containing 25 mg. Wherever possible the
total daily dose should be a multiple of 25 to help reduce cost due to drug
wastage as each 25 mg ampoule costs $173.00 CDN.
Duration of treatment for induction is until the creatinine is < style="font-weight: bold;">Side Effects
fever, chills, arthralgias, skin rashes, serum sickness (may be seen by end of 1st
week of treatment), leukopenia (more common with Thymoglobulin than
ATGAM), thrombocytopenia (rare), anaphylaxis (rare)