Anti-thymocyte Immunoglobulins (ATG)

Indication

Rejection resistant to steroids is now uncommon but ATG may be used in some circumstances, e.g., persistent biopsy-proven rejection despite two courses of methylprednisolone.

Contra-indications

known allergy to rabbit proteins

acute viral illness

full anaphylactic response to the test dose.

The aim of therapy is to suppress the absolute CD3 cell count (T cell count) to below 0.05x10⁹/L (<50/microlitre) for 14 days. ATG is given daily until the CD3 cell count has reached this level, then repeated if it rises above this level. Response varies, but most patients need 2-3 full doses over the 14 day treatment period. A test dose is given and followed 24h later by the first full dose.

Test dose

Symptoms during or after an ATG infusion are common. This is due to a systemic inflammatory response which occurs when T cells are activated by binding ATG. Symptoms of this 'cytokine release syndrome' inculde headache, fever, arthralgia, rigors and hypotension. Pulmonary oedema may occur in severe cases. True anaphylaxis is rare but it may occur.

All patients should have a test dose first, to identify those who will develop severe reactions including anaphylaxis.

Signs of anaphylaxis are tingling in the extremities and around the mouth, swelling of the lips and larynx, bronchospasm, tenesmus, hypotension. It should be treated in the usual way with hydrocortison 100mg IV, chorpheniramine 10mg IV; 0.5ml adrenaline 1:1000 IM may be necessary.

• Give 5 mg ATG in 100ml NaCl 0.9% infused through a peripheral vein over 1 hour. Have hydrocortisone, chlorpheniramine and adrenaline available close by.
• Premedicate with paracetamol 1g orally, chlorpheniramine 10mg IV.
• Reconstitute the contents of one vial (25mg) with accompanying diluent (5 ml water for injections), giving a solution of 5 mg ATG per ml.

• Take 1 ml of solution and add to 100 ml NaCl 0.9%.

• Observe patient closely, monitoring BP, pulse and temperature according to the following schedule:

Give ATG 2mg/kg in 0.9% NaCl given over 6-8h via a central venous catheter. Round the dose to the nearest 25mg.
Reconstitute required number of vials with 5ml diluent per vial.
Add contents of reconstituted vials to 0.9% NaCl, allowing 50ml per vial (250ml bag usually appropriate).
Premedicate as for test dose, but if the patient experienced systemic symptoms with the test dose, consider hydrocortison 100mg IV in addition to any oral prednisolone they are taking as part of their baseline immunosuppression.
Observations as for test dose

Monitoring

• Daily absolute CD3 count whilst treated. In Edinburgh send a second FBC tube to the WGH haematology lab (tel 31914) urgently first thing every morning, using a separate request form. Same-day result will be provided.
• Daily FBC and U+E during treatment and over next 2 weeks.
• Interrupt treatment if platelet count <50x10⁹/L.
• Consider interrupting treatment if leukocytes <2x10⁹/L.

Monitoring

See also Test Dose section. Symptoms of some sort are common (approx 25%) during administration and may be unpleasant for the patient. They include rigors (4%), fever (15%), arthralgia (10%), erythema (10%) and pruritic skin eruptions (10%). Symptoms are most commonly seen after the first injection and decrease during the course of treatment.

Other side effects include thrombocytopenia (5%), neutropenia (5%) which may prevent continuation of the treatment course, and serum sickness. Severe cytokine release syndrome and true anaphylaxis are rare (<1%) but can be fatal.

Interactions

There is a risk of over-immunosuppression, hence the following schedule should be followed:

* Depending on T cell count

Tacrolimus reinstated after 1 week at dose of 0.05mg/kg divided into two doses [or half previous established dose]. Ciclosporin at dose 3mg/kg divided into two doses [or half previous doses].

Continue PCP and CMV/HSV prophylaxis for 3 months after treatment with ATG.

Ordering

Mon - Fri 08:30 - 17:00 - Contact unit pharmacist. Out of hours contact the resident pharmacist, bleep 2268. A small stock is held in pharmacy.

Storage

Both the dry powder and reconstituted solution should be stored in fridge (+4C), usually on ward 117; protect from light.

Transplant protocols developed on the Edinburgh Transplant Unit. This page first published March 2002 by Amit Adlakha, extensively reviewed November 2006 by Angela Webster, and last modified Monday, August 10, 2009.

NOTE that the accuracy of any statements in this information CANNOT be guaranteed. It is published in the belief that it is correct, and we endeavour to keep it so - but we do make mistakes. Furthermore, over some subjects there are differing opinions, or differing degrees of certainty. We have usually not attempted to discuss these here because the aim has been to provide an immediate and brief guide. In all areas, prior medical knowledge is assumed. The EdRenHANDBOOK is not suitable for use by those without such a background. Contact us by email or at the address given at the foot of the contents page with any comments or corrections.