USE OF RABBIT ANTITHYMOCYTE GLOBULIN IN CARDIAC TRANSPLANTATION - RELATIONSHIP OF SERUM CLEARANCE RATES TO CLINICAL OUTCOME

Serum rabbit globulin (RG) clearance rates were determined in 30 consecutive cardiac transplant recipients by radioimmune assay of serum RG levels after completion of an initial postoperative course of rabbit anti-human thymocyte globulin (RATG). Twenty patients who exhibited rapid RG elimination rates (average half-life, 1.6 days) had a rejection onset time of 16.2 days, rejection frequency of 3.9 episodes/100 patient days, and a 1-yr survival rate of 59%, respectively; this is in contrast to 28.3 days, 1.9 episodes/100 patient days and 80%, respectively, for the 10 patients with more prolonged initial RG elimination rates (average half-life, 11.4 days). Nineteen patients received 1 or more repeat courses of RATG. In 16 of these, a progressive increase in RG half-life during subsequent RATG administration could be demonstrated. A close correlation was observed between total RATG doses given in the initial course and peak serum levels of RG obtained (r = 0.82) and between onset of rejection and initial half-life RG (r = 0.69). This latter correlation was improved by the elimination of 1 of the 30 patients (r = 0.81) or by considering only those patients treated from a single RATG batch (r = 0.85; n = 15). No significant relationship was detected between any of the parameters assayed and total RATG dose, or rosette inhibition titers of RATG administered. Survival and rejection parameters of the first 30 patients receiving RATG were compared with the previous 20 receiving equine anti-thymocyte globulin. Rejection onset was 20 vs. 12 days, rejection frequency was 3.1 vs. 5.0 episodes/100 patient days, and graft survival at 1 yr was 66 vs. 41% for the RATG-equine antithymocyte globulin-treated patients, respectively. From these data it was concluded that: RATG administration favorably affects transplantation outcome; RATG half-life was the most important variable governing RATG effectiveness; variation in rosette inhibition titers within RATG batches were of minimal clinical importance; and monitoring of serum RG levels provided a necessary and rational basis for effective modulation of immunosuppressive therapy.