Appendix L. 
359 
steroid withdrawal is made after this time period, resulting in long- 
term success in about 80% of patients. Generally, there is no need for 
conventional induction agents when late withdrawal of steroids is 
done. 
Anti-Lymphocyte Antibody Therapy 
Despite the extensive use of induction therapy using anti-lymphocyte 
antibody in solid organ transplantation, their exact role is unclear. 
There is no doubt that routine use of these agents is unwarranted as 
the generalized immunosuppression induced by then increased the 
risk of infections and malignancy. Despite the lack of consistent data 
supporting the routine use of induction therapy with anti-lymphocyte 
antibody agents, there is a role in certain select situations. 
Specifically, patients with early post-operative renal or hepatic 
dysfunction may benefit especially by the avoidance of cyclosporine 
therapy while using these induction agents. Anti-lymphocyte 
antibody therapy can provide effective immunosuppression for 
atleast 10 to 14 days without CyA or tacrolimus therapy. It has also 
been suggested that patients with overwhelming postoperative 
bacterial infections or diabetics with severe postoperative 
hyperglycemia may benefit from the comparatively low doses of 
corticosteroids required during anti-lymphocyte induction therapy. 
The two main types of induction agents have been either the 
polyclonal antilymphocyte or antithymocyte globulins and more 
recently the murine monoclonal antibody OKT3. While these agents 
have been shovm to be effective in terminating acute allograft 
rejection and in treating refractory rejection, the results of 
comparative studies of outcomes v^ith and without monoclonal 
induction therapy have varied, with most studies demonstrating an 
effect on rejection that is maintained only while antibody therapy is 
ongoing. Without repeated administration, these agents only delay 
the time to a first rejection episode without decreasing the overall 
frequency or severity of rejection. More importantly, their use has 
been associated with an increased risk of short-term (infections) and 
long-term (lympho-proliferative disorders) complications. A 
complication specific to OKT3 is the development of a "flu-like 
syndrome" characterized by fever, chills and mild hypotension, 
typically seen with the first dose. 
Since antilymphocyte antibodies are produced in nonhuman 
species, their use is associated with the phenomenon of 
sensitization, leading to decreased effectiveness wnth repeated use 
as well as the possibilty of serum sickness. The development of 
sensitization has been linked with an increased risk of acute vascular 
PRE -PUBLICATION VERSION 
