POLYCLONAL ANTITHYMOCYTE-SERUM - IMMUNE PROPHYLAXIS AND REJECTION THERAPY IN PEDIATRIC HEART-TRANSPLANTATION PATIENTS

Antithymocyte serum (ATS), a polyclonal antibody preparation raised in rabbits, has been used as rescue therapy for severe rejection and ind uction of immune prophylaxis in our pediatric patients with heart tran splants. To evaluate the customized pediatric ATS dosages, circulating plasma levels of unbound ATS were measured by an indirect flow cytome tric analysis. ATS blood levels and their effects on in vitro lymphocy te function (mixed lymphocyte culture), peripheral blood lymphocyte su bsets (immunophenotyping), and in vivo response, as measured by echoca rdiographic or biopsy data, were studied in three pediatric transplant patient groups. Detectable levels of circulating ATS were present 24 hours after infusion and correlated with the decrease in CD2 + periphe ral blood lymphocytes. As expected, detectable ATS levels were measure d only in the ATS treatment groups. Significant differences in lymphoc yte subsets were seen between patients receiving ATS and those never r eceiving ATS (p < 0.01), with the non-ATS patients having normal lymph ocyte subset percentages (CD2 = 60% +/- 29%). The mixed lymphocyte cul ture response was suppressed to a greater degree in the ATS therapy gr oups (86% vs 75%, p < 0.02), although these results were confounded by the use of high-dose steroids in all groups, which inhibit allogeneic responses. We conclude that effective immunologic monitoring of ATS t herapy can be accomplished by peripheral blood lymphocyte subset deter minations and ATS serum levels.