Specific suppression of antibody rebound after extracorporeal immunoadsorption. I. Comparison of single versus combination chemotherapeutic agents.

The specific removal of circulating bovine serum albumin (BSA) antibodies in canine hosts with a BSA collodion charcoal extracorporeal immunoadsorbent is followed by a rebound and overshoot of specific antibody levels within 7 days after perfusion. Studies were carried out in dogs actively immunized to BSA and human serum albumin (HSA) to determine whether the post-immunoadsorption antibody rebound could be modified by the administration of various chemotherapeutic agents given alone or in combination, at various intervals in the post-perfusion period. Control extracorporeal immunoadsorption was carried out in each dog and its own pattern of post-perfusion antibody rebound was recorded. After a second extracorporeal perfusion, single drug chemotherapy with cyclophosphamide, methotrexate or cytosine arabinoside resulted in a slight delay, or had no effect on the recovery of antibody levels to pre-perfusion values. In contrast, dual (cyclophosphamide and cytosine arabinoside) or triple (cyclophosphamide, cytosine arabinoside and methotrexate) chemotherapy resulted in specific attenuation or arrest of BSA antibody rebound after specific immunoadsorption. BSA binding of serum rebounded to 62% of pre-perfusion values in one dog, but declined 37% and 22% below post-perfusion levels in two others. The immunosuppressive effect of dual or triple chemotherapy on BSA binding was specific, since control levels of HSA binding in sera were unchanged by the extracorporeal immunoadsorption and the chemotherapeutic treatment. Drug toxicity, including myelosuppression, diarrhoea and fever was transient and reversible upon cessation of treatment, but was more severe in dogs given a dual or triple drug treatment. Therefore, chemotherapeutic agents employed after extracorporeal immunoadsorption may result in specific reduction and lasting suppression of circulating antibody levels. Conclusions based on the number of dogs studied must be guarded, but these findings suggest a potentially effective therapeutic approach to many antibody mediated diseases.