A new extracorporeal reactor-dialyzer for enzyme therapy using immobilized L-asparaginase

Depletion of circulating L-asparagine has proved beneficial in the treatment of some acute lymphoyctic leukemias. To avoid the immunologic sequelae of administering L-asparaginase parenterally, we have covalently attached the enzyme to the outside of the fibers of a conventional hollow fiber hemodialyzer. This provides ready access of the substrate to the enzyme, while simultaneously isolating the foreign protein from the immune system. Such reactor-dialyzers perform well, both in vitro and in vivo. Circulating L-asparagine in the healthy dog is reduced from about 50 micrometer to less than 2 micrometer within 30 min of connecting the reactor-dialyzer and the reduction persists for at least 4 hr after cessation of treatment.