Monitoring anti-thymocyte globulin (ATG) in bone marrow recipients

Abstract

The present study was undertaken to acquire a rationale for clinical dose adjustment of anti-thymocyte globulin (ATG) to improve cost effectiveness and safety of graft-versus-host disease prophylaxis. The concentration of rabbit ATG in the serum of 12 patients was measured by ELISA and by the inhibitory effect on phytohaemagglutinin-induced blastogenesis. At 10 mg/ml ATG, ³H-thymidine incorporation was effectively blocked. Serial two-fold dilution of ATG showed that this effect decreased in a concentration-dependent manner and was lost at 10 ng/ml ATG. One hundred microlitres serum taken at day −1 to +22 post transplant effected significant inhibition of the phytohaemagglutinin-response with 49 ± 12% c.p.m. (x ± s.d.) on day +1 post transplant compared to 93 ± 13% c.p.m. on day −1 (P < 0.001, unpaired one-sided t-test). The rabbit-IgG was maximal at a concentration of 907 ± 187 μl/ml at day 0. Subsequently, it decreased with time. While rabbit-IgG was detectable for a long period (eg 160 μg/ml at day +22 in patient MD), the effect on the phytohaemagglutinin-response of normal mononuclear cells lasted up to 4 days post transplant. We conclude that 90 mg/kg body weight ATG-Fresenius given prior to marrow transplant leads to sustained T cell immunosuppression post transplant.