More acute lymphoid leukemia than acute myeloid leukemia blasts are killed by rabbit antithymocyte globulin

Rabbit antithymocyte globulin (ATG, thymoglobulin), a polyclonal antibody, is used to prevent graft-versus-host disease (GVHD) and graft failure in the setting of allogeneic hematopoietic cell transplantation (HCT). Recent in vitro studies suggest that ATG also has anti-leukemic activity. Whether acute lymphoid leukemia (ALL) or acute myeloid leukemia (AML) is more sensitive to ATG is not known. We used primary cells from 12 B-ALL and 38 AML patients and measured ATG-induced complement-dependent cytotoxicity (CDC) and complement-independent cytotoxicity (CIC) at clinically relevant ATG concentrations (10 and 50 mg/L). At 50 mg/L, ALL blasts were killed to a greater degree than AML blasts by CDC (median 96% vs 50% dead cells, P = 0.001) as well as CIC (median 23% vs 11% apoptotic cells, P = 0.049). At 10 mg/L, the difference was significant for CDC but not CIC. In conclusion, the anti-leukemic activity of ATG, particularly CDC, is more potent for ALL than AML in vitro. If this applies in vivo, ATG-based GVHD prophylaxis may be particularly advantageous for ALL.