Thymoglobulin at high concentrations binds complement resulting in direct cell lysis of lymphocytes.22 Anti-thymocyte globulins induce B cell apoptosis and do so preferentially to myelomonocytic and T-cell lines.41,42 Both myeloma cell lines and primary myeloma cells from patient bone marrow aspirates undergo apoptosis after exposure to thymoglobulin, as might be expected based on the apoptotic affect on B-cell lineages.38 Additionally both sets of cells undergo opsonization when complement is added in vitro. This demonstrates that thymoglobulin can induce myeloma cell kill by a number of methods and thus would be less susceptible to tumor resistance. The thymoglobulin binding sites have been assessed by competitive binding with monoclonal antibodies. Thymoglobulin binds competitively and specifically to IgG, HLA-ABC, HLA-DR, CD16, CD32, CD64, CD19, CD20, CD27, CD30, CD38, CD40, CD52, CD80, CD95, CD126, and CD138. Only IgG, CD16, CD64, and CD80 are not competitively bound. The apoptosis in primary cells can be inhibited by blocking the caspase, cathepsin D, or cathepsin B & D pathways. Zand et al also compared apoptotic response for five different lots of thymoglobulin. All lots apoptotic curves were overlapping over the range of 1-120 mcg/ml, demonstrating that very little lot to lot variation exists.43 This would be expected since each lot is derived from the combined sera of multiple immunized rabbits and thus individual differences in response for each rabbit would be mitigated. This may not be the case with lots of ATGAM each derived from a single horse. Each lot of thymoglobulin is already depleted of antibodies to red blood cells, has viruses inactivated and is tested for lymphocytotoxicity prior to release. The consistency demonstrated by Zand et al is consistent with the lack of observed variation in potency noticed in the greater than 20 years of clinical experience with this medication.