Complement-dependent and complement-independent cytotoxicity of polyclonal antithymocyte globulins in chronic lymphocytic leukemia.

OBJECTIVE

Despite important progress in its management, chronic lymphocytic leukemia (CLL) remains incurable with standard therapies. Allogeneic stem cell transplantation (SCT) is a potentially curative therapy for patients with CLL. Polyclonal antithymocyte (or anti-T-cell) globulins (ATGs) are used for conditioning in allogeneic SCT mainly due to their anti-T-cell activity. ATGs however, contain antibodies targeting antigens expressed on various hematopoietic cells including B cells.

METHODS

We assessed anti-CLL activity of two commercially available ATG preparations at clinically relevant concentrations (10-100 microg/ml) in CLL samples from 16 patients. Cytotoxicity was determined by staining with 7-amino-actinomycin D (7-AAD), annexin V and flow cytometry.

RESULTS

Both ATG preparations induced marked complement-independent dose-dependent cytotoxicity in all samples. Addition of complement strongly enhanced the cytotoxic effect of both ATG preparations significantly. ATG-induced complement-dependent cytotoxicity (CDC) was at least as high as that observed with Alemtuzumab. Both ATGs enhanced the cytotoxic effect of Fludarabine.

CONCLUSION

ATG is an effective agent against CLL in vitro. We suggest that this potential be taken into consideration when developing stem cell transplantation protocols for patients with CLL.