Assessment of drug activity and proliferation ex vivo for prediction of outcome in aggressive non-Hodgkin's lymphomas

Abstract

The activity of cytotoxic drugs and tumour cell proliferation rate were assessed ex vivo using the fluorometric microculture cytotoxicity assay (FMCA) and stainings for Ki67 and mitosis in 40 patients with aggressive non-Hodgkin's lymphomas (NHL). The findings were correlated to clinical response and survival. Twenty-three patients had a complete remission and 10 a partial remission. A drug sensitivity index based on the cell survival for three major drugs in NHL treatment was derived empirically and proliferation was expressed as low-, intermediate- or high. In 5 out of 8 drugs tested, cell survival ex vivo was higher in clinical non-responders than that in responders. Using the median drug sensitivity index as a cut-off, the sensitivity and specificity for tumour response were 58% and 100%, respectively, and was similar for the proliferation index. Both indices combined increased the sensitivity to 73% at retained specificity. Intermediate/high proliferation was significantly associated with impaired survival, whereas the drug sensitivity index was not predictive of survival. Thus, ex vivo assessments of drug sensitivity and proliferation seem to provide prognostic information in aggressive NHL.