In vitro determination of tumour chemosensitivity in haematological malignancies

Abstract

A four-day tumour chemosensitivity assay of potential use in predicting tumour response to cytotoxic drugs has been developed for haematological cancers. The method comprised isolation of white cells from peripheral blood or bone marrow aspirates, drug exposure and incubation for 4 days. Drug-induced tumour cell kill was assessed by differential staining of live and dead cells such that the former could be morphologically identified. Tumour cell viability was subsequently calculated by reference to an internal standard of fixed duck red blood cells. Over 30 drugs have been tested in vitro, all of which have shown a dose response relationship in vitro and given a good scatter of sensitivities from patient to patient within the concentration ranges tested. In 27 cases where the in vitro chemosensitivity could be compared with the in vivo response, there were 7 true positive comparisons (sensitive in vitro and in vivo), 17 true negative comparisons (resistant both in vitro and in vivo) and 3 false positive comparisons (sensitive in vitro, resistant in vivo). A result was obtained in 38 of 50 samples received, comprising 16 of 18 chronic lymphocytic leukaemias, 11 of 20 acute lymphoblastic leukaemias, 5 of 5 acute myeloid leukaemias and 6 of 7 myelomas. The assay appears to show considerable promise as a tumour chemosensitivity test and warrants wider investigations.