title: Chemotherapeutic sensitivity of acute lymphoblastic leukemia cells in culture: correlation with clinical efficacy on donor patients.
abstract: The establishment of permanent acute lymphocytic leukemia (ALL) lines of different phenotypes permits the study of their sensitivity to chemotherapeutic agents. The sensitivity of four ALL cell lines, two T-cell lines and one each of B- and non-T/non-B cell lines, to eight chemotherapeutic agents was studied by means of clonogenic assay. Response data were analyzed by two criteria--one based on concentrations obtainable from the elimination phase and the other based on peak concentration--both derived from pharmacokinetic studies in man. The overall correlation between the two criteria was good and only in 5 of 32 occasions were there major discrepancies. A retrospective analysis of the clinical course of the four donor patients showed that although the one set of criteria gave a positive correlation of asparaginase response in vivo, the other positively correlated the daunorubicin response, but not vice versa. No new cut-off line could be drawn to satisfy completely in vitro/in vivo correlation for all the drugs. Although the possibility exists that a leukemic cell line may not actually be predictive of chemotherapeutic responsiveness in the donor patients, our data indicate a need to reexamine the in vitro system in predictive testing of antileukemic agents.
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001215:Asparaginase / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002648:Child; D003114:Colony-Forming Units Assay; D003630:Daunorubicin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D007945:Leukemia, Lymphoid / Q000188:drug therapy / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D014410:Tumor Stem Cell Assay; D014747:Vinblastine / Q000494:pharmacology; D014750:Vincristine / Q000494:pharmacology; D009353:Zinostatin / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D014750:Vincristine; D014747:Vinblastine; D003907:Dexamethasone; D004317:Doxorubicin; D009353:Zinostatin; D001215:Asparaginase; D006854:Hydrocortisone; D003630:Daunorubicin