title: Prediction of individual response to chemotherapy in patients with acute myeloid leukaemia using the chemosensitivity index Ci.
abstract: As the response to chemotherapy in patients with acute myeloid leukaemia (AML) may still not be accurately determined by known prognostic factors, such as karyotype, the ex vivo chemosensitivity profile may help to predict the individual response. The predictive accuracy of an ex vivo assay should be assessed by correlation of assay results with both response rate and survival. We prospectively investigated the prognostic relevance of pre-therapeutic ex vivo chemosensitivity testing in primary cell cultures from adult AML patients by applying a new evaluation methodology, designated the chemosensitivity index, C(i). This C(i) was designed as a prognostic index by taking the area under the curve as an exact measure of the total dose-response relationship. We found an overall predictive accuracy of 98.2% concerning treatment response, which compares favourably with previously published data ranging from 75% to 92%. Moreover, the C(i) proved to be the strongest prognostic factor for overall survival in a multivariate Cox regression analysis including karyotype grouping and age (P < 0.001), and enabled the evaluation of response to combination therapies and selection of possible treatment alternatives. Our data suggest that ex vivo chemosensitivity testing evaluated by the C(i) could serve as a powerful tool for assay-directed therapy strategies in AML.
authors.affiliation: Clinic I for Internal Medicine, University of Cologne, D-50924 Cologne, Germany. peter.staib@uni-koeln.de
authors.forename: Peter
authors.initials: P
authors.lastname: Staib
authors.forename: Elke
authors.initials: E
authors.lastname: Staltmeier
authors.forename: Katja
authors.initials: K
authors.lastname: Neurohr
authors.forename: Oliver
authors.initials: O
authors.lastname: Cornely
authors.forename: Marcel
authors.initials: M
authors.lastname: Reiser
authors.forename: Timo
authors.initials: T
authors.lastname: Schinköthe
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D004354:Drug Screening Assays, Antitumor / Q000379:methods / Q000592:standards; D005260:Female; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D013866:Thioguanine / Q000008:administration & dosage; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured
chemical_list: D003561:Cytarabine; D008942:Mitoxantrone; D013866:Thioguanine; D003630:Daunorubicin