title: Pretreatment leukaemia cell drug resistance is correlated to clinical outcome in acute myeloid leukaemia.
abstract: In 85 adult patients diagnosed with acute myeloid leukaemia (AML) and treated at the same institution during a 5-yr period, the clinical significance of in vitro cellular drug resistance to the anthracyclines aclarubicin (Acla) and daunorubicin (Dau) as well as the nucleoside analogue cytarabine (Ara-C) was investigated using a 4-d MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay. In 59 patients of whom 40 were treated by the combination of Acla and Ara-C we found that leukaemia cell drug resistance towards Acla was higher (by a factor 2.80) in patients who failed to enter complete remission (CR) after the first cycle of induction chemotherapy as compared to patients who entered complete remission. The relationship was significant in univariate as well as multivariate analysis (p=0.02 and 0.03, respectively). By contrast, no in vitro single drug resistance values were consistently correlated to other parameters of clinical outcome (overall CR rate, overall survival (OS), or continuous complete remission (CCR)), whereas the combined Acla and Ara-C drug resistance profile (Acla/Ara-C DRP) was of prognostic significance to overall survival of all 85 patients (p=0.004) as well as to the CCR of 39 complete responders (p=0.04). These findings remained statistically significant in multivariate analyses correcting for other variables influencing clinical outcome including patient age, leukocyte count, karyotype, FAB-subtype, and presence/absence of secondary AML. We conclude that the in vitro drug resistance of leukaemia cells at time of disease presentation appears to be independent of prognostic significance to short- and long-term clinical outcome in AML.
authors.affiliation: Department of Medicine and Haematology, Aarhus University Hospital, DK-8000 Aarhus C, Denmark. janmaxgard@dadlnet.dk
authors.forename: J M
authors.initials: JM
authors.lastname: Nørgaard
authors.forename: S T
authors.initials: ST
authors.lastname: Langkjer
authors.forename: T
authors.initials: T
authors.lastname: Palshof
authors.forename: B
authors.initials: B
authors.lastname: Pedersen
authors.forename: P
authors.initials: P
authors.lastname: Hokland
mesh_terms: D015250:Aclarubicin / Q000008:administration & dosage / Q000494:pharmacology*; D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000677:Amsacrine / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage / Q000494:pharmacology*; D003630:Daunorubicin / Q000008:administration & dosage / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D011379:Prognosis; D012074:Remission Induction; D016019:Survival Analysis; D013866:Thioguanine / Q000008:administration & dosage; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000677:Amsacrine; D003561:Cytarabine; D005047:Etoposide; D015250:Aclarubicin; D008942:Mitoxantrone; D013866:Thioguanine; D015255:Idarubicin; D003630:Daunorubicin