title: Ex vivo assessment of drug response by differential staining cytotoxicity (DiSC) assay suggests a biological basis for equality of chemotherapy irrespective of age for patients with chronic lymphocytic leukaemia.
abstract: With a mean age at diagnosis for chronic lymphocytic leukaemia (CLL) of 65 years, development of optimal therapeutic regimens has been hampered by the advanced age of patients. In general, because of comorbidity older patients are not treated with the intent of achieving a complete response and so do not attain the quality of response of younger patients and do not survive as long. We have investigated whether or not ex vivo cellular sensitivity to cytotoxic drugs could be an underlying biological basis for this age differential in response and survival by comparing ex vivo drug response with age in untreated CLL patients. Cells from 365 untreated CLL patients aged 31.1-87.1 years (average 65.3 years) were tested for drug response by differential staining cytotoxicity (DiSC) assay with a panel of 10 drugs. An average of 280 results (range 196-361) obtained for each drug was compared with patient age. For chlorambucil, cyclophosphamide, prednisolone, vincristine, doxorubicin, epirubicin, fludarabine, cladribine and methylprednisolone, no relationship was found between ex vivo drug response and age (r<0.12). For pentostatin, a possible but very weak relationship (r = 0.18; n = 210; P = 0.06) was found. We conclude that cellular sensitivity to cytotoxic drugs does not support the differential treatment of older and younger CLL patients.
authors.affiliation: Bath Cancer Research, Wolfson Centre, Royal United Hospital, UK.
authors.forename: A G
authors.initials: AG
authors.lastname: Bosanquet
authors.forename: M I
authors.initials: MI
authors.lastname: Bosanquet
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002699:Chlorambucil / Q000494:pharmacology; D017338:Cladribine / Q000494:pharmacology; D015897:Comorbidity; D003520:Cyclophosphamide / Q000031:analogs & derivatives / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D015251:Epirubicin / Q000494:pharmacology; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008775:Methylprednisolone / Q000494:pharmacology; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D010166:Palliative Care; D015649:Pentostatin / Q000494:pharmacology; D011239:Prednisolone / Q000008:administration & dosage; D011379:Prognosis; D013194:Staining and Labeling; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014740:Vidarabine / Q000031:analogs & derivatives / Q000494:pharmacology; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D000970:Antineoplastic Agents; D002699:Chlorambucil; D015649:Pentostatin; D015251:Epirubicin; D017338:Cladribine; C048341:mafosfamide; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011239:Prednisolone; D014740:Vidarabine; C024352:fludarabine; D008775:Methylprednisolone