title: Clonogenic growth patterns correlate with chemotherapy response in acute myeloid leukaemia.
abstract: Cytosine arabinoside and anthracycline-containing regimens induce remission in upwards of 60% of previously untreated patients with adult acute myeloid leukaemia (AML). Despite this, in addition to primary drug resistance, the majority of these patients relapse. Reliable methods for uniformly recognising these two subgroups at presentation do not exist and therefore a further attempt has been made to relate in vitro toxicity, using a clonogenic assay, to clinical outcome. In 10 normal controls and 12 chemotherapy naïve cases, mononuclear cells harvested by density gradient separation were re-suspended at a concentration of 2 x 10(5)/ml and quadruplicates of 250 microl per well cultured in methycellulose containing foetal calf serum and phytohaemagglutinin stimulated leucocyte conditioned medium. Cell kill was determined for cytosine arabinoside, daunorubicin and etoposide either singly or in combination using both a pulsed and continuous exposure. Aggregates were scored after seven days and three distinct patterns recognised. The patients all received the same drugs in a standard protocol and achievement of complete remission correlated with growth pattern. The survival of normal marrow colony-forming cells or GM-CFUc and the leukemic equivalent designated L-CFUc were assessed and a sensitivity index (SI) determined as a ratio of these two values in which more reproducible results were found when the drug was continuously present. It is concluded that the microculture technique is feasible and clearly demonstrates chemotherapy effect but no correlation was demonstrated with clinical outcome. This is a negative pilot study and, as a means of recognising drug sensitivity or resistance, should be discarded in favour of currently available molecular techniques.
authors.affiliation: The Department of Haematology and Bone Marrow Transplant Unit, The Searll Research Laboratory for Cellular and Molecular Biology Constantiaberg Medi-Clinic, Burnham Road, Plumstead 7800, Cape Town, South Africa. haematol@icon.co.za
authors.forename: Peter
authors.initials: P
authors.lastname: Jacobs
authors.forename: Lucille
authors.initials: L
authors.lastname: Wood
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002470:Cell Survival / Q000187:drug effects; D003561:Cytarabine / Q000627:therapeutic use; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D023461:Myeloid Progenitor Cells / Q000378:metabolism / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D010865:Pilot Projects; D011237:Predictive Value of Tests; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D003561:Cytarabine