Clonogenic growth patterns correlate with chemotherapy response in acute myeloid leukaemia
Date
2005
Authors
Jacobs P.
Wood L.
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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 resuspended at a concentration of 2 × 105/ml and quadruplicates of 250 μl 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. © 2005 Taylor & Francis Group Ltd.
Description
Keywords
anthracycline antibiotic agent, cytarabine, daunorubicin, etoposide, acute granulocytic leukemia, adolescent, adult, article, cell aggregation, cell cycle, cell growth, cell killing, cell stimulation, cell survival, clinical article, clonogenesis, colony forming cell, colony forming unit GM, controlled study, density gradient, drug activity, drug exposure, drug resistance, drug sensitivity, female, hematopoiesis, human, human cell, leukocyte, male, mononuclear cell, priority journal, remission, sensitivity analysis, treatment outcome, treatment response, Adolescent, Adult, Antineoplastic Agents, Cell Survival, Cytarabine, Female, Humans, Leukemia, Myelocytic, Acute, Male, Middle Aged, Myeloid Progenitor Cells, Pilot Projects, Predictive Value of Tests, Treatment Outcome, Tumor Cells, Cultured, Tumor Stem Cell Assay, Tumor Stem Cells
Citation
Hematology
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