Clonogenic growth patterns correlate with chemotherapy response in acute myeloid leukaemia

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dc.contributor.authorJacobs P.
dc.contributor.authorWood L.
dc.date.accessioned2011-05-15T16:16:31Z
dc.date.available2011-05-15T16:16:31Z
dc.date.issued2005
dc.description.abstractCytosine 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.
dc.description.versionArticle
dc.identifier.citationHematology
dc.identifier.citation10
dc.identifier.citation4
dc.identifier.issn10245332
dc.identifier.other10.1080/10245330500141622
dc.identifier.urihttp://hdl.handle.net/10019.1/13818
dc.subjectanthracycline antibiotic agent
dc.subjectcytarabine
dc.subjectdaunorubicin
dc.subjectetoposide
dc.subjectacute granulocytic leukemia
dc.subjectadolescent
dc.subjectadult
dc.subjectarticle
dc.subjectcell aggregation
dc.subjectcell cycle
dc.subjectcell growth
dc.subjectcell killing
dc.subjectcell stimulation
dc.subjectcell survival
dc.subjectclinical article
dc.subjectclonogenesis
dc.subjectcolony forming cell
dc.subjectcolony forming unit GM
dc.subjectcontrolled study
dc.subjectdensity gradient
dc.subjectdrug activity
dc.subjectdrug exposure
dc.subjectdrug resistance
dc.subjectdrug sensitivity
dc.subjectfemale
dc.subjecthematopoiesis
dc.subjecthuman
dc.subjecthuman cell
dc.subjectleukocyte
dc.subjectmale
dc.subjectmononuclear cell
dc.subjectpriority journal
dc.subjectremission
dc.subjectsensitivity analysis
dc.subjecttreatment outcome
dc.subjecttreatment response
dc.subjectAdolescent
dc.subjectAdult
dc.subjectAntineoplastic Agents
dc.subjectCell Survival
dc.subjectCytarabine
dc.subjectFemale
dc.subjectHumans
dc.subjectLeukemia, Myelocytic, Acute
dc.subjectMale
dc.subjectMiddle Aged
dc.subjectMyeloid Progenitor Cells
dc.subjectPilot Projects
dc.subjectPredictive Value of Tests
dc.subjectTreatment Outcome
dc.subjectTumor Cells, Cultured
dc.subjectTumor Stem Cell Assay
dc.subjectTumor Stem Cells
dc.titleClonogenic growth patterns correlate with chemotherapy response in acute myeloid leukaemia
dc.typeArticle
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