Acute myeloid leukaemia in the elderly: Clinical management and the application of molecular cytogenetic techniques
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In Western Europe and North America, acute myeloid leukaemia (AML) is
predominantly a disease of the elderly, with a median age at the time of
presentation in excess of 60 years. However, many clinical trials in AML fail to
recruit elderly adults due to a combination of strict entry criteria, or physician or
patient bias. Thus, clinical outcome data from many trials may not be readily
applicable to older patients with the disease. Furthermore, because the clinical
outcome for many older patients with AML is frequently poor, elderly patients
who receive intensive chemotherapy with curative intent are frequently selected
for treatment on clinical criteria rather than on objective prognostic criteria that
may define clinical outcome.
The karyotype at the time of presentation may be considered one of the most
important prognostic factors in adult AML. Therefore, the aim of this thesis were
firstly to analyse the clinical outcome data from a cohort of elderly patients
managed at a single centre in order to document the cytogenetic features of AML
in an elderly population, to define the prognostic importance of presentation
karyotype in the elderly, and to identify other prognostic factors. Retrospective
analysis clearly demonstrated improved clinical outcome for older patients with
AML over time, primarily as a consequence of improved supportive care and the
delivery of more intensive chemotherapy. In addition, 'unfavourable'
presentation karyotype, increasing age and raised serum LDH were found to
correlate with poor clinical outcome
Molecular cytogenetic techniques based upon fluorescence in-situ hybridisation
technology offer the chance to detect and analyse cytogenetic aberrations at a
higher resolution than can be achieved with conventional techniques. The
cytogenetic data provided by comparative genomic hybridisation and mulitplex
fluorescence in-situ hybridisation when used in the analysis of elderly patients
with AML were found to correlate well with results obtained by conventional
methods. Importantly, additive cytogenetic data were more likely to be provided
if multiplex-fluorescence in-situ hybridisation was used in the analysis of cases
with marker chromosomes or in cases with complex karyotype, although the
technique was limited by an inability to reliably detect telomeric translocations.
In addition, although both techniques can be used to complement conventional
G-banding analysis, conventional FISH methods are often required to confirm
the results.
Authors
Dalley, Christopher DeanCollections
- Theses [4116]