Screening and Genetic Monitoring of Patients With MDS Under Different Treatment Modalities by Cytogenetic Analyses of Circulating CD34+Cells
Chromosomal aberrations in myelodysplastic syndromes (MDS) play a major role in diagnostics,
pathogenesis, prognosis, and, more recently, in treatment allocations. Chromosomal anomalies
can be detected by conventional chromosome banding analyses of bone marrow metaphases and
most of them are provable by Fluorescence in situ hybridization (FISH) of circulating CD34+
progenitor cells from peripheral blood. For this prospective multicenter non-interventional
diagnostic study sequential FISH analyses are performed on immunomagnetically enriched
circulating CD34+ cells from peripheral blood as follows: A "super-panel" with the probes
D7/CEP7, EGR1, CEP8, CEP XY, D20, p53, IGH/BCL2, TEL/AML1, RB1, MLL, 1p36/1q25, CSF1R (all
Abbott® probes) is used for initial screening, every 12 months during follow-up and in every
case of suspected progression. A smaller "standard-panel" with the probes EGR1, D7/CEP7,
CEP8, p53, D20, CEP X/Y, TEL/AML1 - plus if necessary an informative probe of the
superpanel- was performed for analyses at short intervals every 2 months in the 1st year and
every 3 months during the 2nd and 3rd year. Peripheral blood counts are documented once a
month, and full blood counts with the number of peripheral blasts are recommended at the
time point of each FISH analysis. Bone marrow biopsies are not part of the study, but they
are recommended to be performed every 6 to 12 months in the course of the disease. If a bone
marrow biopsy is performed, conventional chromosome banding analyses on bone marrow
metaphases and, additionally, FISH analyses of enriched CD34+ bone marrow cells and
non-enriched bone marrow cells are performed. The results from peripheral blood are
correlated with those of conventional banding and FISH analyses performed on bone marrow
samples. The aims of this study are to detect acqired chromosomal aberrations in MDS
patients from peripheral blood, to follow these anomalies by frequent analyses, to detect
rare aberrations and to observe karyotype evolution from peripheral blood.
Observational Model: Case-Only, Time Perspective: Prospective
Screening and genetic monitoring of patients with MDS under different treatment modalities by cytogenetic analyses of circulating CD34+cells.
At each timepoint of FISH analysis the percentage of aberrant interphase nuclei is measured of all (at least 200) interphase nuclei counted.
The first FISH analysis is performed at the time of study entry (initial screening) and after that every 2 months in the first year and every 3 months in the second and third year.
Detlef Haase, MD, Prof.
University Medical Center Göttingen
Germany: Ethics Commission