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.