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dc.contributor.advisor Haase, Detlef Prof. Dr.
dc.contributor.author Cevik, Naciye
dc.date.accessioned 2016-03-10T10:32:24Z
dc.date.available 2016-03-30T22:50:05Z
dc.date.issued 2016-03-10
dc.identifier.uri http://hdl.handle.net/11858/00-1735-0000-0028-86F8-0
dc.language.iso deu de
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.ddc 610 de
dc.title Klonale Evolution und zytogenetische Evolutionsmuster bei Myelodysplastischen Syndromen (MDS) und sekundärer akuter myeloischer Leukämie nach MDS de
dc.type doctoralThesis de
dc.title.translated Clonal evolution and evolution patterns of myelodysplastic syndroms and acute leukemia following MDS de
dc.contributor.referee Pauli, Silke PD Dr.
dc.date.examination 2016-03-23
dc.description.abstracteng Myelodysplastic syndromes (MDS) are clonal stem cell disorders characterized by heterogeneous symptoms and disease progression based on a multistep pathogenesis. Genetic instability promotes the gradual or sudden accumulation of genetic aberrations and thus, the development of clonal evolution reflecting the progression of disease (Haase 2005). The objective of the present study was to describe evolution patterns and to assess the prognostic value of clonal evolution and its different patterns for the clinical course of patients with MDS and acute leukemia following MDS. Retrospectively, data from 729 patients and 225 follow-up examinations with a total of 1208 chromosome analyses were evaluated. The results indicate that clonal evolution is associated with a poor prognosis. In patients with clonal evolution the median survival was significantly shorter (24.4 months vs. 103.6 months, p<0.01) and transition to AML more frequent (48.0% vs. 21.4%, p<0.01) than in those without. In addition, clonal evolution was associated with a significantly more rapid transition to acute myeloid leukaemia (AML) (17.5 months vs. n.e., p<0.01). Clonal evolution was subdivided into an early and a late type depending on its time of onset (median: after 5.3 months vs. 21.9 months; p<0.01). The time of onset of clonal evolution and its diagnosis were additional prognostic factors. Detection of clonal evolution already at initial diagnosis was associated with a poor overall survival (8.2 months vs. 32.6 months, p<0.01). In patients with clonal evolution, the prognosis was influenced by the clonal composition allowing differentiation of further clinical subgroups. Increase of clone size (6.6 months vs. 18.0 months, p=0.046) and occurrence of additional aberrations over time (6.6 months vs. 19.5 months, p=0.022) were associated with a poor prognosis. The evolution patterns described by Tricot et al. (1985), which are primarily based on the rate of blast cells, were extended by the cytogenetic data resulting into the differentiation of five main groups. Based on the primary and follow-up data, different patterns of disease evolution were identified and assigned to specific chromosomal abnormalities. Among patients with clonal evolution, the index aberrations monosomy 7/7q deletion (8.2 months vs. 18.2 months, p=0.020) and 17p anomalies (1.8 months vs. 17.9 months, p=0.002) were associated with a poor prognosis. In those with clonal evolution, frequent anomalies were the 5q deletion and 17p anomalies. In previously published prognostic scoring systems, clonal evolution and its different patterns had not been incorporated. Information on disease progression and clonal evolution patterns as detected by sequential cytogenetic analyses enable a therapy adjusted to the course of the disease. This study indicates that clonal evolution and its different patterns are important prognostic factors in MDS and acute leukemia following MDS. In the future, scoring systems should consider these factors to enable a more accurate individual risk assessment. de
dc.contributor.coReferee Schön, Margarete Prof. Dr.
dc.subject.eng Myelodysplastic syndromes (MDS) de
dc.subject.eng clonal evolution de
dc.subject.eng clonal evolution patterns de
dc.identifier.urn urn:nbn:de:gbv:7-11858/00-1735-0000-0028-86F8-0-3
dc.affiliation.institute Medizinische Fakultät de
dc.subject.gokfull Medizin (PPN619874732) de
dc.subject.gokfull GOK-MEDIZIN de
dc.description.embargoed 2016-03-30
dc.identifier.ppn 850947510

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