ALBERT

Description: INTRODUCTION: Myelodysplastic syndromes are dynamic diseases affecting the stem cell compartment in bone marrow presenting with different clinical courses ranging from stable, indolent disease to rapid progression to acute myeloid leukemias. So far, only 3 studies on karyotype analysis in MDS with a minimum of 30 patients have been published. Most knowledge about genetic evolution in MDS is based on the description of parallely existing subclones within one single examination. Thus, little is known about the real frequency, the time spans and the clinical impact of karyotype evolution. MATERIALS AND METHODS: So far, data from 322 patients with MDS or secondary AML and at least two successfully performed classical cytogenetic analyses are available from four centres of the Competence Network Acute and Chronic Leukemias. As yet, we retrospectively examined 268 patients out of this data set. Karyotype evolution (KE) was defined as acquisition of additional aberrations, expansion of an aberrant clone (〉20%) or development of a completely aberrant karyotype after an initial mosaic karyotype. RESULTS: In 44 cases (16%) KE was observed. In the mean 2.8 (range 2–9) cytogenetic examinations have been performed. In 27 cases additional aberrations occurred and in 17 cases the abnormal clone expanded in a subsequent analysis. Compared to stable courses, patients with KE had a tendency towards a shorter survival (p=0.15). In the group of patients with expansion of the aberrant clone the most frequent karyotypes were −7/7q- (4x), complex (3x), 5q- (3x) and +8 (3x). The most frequent karyotypes in which during the course of the disease additional aberrations occurred were complex (4x) and karyotypes with two miscellaneous aberrations (4x). The most frequent additional aberrations were 5q- (3x) and −17/17p- (3x). CONCLUSIONS: In sequential cytogenetic examinations KE is a frequent event. Patients with KE tend to have a shortened survival. In our collective no long-term survivor could be observed in the group displaying KE regardless of the therapy strategies (excluding allogeneic transplantation). In this multicentric study which encompasses the largest data base on sequential analyses in MDS to date, frequency, evolution patterns and prognostic relevance of karyotype changes have been studied allowing a better insight into the genetic dynamics of MDS.

Description: Myelodysplastic syndromes are dynamic diseases presenting with different clinical courses ranging from almost stable courses to rapid progression to acute myeloid leukemias. Karyotype is one of the most important prognostic factors and defines subgroups of favorable, intermediate and adverse prognosis. So far, comparably low attention has been payed on karyotypic changes occuring in sequential cytogentic examinations during the course of the disease. We retrospectively examined karyotypes of 577 patients with MDS or AML with previous history of MDS and at least two successfully performed metaphase analyses. The cytogenetic and clinical data was collected from 5 different centres of the “Kompetenznetz Akute und Chronische Leukaemien” (Duesseldorf, Duisburg, Freiburg, Goettingen, Vienna). Compared to the inital karyotype, karyotype evolution was defined as acquisition of additional aberrations, expansion of an aberrant clone by more than 20% or development of a completely aberrant karyotype after a former mosaic karyotype. According to these criteria, we found karyotype evolution in 155 cases (27%). 2–8 cytogenetic examinations have been performed per case. In 121 cases additional aberrations occured and in 34 cases the aberrant clone expanded in a subsequent analysis. In the group of patients with expansion of the aberrant clone the most frequent karyotypes were 5q- (9x) and +8 (7x). The most frequent aberrant karyotypes later acquiring additional aberrations were complex (22x) and karyotypes with two aberrations (11x), but in the vast majority of cases additional aberrations occurred on basis of a normal karyotype (70x). The most frequent additional aberrations were −7/7q- (23x), 5q- (11x) and +8 (11x). In the group of initially normal karyotypes patients with karyotype evolution had a shorter survivial (p