Clinical trial NCT01355913: Screening and Genetic Monitoring of Patients With Myelodysplastic Syndromes (MDS) Under Different Treatment Modalities by Cytogenetic Analyses of Circulating CD34+Cells
Official title: Screening and Genetic Monitoring of Patients With MDS Under Different Treatment Modalities by Cytogenetic Analyses of Circulating CD34+Cells
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Myelodysplastic Syndromes (MDS)
Chromosmal Aberrations
Karyotype Evolution
Rare Abnormalities
Cytogenetic Monitoring
Keywords: Myelodysplastic syndromes (MDS)
chromosmal aberrations
cytogenetics
Fluorescence in situ hybridization (FISH)
CD34+ cells
peripheral blood
Lead sponsor: Institut fuer anwendungsorientierte Forschung und klinische Studien GmbH
Sponsor class: OTHER
Collaborators: name: University Medical Center Goettingen
First posted: 2011-05-18
Enrollment: 402
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: 20 ml of peripheral blood (pb) of a MDS patient are enriched by immunomagnetic cell sorting (by MACS® system). A FISH analysis is performed on these CD34+ cells according to product protocols using the FISH probe panels described above. The percentage of aberrant interphase nuclei (IN) is measured related to all (at least 200) IN counted. FISH analyses are performed every 2 months in the 1st and every 3 months in the 2nd and 3rd year of follow-up by the same method using the standard panel and, if necessary, an informative probe of the super panel. Pb counts are documented once a month, and full blood counts with peripheral blasts are recommended at the time point of each FISH analysis. Bone marrow (bm) biopsies are not part of the study, but they are recommended to be performed every 6 to 12 months. If a bm biopsy is performed, conventional chromosome banding analyses on bm metaphases and FISH analyses of enriched CD34+ and non-enriched bm cells are performed.

Brief summary: In myelodysplastic syndromes (MDS) the knowledge about chromosomal aberrations is important for diagnosis, pathogenesis, prognosis and treatment. Usually, chromosomal anomalies in MDS patients are detected in bone marrow cells by chromosome banding analyses of metaphases. Alternatively or additionally they can be diagnosed by Fluorescence-in-Situ-Hybridization (FISH). The investigators here present a novel method for cytogenetic monitoring of MDS patients from peripheral blood which is representative for the clone size in bone marrow cells. The purpose of this prospective multicenter non-interventional diagnostic study is to detect and to follow chromosomal aberrations from peripheral blood closely, to assess karyotype evolution, to detect rare abnormalities and to correlate the molecular-cytogenetic results with peripheral blood counts, bone marrow morphology and treatment modalities and responses.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Clinical diagnosis (cytomorphologic proof) of primary or secondary myelodysplastic syndrome (MDS) or
* Suspected myelodysplastic syndrome (MDS).
* Age \> 18 years

Primary outcomes:
measure: Screening and genetic monitoring of patients with MDS under different treatment modalities by cytogenetic analyses of circulating CD34+cells.
timeFrame: 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.
Secondary outcomes:
Other outcomes:
Locations:
city: Aachen
country: Germany
facility: University Hospital Aachen
city: Dresden
country: Germany
facility: University Hospital Dresden
city: Düsseldorf
country: Germany
facility: University Hospital Düsseldorf
city: Frankfurt/Main
country: Germany
facility: Onkologikum
city: Frankfurt/Main
country: Germany
facility: University Hospital Frankfurt/Main
city: Goettingen
country: Germany
facility: University Medical Center Göttingen
city: Goslar
country: Germany
facility: Onkologische Kooperation Harz
city: Göttingen
country: Germany
facility: Group Practice Meyer/Ammon/Müller
city: Magdeburg
country: Germany
facility: Group Practice Uhle/Müller/Kröning/Jentsch-Ullrich
city: Munich
country: Germany
facility: Group Practice Schmidt/Galler/Klapthor
city: Munich
country: Germany
facility: Technical University Munich
city: Northeim
country: Germany
facility: Group Practice Detken/Seraphin
city: Ulm
country: Germany
facility: University Hospital Ulm
Study officials:
affiliation: University Medical Center Göttingen
name: Detlef Haase, MD, Prof.
role: STUDY_CHAIR
References:
citation: Braulke F, Muller-Thomas C, Gotze K, Platzbecker U, Germing U, Hofmann WK, Giagounidis AA, Lubbert M, Greenberg PL, Bennett JM, Sole F, Slovak ML, Ohyashiki K, Le Beau MM, Tuchler H, Pfeilstocker M, Hildebrandt B, Aul C, Stauder R, Valent P, Fonatsch C, Bacher U, Trumper L, Haase D, Schanz J. Frequency of del(12p) is commonly underestimated in myelodysplastic syndromes: Results from a German diagnostic study in comparison with an international control group. Genes Chromosomes Cancer. 2015 Dec;54(12):809-17. doi: 10.1002/gcc.22292. Epub 2015 Sep 10.
citation: Braulke F, Platzbecker U, Muller-Thomas C, Gotze K, Germing U, Brummendorf TH, Nolte F, Hofmann WK, Giagounidis AA, Lubbert M, Greenberg PL, Bennett JM, Sole F, Mallo M, Slovak ML, Ohyashiki K, Le Beau MM, Tuchler H, Pfeilstocker M, Nosslinger T, Hildebrandt B, Shirneshan K, Aul C, Stauder R, Sperr WR, Valent P, Fonatsch C, Trumper L, Haase D, Schanz J. Validation of cytogenetic risk groups according to International Prognostic Scoring Systems by peripheral blood CD34+FISH: results from a German diagnostic study in comparison with an international control group. Haematologica. 2015 Feb;100(2):205-13. doi: 10.3324/haematol.2014.110452. Epub 2014 Oct 24.
citation: Braulke F, Jung K, Schanz J, Gotze K, Muller-Thomas C, Platzbecker U, Germing U, Brummendorf TH, Bug G, Ottmann O, Giagounidis AA, Stadler M, Hofmann WK, Schafhausen P, Lubbert M, Schlenk RF, Blau IW, Ganster C, Pfeiffer S, Shirneshan K, Metz M, Detken S, Seraphin J, Jentsch-Ullrich K, Bohme A, Schmidt B, Trumper L, Haase D. Molecular cytogenetic monitoring from CD34+ peripheral blood cells in myelodysplastic syndromes: first results from a prospective multicenter German diagnostic study. Leuk Res. 2013 Aug;37(8):900-6. doi: 10.1016/j.leukres.2013.03.019. Epub 2013 Apr 25.