Screening and Genetic Monitoring of Patients With Myelodysplastic Syndromes (MDS) Under Different Treatment Modalities by Cytogenetic Analyses of Circulating CD34+Cells

NCT ID: NCT01355913

Last Updated: 2020-02-21

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 402 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2008-10-31
• Study Completion Date: 2019-10-31

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.

Conditions

Myelodysplastic Syndromes (MDS); Chromosmal Aberrations; Karyotype Evolution; Rare Abnormalities; Cytogenetic Monitoring

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Medical Center Goettingen

OTHER

Sponsor Role: collaborator

Institut fuer anwendungsorientierte Forschung und klinische Studien GmbH

OTHER

Sponsor Role: lead

Responsible Party

University Medical Center Goettingen

Principal Investigators

Detlef Haase, MD, Prof.

Role: STUDY_CHAIR

University Medical Center Göttingen

Locations

University Hospital Aachen

Aachen, , Germany

University Hospital Dresden

Dresden, , Germany

University Hospital Düsseldorf

Düsseldorf, , Germany

Onkologikum

Frankfurt am Main, , Germany

University Hospital Frankfurt/Main

Frankfurt am Main, , Germany

Onkologische Kooperation Harz

Goslar, , Germany

Group Practice Meyer/Ammon/Müller

Göttingen, , Germany

University Medical Center Göttingen

Göttingen, , Germany

Group Practice Uhle/Müller/Kröning/Jentsch-Ullrich

Magdeburg, , Germany

Group Practice Schmidt/Galler/Klapthor

Munich, , Germany

Technical University Munich

Munich, , Germany

Group Practice Detken/Seraphin

Northeim, , Germany

University Hospital Ulm

Ulm, , Germany

Countries

Germany

References

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.

Reference Type: DERIVED

PMID: 26355708 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25344522 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 23623559 (View on PubMed)

Other Identifiers

Diagnostik-Studie

Identifier Type: -

Identifier Source: org_study_id