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

Completed

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

• Registration Number: NCT01355913
• Lead Sponsor: Institut fuer anwendungsorientierte Forschung und klinische Studien GmbH

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.

Study Timeline

• Study Start: 2008-10
• Study First Submitted: 2011-05-17
• Study First Submitted QC: 2011-05-17
• Study First Posted: 2011-05-18
• Primary Completion: 2016-10
• Study Completion: 2019-10
• Status Verified: 2020-02
• Last Update Submitted: 2020-02-20
• Last Update Posted: 2020-02-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 402

Inclusion Criteria

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Screening and genetic monitoring of patients with MDS under different treatment modalities by cytogenetic analyses of circulating CD34+cells.	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.	At each timepoint of FISH analysis the percentage of aberrant interphase nuclei is measured of all (at least 200) interphase nuclei counted.

Trial Locations

Locations (13)

University Hospital Frankfurt/Main; 🇩🇪 Frankfurt/Main, Germany

University Medical Center Göttingen; 🇩🇪 Goettingen, Germany

Onkologische Kooperation Harz; 🇩🇪 Goslar, Germany

Group Practice Uhle/Müller/Kröning/Jentsch-Ullrich; 🇩🇪 Magdeburg, Germany

Onkologikum; 🇩🇪 Frankfurt/Main, Germany

Group Practice Detken/Seraphin; 🇩🇪 Northeim, Germany

Technical University Munich; 🇩🇪 Munich, Germany

Group Practice Meyer/Ammon/Müller; 🇩🇪 Göttingen, Germany

University Hospital Aachen; 🇩🇪 Aachen, Germany

University Hospital Dresden; 🇩🇪 Dresden, Germany

University Hospital Düsseldorf; 🇩🇪 Düsseldorf, Germany

Group Practice Schmidt/Galler/Klapthor; 🇩🇪 Munich, Germany

University Hospital Ulm; 🇩🇪 Ulm, Germany