Research

Automated detection of residual cells after sex-mismatched stem-cell transplantation – evidence for presence of disease-marker negative residual cells

Jörn Erlecke¹ , Isabell Hartmann¹ , Martin Hoffmann³ , Torsten Kroll⁴ , Heike Starke¹ , Anita Heller¹ , Alexander Gloria¹ , Herbert G Sayer⁴ , Tilman Johannes⁵ , Uwe Claussen¹ , Thomas Liehr¹ and Ivan F Loncarevic^1,2

¹  Jena University Hospital, Institute of Human Genetics and Anthropology, Kollegiengasse 10, D-07743 Jena, Germany

²  Clondiag Chip Technologies, Loebstedter Str. 103–105, 07749 Jena, Germany

³  Interdisciplinary Centre for Bioinformatics, University of Leipzig, Härtelstr. 16–18, 04107 Leipzig, Germany

⁴  Clinic of Internal Medicine II, Oncology and Hematology, University Medical Centre Jena, Erlanger Allee101, 07747 Jena, Germany

⁵  MetaSystems GmbH, Robert-Bosch-Str. 6, 68804 Altlussheim, Germany

author email corresponding author email

Molecular Cytogenetics 2009, 2:12doi:10.1186/1755-8166-2-12

Published:	29 May 2009

Abstract

Background

A new chimerism analysis based on automated interphase fluorescence in situ hybridization (FISH) evaluation was established to detect residual cells after allogene sex-mismatched bone marrow or blood stem-cell transplantation.

Cells of 58 patients were characterized as disease-associated due to presence of a bcr/abl-gene-fusion or a trisomy 8 and/or a simultaneous hybridization of gonosome-specific centromeric probes. The automatic slide scanning platform Metafer with its module MetaCyte was used to analyse 3,000 cells per sample.

Results

Overall 454 assays of 58 patients were analyzed. 13 of 58 patients showed residual recipient cells at one stage of more than 4% and 12 of 58 showed residual recipient cells less than 4%, respectively. As to be expected, patients of the latter group were associated with a higher survival rate (48 vs. 34 month). In only two of seven patients with disease-marker positive residual cells between 0.1–1.3% a relapse was observed. Besides, disease-marker negative residual cells were found in two patients without relapse at a rate of 2.8% and 3.3%, respectively.

Conclusion

The definite origin and meaning of disease-marker negative residual cells is still unclear. Overall, with the presented automatic chimerism analysis of interphase FISH slides, a sensitive method for detection of disease-marker positive residual cells is on hand.