Abstract for presentation at 11th International Congress of Human Genetics

A comparison of two genetic methods for quantitative chimerism analysis after hematopoetic stem cell transplantation

  • Dr rer nat Brigitte Pabst, Institute of Human Genetics, Hannover Medical School, Germany
  • Wolfgang Kühnau, Institute of Human Genetics, Hannover Medical School, Germany
  • Christian Blumenberg, Institute of Human Genetics, Hannover Medical School, Germany
  • Christina Gerkens, Institute of Human Genetics, Hannover Medical School, Germany
  • Prof Dr med Matthias Eder, Department of Hematology, Hemostaseology and oncology, Hannover Medical School, Germany
  • PD Dr med Karl-Walter Sykora, Department of Pediatric Hematology/Oncology, Hannover Medical School, Germany
  • Prof Dr med Jörg Schmidtke, Institute of Human Genetics, Hannover Medical School, Germany

    • Chimerism testing after allogenic hematopoetic stem cell transplantation is a method used to monitor donor engraftment, graft rejection and disease relapse. This is particularly important in the context of allogeneic stem cell transplantation after reduced intensity conditioning. There are several methods used for quantification of donor cells but to date no generally accepted standard for chimerism testing is outlined. Therefore the quantification accuracy of two genetic methods was compared for analysis of posttransplant chimerism especially in respect to donor levels from 90% to 99% in a prospective analysis. All sex-mismatched samples were analysed by fluorescence-in situ-hybridization (FISH) with X and Y chromosome probe mixture on interphase cells and by in-house PCR-based multiplex amplification of fluorescent labelled short tandem repeat markers (STR).
    The analysis of two rounds of dilution experiments revealed a good correlation between FISH- and STR- analysis. The results obtained with both methods were in good agreement to each other. There was no statistical significant difference in chimerism quantification using peak area or the peak height, respectively. In a prospective study we analysed 101 samples from 32 patients with different values of donor chimerism and indications. The data obtained from both methods showed a good correlation. There were no statistically significant differences between both methods when comparing the 73 samples with a chimerism of 90% to 100% donor cells. Still in good agreement but statistically significant differences were seen in the samples with lower donor chimerism.
    Both methods show high quantification accuracy in donor chimerism greater than 90%. Because of the advantage that STR marker analysis is a sex independent method, it can be used for all patients as a method of choice.

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