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Minimal Residual Disease

Monitoring of WT1 expression in PB and CD34+ donor chimerism of BM predicts early relapse in AML and MDS patients after hematopoietic cell transplantation with reduced-intensity conditioning

Leukemia volume 25, pages 498–505 (2011)Cite this article

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Abstract

Relapse of malignant disease remains the major complication in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) after hematopoietic cell transplantation (HCT) with reduced-intensity conditioning (RIC). In this study, we investigated the predictive value of disease-specific markers (DSMs), donor chimerism (DC) analysis of unsorted (UDC) or CD34+ sorted cells and Wilms’ tumor gene 1 (WT1) expression. Eighty-eight patients with AML or MDS were monitored after allogenic HCT following 2 Gy total-body irradiation with (n=84) or without (n=4) fludarabine 3 × 30 mg/m2, followed by cyclosporin A and mycophenolate mofetil. DSMs were determined by fluorescence in situ hybridization (FISH) and WT1 expression by real-time polymerase chain reaction. Chimerism analysis was performed on unsorted or CD34+ sorted cells, by FISH or short tandem repeat polymerase chain reaction. Twenty-one (24%) patients relapsed within 4 months after HCT. UDC, CD34+ DC and WT1 expression were each significant predictors of relapse with sensitivities ranging from 53 to 79% and specificities of 82–91%. Relapse within 28 days was excluded almost entirely on the basis of WT1 expression combined with CD34+ DC kinetics. Monitoring of WT1 expression and CD34+ DC predict relapse of AML and MDS after RIC-HCT.

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Acknowledgements

We thank Janet Bogardt, Dagmar Crohn, Christa Döring, Christina Franke, Christine Günther, Evelyn Hennig, Ines Kovacs, Rainer Krahl, Christel Müller and Scarlet Musiol for their excellent assistance.

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  1. T Lange and M Hubmann: These two authors contributed equally to this work.

Authors and Affiliations

  1. Department of Hematology, Oncology and Hemostaseology, University of Leipzig, Leipzig, Germany

    T Lange, M Hubmann, G-N Franke, M Cross, S Leiblein, H K Al-Ali & D Niederwieser

  2. Department of Clinical Chemistry and Molecular Diagnostics, University of Leipzig, Leipzig, Germany

    R Burkhardt & J Thiery

  3. Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany

    M Scholz

  4. Department for Forensic Medicine at the University of Leipzig, Leipzig, Germany

    J Edelmann

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Lange, T., Hubmann, M., Burkhardt, R. et al. Monitoring of WT1 expression in PB and CD34+ donor chimerism of BM predicts early relapse in AML and MDS patients after hematopoietic cell transplantation with reduced-intensity conditioning. Leukemia 25, 498–505 (2011). https://doi.org/10.1038/leu.2010.283

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