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Detection of relapse after hematopoietic stem cell transplantation in childhood by monitoring of WT1 expression and chimerism

  • Original Article – Clinical Oncology
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Abstract

Purpose

The measurement of minimal residual disease after hematopoietic stem cell transplantation is crucial for the prevention of hematological relapses. But many methods are limited to certain groups of patients. We present a comparison of two markers which are universally applicable: WT1 expression and chimerism status.

Methods

We analyzed 1,848 peripheral blood and bone marrow samples of 148 children, adolescents and young adults with malignant hematological diseases. Median follow-up time was 739 days after transplantation.

Results

All patients suffering from hematological relapse showed high WT1 levels. Approximately half (51 %) of the 37 relapses could have been detected early through an increase in WT1 expression. WT1 kinetics revealed to be more specific than single elevated WT1 levels (p < 0.05) and chimerism analysis (p < 0.05). Combined with chimerism analysis, 74 % of relapses were detectable in advance. Elevated WT1 expression levels after transplantation reached the highest sensitivity (64.9 %) as a single marker, although differences were not significant. When the dynamics of both markers as well as any elevated WT1 expression were taken into account, a sensitivity of 81.5 % and a specificity of 83.7 % were obtained.

Conclusions

Hence, we conclude that WT1 is a useful marker for monitoring of minimal residual disease after transplantation, if specific targets are not available. WT1 expression and chimerism status should be mutually evaluated to decide about immunotherapeutic interventions aimed at preventing morphological relapse.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standards

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008. Informed consent was obtained from all patients for being included in the study.

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Authors and Affiliations

  1. Department of Pediatrics, Jena University Hospital, Kochstr. 2, 07745, Jena, Germany

    Caroline Woehlecke, Susan Wittig & Bernd Gruhn

  2. Institute for Forensic Medicine, Jena University Hospital, Jena, Germany

    Juliane Sanft

  3. Division for Stem Cell Transplantation and Immunology, Department for Children and Adolescents, University Hospital, Goethe University, Frankfurt am Main, Germany

    Hermann Kreyenberg

Authors
  1. Caroline Woehlecke
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  2. Susan Wittig
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  3. Juliane Sanft
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  4. Hermann Kreyenberg
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  5. Bernd Gruhn
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Corresponding author

Correspondence to Bernd Gruhn.

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Woehlecke, C., Wittig, S., Sanft, J. et al. Detection of relapse after hematopoietic stem cell transplantation in childhood by monitoring of WT1 expression and chimerism. J Cancer Res Clin Oncol 141, 1283–1290 (2015). https://doi.org/10.1007/s00432-015-1919-0

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  • DOI: https://doi.org/10.1007/s00432-015-1919-0

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