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Chronic Lymphocytic Leukemia

The EuroChimerism concept for a standardized approach to chimerism analysis after allogeneic stem cell transplantation

Leukemia volume 26, pages 1821–1828 (2012)Cite this article

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Abstract

Hematopoietic stem cell transplantation is becoming an increasingly important approach to treatment of different malignant and non-malignant disorders. There is thus growing demand for diagnostic assays permitting the surveillance of donor/recipient chimerism posttransplant. Current techniques are heterogeneous, rendering uniform evaluation and comparison of diagnostic results between centers difficult. Leading laboratories from 10 European countries have therefore performed a collaborative study supported by a European grant, the EuroChimerism Concerted Action, with the aim to develop a standardized diagnostic methodology for the detection and monitoring of chimerism in patients undergoing allogeneic stem cell transplantation. Following extensive analysis of a large set of microsatellite/short tandem repeat (STR) loci, the EuroChimerism (EUC) panel comprising 13 STR markers was established with the aim to optimally meet the specific requirements of quantitative chimerism analysis. Based on highly stringent selection criteria, the EUC panel provides multiple informative markers in any transplant setting. The standardized STR-PCR tests permit detection of donor- or recipient-derived cells at a sensitivity ranging between 0.8 and 1.6%. Moreover, the EUC assay facilitates accurate and reproducible quantification of donor and recipient hematopoietic cells. Wide use of the European-harmonized protocol for chimerism analysis presented will provide a basis for optimal diagnostic support and timely treatment decisions.

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Acknowledgements

We are grateful to the EU officers who have supervised and supported the project, including particularly Jaime Renart, Cornelius Schmaltz, Maria-José Vidal-Ragout and Micheline Divaris-Lambert. Moreover, we greatly appreciate the financial administrative help of Claudia Hochweis, Stefan Grünert, Alexandra Lidy and Karla Valdés-Rodriguez, the secretarial support of Ingrid Kerschberger and Nicole Reisinger at the coordinating center (CCRI) and the contributions of numerous technicians at the participating centers. The EuroChimerism Concerted Action (full project title: Diagnostic approaches to chimerism testing after allogeneic stem cell transplantation for early detection of graft rejection and relapse: technical development, standardization and European-coordinated clinical implementation) was carried out with financial support from the European commission within the call Quality of Life and Management of Living Resources, Fifth Framework Program, project No QLG1-CT-2002-01485.

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Authors and Affiliations

  1. Children's Cancer Research Institute and Department of Pediatrics, Meduniwien, Vienna, Austria

    T Lion, F Watzinger & S Preuner

  2. Department of Pediatrics, University Frankfurt, Frankfurt, Germany

    H Kreyenberg & P Bader

  3. Department Transplantation Immunology Maastricht University, Maastricht, The Netherlands

    M Tilanus

  4. Department of Pathology University Medical Center, Utrecht, The Netherlands

    R de Weger, J van Loon & L de Vries

  5. Hopital Robert Debré, Paris, France

    H Cavé & C Acquaviva

  6. St James Hospital, Dublin, Ireland

    M Lawler & M Crampe

  7. Department of Clinical and Biological Sciences, University Turin, Turin, Italy

    A Serra & B Saglio

  8. Department of Pediatrics, University Milano, Monza, Italy

    F Colnaghi & A Biondi

  9. Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

    J J M van Dongen & M van der Burg

  10. Department of Hematology, University Salamanca, Salamanca, Spain

    M Gonzalez & M Alcoceba

  11. Clinical Genetics, University Hospital, Uppsala, Sweden

    G Barbany & M Hermanson

  12. Department of Internal Medicine, University Hospitals and University of Geneva, Geneva, Switzerland

    E Roosnek

  13. Royal Hospital for Children, Bristol, UK

    C Steward

  14. H&I Laboratory, National Blood and Transplant Service, Bristol, UK

    J Harvey

  15. Department of Medical Statistics, CEMSIIS, Medical University Vienna, Vienna, Austria,

    F Frommlet

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  1. T Lion
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  17. J J M van Dongen
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  18. M van der Burg
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  19. M Gonzalez
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  20. M Alcoceba
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Consortia

on behalf of the EuroChimerism Consortium (EU-Project number: QLG1-CT-2002-01485)

Corresponding author

Correspondence to T Lion.

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Competing interests

The EUC marker panel has been filed for patenting (A948/2006; PCT/AT2007/000266; EP2 024 508-2009) and the IP rights were assigned to the EuroChimerism consortium by an official document (Consortial Agreement). The IP rights were subsequently obtained by the industrial partner of the EuroChimerism consortium, Milenyi Biotec, Bergisch Gladbach, Germany. Revenues resulting from the recently launched kit based on the EUC panel must be used for further activities of the EuroChimerism Consortium in line with regulations specified in the Consortial Agreement.

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Supplementary Information accompanies the paper on the Leukemia website

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Lion, T., Watzinger, F., Preuner, S. et al. The EuroChimerism concept for a standardized approach to chimerism analysis after allogeneic stem cell transplantation. Leukemia 26, 1821–1828 (2012). https://doi.org/10.1038/leu.2012.66

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