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Minimal Residual Disease

Flow cytometry and IG/TCR quantitative PCR for minimal residual disease quantitation in acute lymphoblastic leukemia: a French multicenter prospective study on behalf of the FRALLE, EORTC and GRAALL

Leukemia volume 27, pages 370–376 (2013)Cite this article

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Abstract

Minimal residual disease (MRD) quantification is widely used for therapeutic stratification in pediatric acute lymphoblastic leukemia (ALL). A robust, reproducible, sensitivity of at least 0.01% has been achieved for IG/TCR clonal rearrangements using allele-specific quantitative PCR (IG/TCR-QPCR) within the EuroMRD consortium. Whether multiparameter flow cytometry (MFC) can reach such inter-center performance in ALL MRD monitoring remains unclear. In a multicenter study, MRD was measured prospectively on 598 follow-up bone marrow samples from 102 high-risk children and 136 adult ALL patients, using IG/TCR-QPCR and 4/5 color MFC. At diagnosis, all 238 patients (100%) had at least one suitable MRD marker with 0.01% sensitivity, including 205/238 samples (86%) by using IG/TCR-QPCR and 223/238 samples (94%) by using MFC. QPCR and MFC were evaluable in 495/598 (83%) samples. Qualitative results (<0.01% or ⩾0.01%) concurred in 96% of samples and overall positivity (including <0.01% and nonquantifiable positivity) was concurrent in 84%. MRD values ⩾0.01% correlated highly (r2=0.87) and 69% clustered within half-a-log10. QPCR and MFC can therefore be comparable if properly standardized, and are highly complementary. MFC strategies will benefit from a concerted approach, as does molecular MRD monitoring, and will contribute significantly to the achievement of 100% MRD informativity in adult and pediatric ALL.

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Acknowledgements

This work was supported by a grant ‘Soutien aux Techniques Innovantes et Coûteuses’ (STIC) by the French Institut National du Cancer (InCA) and benefited from support by the companies BD Biosciences and Beckman Coulter. We are grateful to all clinicians, biologists and clinical research assistants involved in the FRALLE, EORTC and GRAALL clinical trials, where the patients were enrolled. Special thanks are addressed to Véronique Lhéritier for her great help with the adult patients’database.

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  1. R Garand, K Beldjord, H Cavé and C Fossat: These authors contributed equally to this work.

Authors and Affiliations

  1. CHU Nantes, Nantes, France

    R Garand & N Robillard

  2. APHP-Hôpital Saint Louis, Paris, France

    K Beldjord & H Dombret

  3. APHP-Hôpital Robert-Debré, Paris, France

    H Cavé, E Clappier & A Baruchel

  4. Hôpital de la Timone, Marseille, France

    C Fossat & I Arnoux

  5. Department of Hematology, APHP-Hôpital Necker, Paris, France

    K Beldjord, V Asnafi, C Brouzes & E Macintyre

  6. IHOP, Lyon, France

    Y Bertrand

  7. CHU Rennes, Rennes, France

    M-L Boulland, T Fest & M Roussel

  8. CHU Toulouse, Toulouse, France

    E Delabesse, F Huguet, E Kuhlein & J Tkaczuk

  9. CHU Besançon, Besançon, France

    F Garnache-Ottou

  10. CHU Grenoble, Grenoble, France

    M-C Jacob

  11. CHU Montpellier, Montpellier, France

    S Marty-Grès

  12. Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon, France

    A Plesa

  13. CHU Angers, Angers, France

    N Ifrah

  14. Immunology Laboratory, Université de Lorraine & CHU Nancy, Nancy, France

    M C Béné

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Correspondence to E Macintyre or M C Béné.

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Garand, R., Beldjord, K., Cavé, H. et al. Flow cytometry and IG/TCR quantitative PCR for minimal residual disease quantitation in acute lymphoblastic leukemia: a French multicenter prospective study on behalf of the FRALLE, EORTC and GRAALL. Leukemia 27, 370–376 (2013). https://doi.org/10.1038/leu.2012.234

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