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Analysis of minimal residual disease by Ig/TCR gene rearrangements: guidelines for interpretation of real-time quantitative PCR data

Abstract

Most modern treatment protocols for acute lymphoblastic leukaemia (ALL) include the analysis of minimal residual disease (MRD). To ensure comparable MRD results between different MRD-polymerase chain reaction (PCR) laboratories, standardization and quality control are essential. The European Study Group on MRD detection in ALL (ESG-MRD-ALL), consisting of 30 MRD-PCR laboratories worldwide, has developed guidelines for the interpretation of real-time quantitative PCR-based MRD data. The application of these guidelines ensures identical interpretation of MRD data between different laboratories of the same MRD-based clinical protocol. Furthermore, the ESG-MRD-ALL guidelines will facilitate the comparison of MRD data obtained in different treatment protocols, including those with new drugs.

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Acknowledgements

We thank Annemarie Wijkhuijs and Marieke Comans-Bitter for preparing the figures and to the Leukaemia Research Fund (Dr D Grant), LeukemiaNet (Professor Dr R Hehlmann) and Department of Immunology, Erasmus MC, Rotterdam, for supporting the local meeting costs of the ESG-MRD-ALL.

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Correspondence to J J M van Dongen.

Appendix

Appendix

Participants of the ESG-MRD-ALL are:

Vincent HJ van der Velden, Annemarie JM Wijkhuijs, Jacques JM van Dongen (Erasmus MC, Rotterdam, the Netherlands), C Ellen van der Schoot, Christa Homburg (Sanquin, Amsterdam, the Netherlands); Jerry Hancock, Nick Goulden (Bristol Royal Hospital for Sick Children, Bristol, Great Britain), Gill Wilson, Alice Morsman (Sheffield Children's NHS Trust, Sheffield, Great Britain), Mary Gardiner, Sandra Chudleigh (Royal Hospital for Sick Children, Glasgow, Great Britain), Paul Evans, Elizabeth Westgate (Leeds General Hospital, Leeds, Great Britain), Gary Wright, Ulrika Johansson, Margherita Corbo (St Bart's and The London School of Medicine, London, Great Britain), Letizia Foroni, Wayne Mitchell, Bella Patel (Royal Free and University College Medical School, London, Great Britain); Thomas Flohr, Claus Bartram, Rolf Koehler (University of Heidelberg, Heidelberg, Germany), Hermann Kreyenberg, Andre Willasch, Peter Bader (Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany), Cornelia Eckert, Nicola Hagedorn (Charité Medical Center CVK, Berlin, Germany), Udo zur Stadt, Elke Groh (Universitätsklinikum Eppendorf, Hamburg, Germany), Thorsten Raff, Monika Brüggemann, Michael Kneba (Universitätsklinikum Schleswig-Holstein, Kiel, Germany), Andre Schrauder, Martin Schrappe (University Hospital Schleswig-Holstein, Campus Kiel, Germany); Nathalie Grardel (Hopital Calmette, Lille Cedex, France), Elisabeth MacIntyre, Kheira Beldjord (Hôpital Necker-Enfants Malades, Paris, France), Jean-Michel Cayuela, Laurence Grollet (Hôpital Saint Louis, Paris, France), Helene Cavé, Cecile Acquaviva (Hopital Robert Debré, Paris, France); Giovanni Cazzaniga, Lillia Corral, Monica Manenti, Simona Songia, Tiziana Villa, Andrea Biondi (Universitá Milano-Bicocca, Ospedale San Gerardo, Monza, Italy), Laura del Giudice, Maddalena Paganin, Katia Polato, Giulia Fabbri, Giuseppe Basso (Dipartimento di Pediatria, Padova, Italy); Hans Madsen, Lone Schejbel (Rigshospitalet, Copenhagen, Denmark); Maria Malec-Zacharski, Anna Porwitt-MacDonald (Karolinska Sjukhuset, Stockholm, Sweden); Susanna Fischer, Ulrike Monschein, Eva Csinady, Renate Panzer-Grümayer (Children's Cancer Research Institute, St Anna Kinderspital, Vienna, Austria); Eva Fronkova, Jan Trka (2nd Medical School, Prague, Czech Republic); Marleen Bakkus, Manuela Rinaldi (Academisch Ziekenhuis – VUB, Brussels, Belgium); Rosemary Sutton, Murray Norris (Children's Cancer Institute Australia for Medical Research, Sydney, Australia); Sigal Manor, Smadar Avigad (Schneider Children's Medical Center of Israel, Petah Tikva, Israel); Beat Schäfer, Rahel Schaub (University Children's Hospital, Zurich, Switzerland); Allen Eng Juh Yeoh, Shirley Kham Kow Yin, Cecilia Sze Nga Kwok (National University of Singapore, Singapore); Ramón García Sanz, Jesus San Miguel (Hospital Universitario de Salamanca, Salamanca, Spain).

Representing the MRD laboratories of the following clinical ALL protocols:

AIEOP-BFM ALL 2000, ANZCHOG ALL Study-8, BFM-HR-ALL, DCOG-ALL10, Interfant 99, MRC-ALL 2003, MRC UKALL12, COALL 07-03, FRALLE 2000, EORTC-CLG 58951, NOPHO ALL–2000, MiniRisk (ALL-IC BFM), ALL-REZ BFM 2002, AIEOP REC 2003, MRC-UKALL R3, GMALL 07/03, GRALL 03/05 and MRC-UKALL12.

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van der Velden, V., Cazzaniga, G., Schrauder, A. et al. Analysis of minimal residual disease by Ig/TCR gene rearrangements: guidelines for interpretation of real-time quantitative PCR data. Leukemia 21, 604–611 (2007). https://doi.org/10.1038/sj.leu.2404586

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