Standardization of flow cytometric minimal residual disease evaluation in acute lymphoblastic leukemia: Multicentric assessment is feasible

Authors

  • Michael Norbert Dworzak,

    Corresponding author
    1. Children's Cancer Research Institute and St. Anna Children's Hospital, Vienna, Austria
    • Children's Cancer Research Institute (CCRI), Department of Pediatric Hematology and Oncology, St. Anna Kinderspital, Kinderspitalgasse 6, A-1090 Vienna, Austria
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    • Giuseppe Gaipa, Marinella Veltroni, Michael Norbert Dworzak, and Richard Ratei contributed equally to this work.

  • Giuseppe Gaipa,

    1. Tettamanti Research Center, Department of Pediatrics, University of Milano-Bicocca, Ospedale San Gerardo, Monza, Italy
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    • Giuseppe Gaipa, Marinella Veltroni, Michael Norbert Dworzak, and Richard Ratei contributed equally to this work.

  • Richard Ratei,

    1. Department of Hematology, Oncology and Tumor Immunology, Robert-Roessle-Clinic at the HELIOS Klinikum Berlin, Charité Medical School, Berlin, Germany
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    • Giuseppe Gaipa, Marinella Veltroni, Michael Norbert Dworzak, and Richard Ratei contributed equally to this work.

  • Marinella Veltroni,

    1. Laboratory of Pediatric Onco-Hematology, Department of Pediatrics, University Hospital of Padova, Padova, Italy
    2. Department of Pediatrics, University of Florence, Florence, Italy
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    • Giuseppe Gaipa, Marinella Veltroni, Michael Norbert Dworzak, and Richard Ratei contributed equally to this work.

  • Angela Schumich,

    1. Children's Cancer Research Institute and St. Anna Children's Hospital, Vienna, Austria
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  • Oscar Maglia,

    1. Tettamanti Research Center, Department of Pediatrics, University of Milano-Bicocca, Ospedale San Gerardo, Monza, Italy
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  • Leonid Karawajew,

    1. Department of Hematology, Oncology and Tumor Immunology, Robert-Roessle-Clinic at the HELIOS Klinikum Berlin, Charité Medical School, Berlin, Germany
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  • Allessandra Benetello,

    1. Laboratory of Pediatric Onco-Hematology, Department of Pediatrics, University Hospital of Padova, Padova, Italy
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  • Ulrike Pötschger,

    1. Children's Cancer Research Institute and St. Anna Children's Hospital, Vienna, Austria
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  • Zvenyslava Husak,

    1. Children's Cancer Research Institute and St. Anna Children's Hospital, Vienna, Austria
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  • Helmut Gadner,

    1. Children's Cancer Research Institute and St. Anna Children's Hospital, Vienna, Austria
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  • Andrea Biondi,

    1. Tettamanti Research Center, Department of Pediatrics, University of Milano-Bicocca, Ospedale San Gerardo, Monza, Italy
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  • Wolf-Dieter Ludwig,

    1. Department of Hematology, Oncology and Tumor Immunology, Robert-Roessle-Clinic at the HELIOS Klinikum Berlin, Charité Medical School, Berlin, Germany
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  • Giuseppe Basso

    1. Laboratory of Pediatric Onco-Hematology, Department of Pediatrics, University Hospital of Padova, Padova, Italy
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  • The data given in this work are the results of the AIEOP-BFM-ALL-FCM-MRD-Study Group.

  • How to cite this article: Dworzak MN, Gaipa G, Ratei R, Veltroni M, Schumich A, Maglia O, Karawajew L, Benetello A, Potschger U, Husak Z, Gadner H, Biondi A, Ludwig W-D, Basso G. Standardization of flow cytometric minimal residual disease evaluation in acute lymphoblastic leukemia: multicentric assessment is feasible. Cytometry Part B 2008; 74B: 331–340.

Abstract

Background:

Single-laboratory experience showed that flow cytometric (FCM) assessment of minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL) is feasible in most patients and gives independent prognostic information. It is, however, not known whether FCM analysis can reliably be standardized for multicentric application.

Methods:

An extensive standardization program was installed in four collaborating laboratories, which study FCM-MRD in children treated with the AIEOP-BFM-ALL 2000 protocol. This included methodological alignment, continuous quality monitoring, as well as personnel education by exchange and performance feed-back.

Results:

Blinded inter-laboratory tests of list-mode data interpretation concordance (n = 202 blood and bone marrow samples from follow-up during induction of 31 randomly selected patients of a total series of n = 395) showed a very high degree of inter-rater agreement among the four centers despite differences in cytometers and software usage (intraclass correlation coefficient [ICC] 0.979 based on n= 800 single values). Lower concordance was reached with amounts of MRD below 0.1%. Comparing data from sample exchange experiments (n = 42 samples; ICC 0.98) and from independent patient cohorts from the four centers (regarding positive samples per time-point of follow-up as well as risk estimates) concordance was also good.

Conclusion:

MRD-evaluation by FCM in ALL can be standardized for reliable multicentric assessment in large trials. © 2008 Clinical Cytometry Society.

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