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Minimal Residual Disease

Monitoring treatment response of childhood precursor B-cell acute lymphoblastic leukemia in the AIEOP-BFM-ALL 2000 protocol with multiparameter flow cytometry: predictive impact of early blast reduction on the remission status after induction

Leukemia volume 23, pages 528–534 (2009)Cite this article

Abstract

Treatment response is a strong outcome predictor for childhood acute lymphoblastic leukemia (ALL). Here, we evaluated the predictive impact of flow cytometric blast quantification assays (absolute blast count, BC, and blast reduction rate, BRR) in peripheral blood (pB) and/or bone marrow (BM) at early time points of induction therapy (days 0, 8 and 15) on the remission status in the AIEOP-BFM-ALL 2000 protocol. At the single parameter level (905 patients), the strongest predictive parameter for the remission status as a dichotomous minimal residual disease (MRD) parameter (positive/negative) has been provided by the BC at day 15 in BM (cutoff: 17 blasts/μl; 50 vs 15%; odds ratio: 5.6; 95% confidence interval: 4.1–7.6, P<0.001), followed by the BRR at day 15 in BM and by the BC at day 8 in pB (odds ratios: 3.8 and 2.6, respectively). In the multiple regression analysis (440 patients), BC in pB (d0 and d8) and in BM (d15) as well as BRR at day 8 in pB provided significantly contributing variables with an overall correct prediction rate of 74.8%. These data show that the quantitative assessment of early response parameters, especially absolute BCs at day 15 in BM, has a predictive impact on the remission status after induction therapy.

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Acknowledgements

We thank all participants and institutions of the AIEOP-BFM-ALL 2000 trial for their close cooperation in providing samples and data from their patients. We are also grateful to M Dunken (Berlin), B Oestereich (Berlin), A Schumich (Vienna), G Froschl (Vienna), Z Husak (Vienna) and O Maglia (Monza) for excellent technical assistance and C Feiler (Berlin) for data management. This work was supported by Wilhelm Sander Stiftung (Grant no. 2004.072.1). Peter Rhein was supported by Deutsche José Carreras Leukämie-Stiftung (Grant no. DJCLS-F05/09). Michael Dworzak was supported by the Austrian National Bank (Grant no. 10962) and Giuseppe Gaipa was supported by Fondazione Tettamanti and Fondazione Cariplo.

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Author notes

  1. G Basso, M Dworzak, G Gaipa and M Veltroni: These authors contributed equally this work.

Authors and Affiliations

  1. Department of Hematology and Oncology, Robert-Roessle-Clinic at HELIOS Klinikum Berlin, Charité-Campus Buch, Germany

    R Ratei, P Rhein, W-D Ludwig & L Karawajew

  2. Department of Pediatrics, Laboratory of Pediatric Onco-Hematology, University Hospital of Padova, Padova, Italy

    G Basso & M Veltroni

  3. Department of Pediatric Hematology and Oncology, Children's Cancer Research Institute and St Anna Children's Hospital Vienna, Vienna, Austria

    M Dworzak

  4. Department of Pediatrics, Tettamanti Research Center, University of Milano-Bicocca, Ospedale San Gerardo, Monza, Italy

    G Gaipa & A Biondi

  5. Department of Pediatrics, University of Florence, Florence, Italy

    M Veltroni

  6. Department of Pediatrics, University Hospital Schleswig-Holstein, Kiel, Germany

    M Schrappe

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  1. R Ratei
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for the AIEOP-BFM-FCM-MRD-Study Group

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Correspondence to R Ratei.

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Ratei, R., Basso, G., Dworzak, M. et al. Monitoring treatment response of childhood precursor B-cell acute lymphoblastic leukemia in the AIEOP-BFM-ALL 2000 protocol with multiparameter flow cytometry: predictive impact of early blast reduction on the remission status after induction. Leukemia 23, 528–534 (2009). https://doi.org/10.1038/leu.2008.324

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