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Prospective use of molecular minimal residual disease for risk stratification in children and adolescents with acute lymphoblastic leukemia

Long-term results of the AIEOP-BFM ALL 2000 trial in Austria

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Summary

Since 1979 Austrian children and adolescents with acute lymphoblastic leukemia (ALL) have been treated according to protocols of the Berlin-Frankfurt-Münster (BFM) study group. The Associazione Italiana di Ematologia e Oncologia Pediatrica and BFM (AIEOP-BFM) ALL 2000 study was designed to prospectively study patient stratification into three risk groups using minimal residual disease (MRD) on two time points during the patient’s early disease course. The MRD levels were monitored by detection of clone-specific rearrangements of the immunoglobulin and T‑cell receptor genes applying a quantitative polymerase chain reaction-based technique. The 7‑year event-free survival (EFS) and overall survival rates for all 608 Austrian patients treated between June 1999 and December 2009 within the AIEOP-BFM 2000 study were 84 ± 2% and 91 ± 1%, respectively, with a median observation time of 6.58 years. Event-free survival for patients with precursor B‑cell and T‑cell ALL were 84 ± 2% (n = 521) and 84 ± 4% (n = 87; p = 0.460), respectively. The MRD assessment was feasible in 94% of the patients and allowed the definition of precursor B‑cell ALL patients with a low, intermediate or high risk of relapse even on top of clinically relevant subgroups. A similar finding with respect to MRD relevance in T‑ALL patients was not possible due to the small number of patients and events. Since this pivotal international AIEOP-BFM ALL 2000 trial, molecular response to treatment has been continuously used with additional refinements to stratify patients into different risk groups in all successive trials of the AIEOP-BFM ALL study group.

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Acknowledgements

We thank all participating institutions, nurses, psychosocial workers and physicians for their support of the study.

Funding

This work was supported by the St. Anna Kinderkrebsforschung (St. Anna Children’s Cancer Research Institute), Austria.

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Authors and Affiliations

  1. Department of Pediatric Hematology and Oncology, St. Anna Children’s Hospital, Medical University of Vienna, Kinderspitalgasse 6, 1090, Vienna, Austria

    Leila Ronceray, Michael Dworzak, Christina Peters, Georg Mann &  Andishe Attarbaschi MD

  2. St. Anna Children’s Cancer Research Institute (CCRI), Vienna, Austria

    Michael Dworzak, Evgenia Glogova, Oskar A. Haas, Karin Nebral, Thomas Lion, Renate Panzer-Grümayer, Sabine Strehl, Ulrike Pötschger, Georg Mann &  Andishe Attarbaschi MD

  3. Department of Radiotherapy, Medical University of Vienna, Vienna, Austria

    Karin Dieckmann

  4. Department of Pediatrics and Adolescent Medicine, Kepler University Hospital Linz, Linz, Austria

    Georg Ebetsberger-Dachs

  5. Labdia Labordiagnostik, Vienna, Austria

    Oskar A. Haas, Karin Nebral & Thomas Lion

  6. Department of Pediatrics and Adolescent Medicine, University Clinics Salzburg, Salzburg, Austria

    Neil Jones

  7. Department of Pediatrics and Adolescent Medicine, State Hospital Leoben, Leoben, Austria

    Reinhard Moser

  8. Department of Pediatrics I, Medical University of Innsbruck, Innsbruck, Austria

    Bernhard Meister

  9. Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria

    Christian Urban

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  1. Leila Ronceray
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the Austrian Berlin-Frankfurt-Münster (BFM) Study Group

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Correspondence to Andishe Attarbaschi MD.

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Conflict of interest

L. Ronceray, M. Dworzak, K. Dieckmann, G. Ebetsberger-Dachs, E. Glogova, O.A. Haas, N. Jones, K. Nebral, R. Moser, T. Lion, B. Meister, R. Panzer-Grümayer, S. Strehl, C. Peters, U. Pötschger, C. Urban, G. Mann and A. Attarbaschi declare that they have no competing interests.

Ethical standards

Institutional review board statement: the AIEOP-BFM ALL 2000 trial in Austria was approved by the institutional ethics committees of the coordinating center in Vienna as well as of all other participating institutions. Informed consent statement: informed consent was obtained from all patients enrolled in the AIEOP-BFM ALL 2000 trial in Austria.

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The authors Georg Mann and Andishe Attarbaschi share senior authorship.

This paper is dedicated to our friend and mentor Helmut Gadner, the former Head of the St. Anna Children Hospital and founder of the Children’s Cancer Research Institute, Vienna, Austria, who chaired the Austrian ALL-BFM Study Group for 30 years and was not only instrumental in conceiving and conducting the Austrian ALL therapy studies, but also to get our clinical and diagnostic achievements internationally recognized.

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Ronceray, L., Dworzak, M., Dieckmann, K. et al. Prospective use of molecular minimal residual disease for risk stratification in children and adolescents with acute lymphoblastic leukemia. Wien Klin Wochenschr (2023). https://doi.org/10.1007/s00508-023-02249-6

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