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Minimal Residual Disease in Childhood ALL and Prognosis

Molecular detection of minimal residual disease is a strong predictive factor of relapse in childhood B-lineage acute lymphoblastic leukemia with medium risk features. A case control study of the International BFM study group

Leukemia volume 14, pages 1939–1943 (2000)Cite this article

Abstract

The medium-risk B cell precursor acute lymphoblastic leukemia (ALL) accounts for 50–60% of total childhood ALL and comprises the largest number of relapses still unpredictable with diagnostic criteria. To evaluate the prognostic impact of minimal residual disease (MRD) in this specific group, a case control study was performed in patients classified and treated as medium (or intermediate)-risk according to the criteria of national studies (ALL-BFM 90, DCLSG protocol ALL-8, AIEOP-ALL 91), which includes a good day 7 treatment response. Standardized polymerase chain reaction (PCR) analysis of patient-specific immunoglobulin and T cell receptor gene (TCR) rearrangements were used as targets for semi-quantitative estimation of MRD levels: ⩾10−2, 10−3, ⩽10−4. Twenty-nine relapsing ALL patients were matched with the same number of controls by using white blood cell count (WBC), age, sex, and time in first complete remission, as matching factors. MRD was evaluated at time-point 1 (end of protocol Ia of induction treatment, ie 6 weeks from diagnosis) and time-point 2 (before consolidation treatment, ie 3 months from diagnosis). MRD-based high risk patients (⩾10−3 at both time-points) were more frequently present in the relapsed cases than in controls (14 vs 2), while MRD-based low risk patients (MRD negative at both time-points) (1 vs 18) showed the opposite distribution. MRD-based high risk cases experienced a significantly higher relapse rate than all other patients, according to the estimated seven-fold increase in the odds of failure, and a much higher rate than MRD-based low risk patients (OR = 35.7; P = 0.003). Using the Cox model, the prediction of the relapse-free interval at 4 years was 44.7%, 76.4% and 97.7% according to the different MRD categories. MRD-based risk group classification demonstrate their clinical relevance within the medium-risk B cell precursor ALL which account for the largest number of unpredictable relapses, despite the current knowledge about clinical and biological characteristics at diagnosis. Therefore, MRD detection during the first 3 months of follow-up can provide the tools to target more intensive therapy to those patients at true risk of relapse.

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Acknowledgements

This work was supported by Fondazione M Tettamanti, Associazione Italiana per la Ricerca sul Cancro (AIRC) and MURST 40% (AB, ED'A and GM); by a grant from the Deutsche Krebshilfe (to CRB); by the Osterreichische Kinderkrebshilfe (ERP-G and KF), by a grant from the FWF No. P 13575-MED (to ERP-G); by Dutch Cancer Society (Koningin Wilhelmina Fonds), grant EUR 94-852 (MJW and JJMvD).

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Authors and Affiliations

  1. Clinica Pediatrica Università di Milano-Bicocca, Ospedale S Gerardo, Monza, Italy

    A Biondi, E D'Aniello & A Pannunzio

  2. Department of Medicine and Public Health, Università di Verona, Italy

    MG Valsecchi

  3. Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany

    T Seriu, M Schrappe & CR Bartram

  4. Department of Immunology, Erasmus University Rotterdam, Rotterdam, The Netherlands

    MJ Willemse & JJM van Dongen

  5. Children's Cancer Research Institute, St Anna Kinderspital, Vienna, Austria

    K Fasching, H Gadner & ER Panzer-Grümayer

  6. Dutch Childhood Leukemia Study Group (DCLSG), The Hague, The Netherlands

    WA Kamps

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Biondi, A., Valsecchi, M., Seriu, T. et al. Molecular detection of minimal residual disease is a strong predictive factor of relapse in childhood B-lineage acute lymphoblastic leukemia with medium risk features. A case control study of the International BFM study group. Leukemia 14, 1939–1943 (2000). https://doi.org/10.1038/sj.leu.2401922

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