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Workshop on Minimal Residual Disease

MRD at the end of induction therapy in childhood acute lymphoblastic leukemia: outcome prediction strongly depends on the therapeutic regimen

Leukemia volume 15, pages 283–285 (2001)Cite this article

In childhood acute lymphoblastic leukemia (ALL) about 70% of the patients can be cured with conventional chemotherapy. Despite new chemotherapy strategies, about 30% suffer a relapse. Major approaches for early identification of these patients are: (1) initial features at presentation of the disease (age, leukocyte count, immunophenotype, chromosomal translocations like t(9;22) or t(4;11)); (2) in vivo or in vitro response to chemotherapy or, as recently established: (3) the identification of risk groups via the measurement of minimal residual disease (MRD) during the first 3–5 months of therapy.123 The threshold for predicting relapse depended on the time-point of detection: a high leukemic load of ⩾10−2 residual cells at the end of induction multiplied the risk about 10-fold, about 10−3 distinguished good and poor risk patients at later time-points (eg after 12–15 weeks of therapy). Patients with a high MRD level might benefit from different treatment strategies or bone marrow transplantation. In addition a good molecular responder may be sufficiently treated with a reduced therapeutic regimen.

PCR-based analysis of MRD allows the detection of residual leukemic cells down to a level of 10−5. Due to a high prevalence in B cell precursor (BCP) and T cell leukemias (T-ALL) clonal T cell receptor (TCR) or immunoglobulin heavy or light chain (IgH/IgL) rearrangements were the most suitable targets.45 Patient-specific junctional region sequences served as clone-specific markers in each patient sample.

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Acknowledgements

Part of the data was already presented at the 41st annual meeting of the American Society of Hematology.8 This work was supported by the Fördergemeinschaft Kinderkrebszentrum Hamburg. The authors gratefully acknowledge the participants of the German COALL study: Dr Pongratz (Augsburg); Dr Otte, Dr Jorch (Bielefeld-Bethel); Dr Siegert, Dr Lauterbach (Dresden); PD Dr Beck (Greifswald); Dr Knust (Iserlohn); Dr von Klinggraef (Kiel); Dr Thomas, Dr Völpel (Krefeld); Prof Dr Gutjahr (Mainz); Dr Müller (Mönchengladbach); Dr Klose (München-Harlaching); Prof Dr Drescher (Oldenburg); Dr Helmig (Regensburg); Dr Weber (Wiesbaden); Dr Dohrn (Wuppertal).

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Authors and Affiliations

  1. Department of Pediatric Hematology and Oncology, University of Hamburg, Germany

    U zur Stadt, DO Harms, S Schlüter, G Janka & H Kabisch

  2. Department of Pediatric Hematology and Oncology, University of Hannover, Germany

    M Schrappe

  3. Department of Pediatric Hematology and Oncology, University of Düsseldorf, Germany

    U Goebel

  4. Department of Pediatric Hematology and Oncology, Children's Hospital, Bremen, Germany

    H Spaar

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zur Stadt, U., Harms, D., Schlüter, S. et al. MRD at the end of induction therapy in childhood acute lymphoblastic leukemia: outcome prediction strongly depends on the therapeutic regimen. Leukemia 15, 283–285 (2001). https://doi.org/10.1038/sj.leu.2402019

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