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Quantification of free total plasma DNA and minimal residual disease detection in the plasma of children with acute lymphoblastic leukemia

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Abstract

The analysis of total plasma DNA and the monitoring of leukemic clone-specific immunoglobulin and/or T-cell receptor gene rearrangements for the evaluation of minimal residual disease (MRD) in the plasma may be useful tools for prognostic purposes or for early detection of subclinical disease recurrence in children with acute lymphoblastic leukemia (ALL). The aim of this paper is to establish reference ranges for total plasma DNA concentrations and to test the feasibility of MRD measurements employing plasma DNA from children with ALL by using real-time quantitative (RQ)-PCR. Despite wide inter-individual variation, the median concentrations of total plasma DNA for 12 healthy donors (57 ng/ml), 21 children with ALL after day 4 of treatment initiation (62 ng/ml) and 13 children with other malignancies (76 ng/ml) were similar. However, ALL patients had significantly higher concentrations at diagnosis (277 ng/ml) and on treatment day 3 (248 ng/ml) before returning to normal afterwards. Early plasma DNA MRD kinetics could be established for 15 ALL patients and showed good concordance with bone marrow MRD. Plasma DNA was higher in children with ALL at diagnosis but returned to normal within the first four treatment days. Despite low concentrations of DNA, it is feasible to measure MRD kinetics in plasma DNA during ALL induction therapy by adapted real-time PCR methodologies.

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Acknowledgments

We acknowledge the cooperation of all patients and their parents, nurses, and physicians who contributed to the collection of samples for this study. We thank Nicole Wittner for expert technical assistance and Dr. Martin Zimmermann for statistical tests and discussion. This work was supported by the Deutsche Krebshilfe (Bonn, Germany) and the Leukemia Research Foundation (Chicago, IL, USA).

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Authors and Affiliations

  1. Department of Pediatric Hematology and Oncology, Hannover Medical School, Hanover, Germany

    Arne Kristian Schwarz & Karl Welte

  2. Department of Pediatrics, University Hospital Schleswig-Holstein, Campus Kiel, Schwanenweg 20, 24105, Kiel, Germany

    Martin Stanulla, Gunnar Cario, Thomas Flohr, Anja Möricke, Martin Schrappe & André Schrauder

  3. Children’s Cancer Institute Australia, Randwick, Australia

    Rosemary Sutton

  4. Department of Plant Biochemistry and Physiology, University of Geneva, Geneva, Switzerland

    Philippe Anker & Maurice Stroun

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

    Claus R. Bartram

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  1. Arne Kristian Schwarz
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  2. Martin Stanulla
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Correspondence to André Schrauder.

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This work was supported by the Deutsche Krebshilfe (Bonn, Germany) and the Leukemia Research Foundation (Chicago, IL, USA).

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Schwarz, A.K., Stanulla, M., Cario, G. et al. Quantification of free total plasma DNA and minimal residual disease detection in the plasma of children with acute lymphoblastic leukemia. Ann Hematol 88, 897–905 (2009). https://doi.org/10.1007/s00277-009-0698-6

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  • DOI: https://doi.org/10.1007/s00277-009-0698-6

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