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

Arne Kristian Schwarz (1) , Martin Stanulla (2) , Gunnar Cario (2) , Thomas Flohr (2) , Rosemary Sutton (3) , Anja Möricke (2) , Philippe Anker (4) , Maurice Stroun (4) , Karl Welte (1) , Claus R. Bartram (5) , Martin Schrappe (2) , André Schrauder (2)

1 MHH - Department of Pediatric Hematology and Oncology
2 Department of Pediatrics
3 Children's Cancer Institute Australia
4 Department of Plant Biochemistry and Physiology
5 Institute of Human Genetics

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.

Mots clés: Acute lymphoblastic leukemia; Childhood; Minimal residual disease; Ig/TCR gene rearrangements; Plasma DNA

Arne Kristian Schwarz, Martin Stanulla, Gunnar Cario, Thomas Flohr, Rosemary Sutton, et al.. Quantification of free total plasma DNA and minimal residual disease detection in the plasma of children with acute lymphoblastic leukemia. Annals of Hematology, 2009, 88 (9), pp.897-905. ⟨10.1007/s00277-009-0698-6⟩. ⟨hal-00535029⟩